InternalMed_Harrison

InternalMed_Harrison. they are tested for these infections, however, they should receive the same regimen given to the male index case. Patients with confirmed persistence or recurrence of urethritis after treatment should be re-treated with the initial regimen if they did not comply with the original treatment or were reexposed to an untreated partner. Otherwise, an intraurethral swab specimen and a first-voided urine sample should be tested for T. vaginalis (currently done by culture, although NAATs are more sensitive and are approved for the diagnosis of trichomoniasis in women). If compliance with initial treatment is confirmed and reexposure to an untreated sex partner is deemed unlikely, the recommended treatment is with metronidazole or tinidazole (2 g by mouth in a single dose) plus azithromycin (1 g by mouth in a single dose); the azithromycin component is especially important if this drug has not been given during initial therapy.


InternalMed_Harrison

InternalMed_Harrison. Acute epididymitis, almost always unilateral, produces pain, swelling, and tenderness of the epididymis, with or without symptoms or signs of urethritis. This condition must be differentiated from testicular torsion, tumor, and trauma. Torsion, a surgical emergency, usually occurs in Sexually Transmitted Infections: Overview and Clinical Approach Chlamydia trachomatis Demonstration of urethral discharge or pyuria Exclusion of local or systemic Urethral Gram’s stain to confirm urethritis, detect gram-negative Herpes simplex virus diplococci Test for N. gonorrhoeae, C. trachomatis (unless excluded): Ceftriaxone, 250 mg IMa plus Azithromycin, 1 g PO Management of Recurrence Confirm objective evidence of urethritis. If patient was reexposed to untreated or new partner, repeat treatment of patient and partner.


InternalMed_Harrison

InternalMed_Harrison. Azithromycin, 1 g PO Management of Recurrence Confirm objective evidence of urethritis. If patient was reexposed to untreated or new partner, repeat treatment of patient and partner. If patient was not reexposed, consider infection with T. vaginalisb or doxycycline-resistant M. genitaliumc or Ureaplasma, and consider treatment with metronidazole, azithromycin, or both.


InternalMed_Harrison

InternalMed_Harrison. aNeither oral cephalosporins nor fluoroquinolones are recommended for treatment of gonorrhea in the United States because of the emergence of increasing fluoroquinolone resistance in N. gonorrhoeae, especially (but not only) among men who have sex with men, and decreasing susceptibility of a still-small proportion of gonococci to ceftriaxone (Fig. 163-1). Updates on the emergence of antimicrobial resistance in N. gonorrhoeae can be obtained from the Centers for Disease Control and Prevention at http://www.cdc.gov/std. bIn men, the diagnosis of T. vaginalis infection requires culture, DNA testing, or nucleic acid amplification testing (where available) of early-morning first-voided urine sediment or of a urethral swab specimen obtained before voiding. cM. genitalium is often resistant to doxycycline and azithromycin but is usually susceptible to the fluoroquinolone moxifloxacin. Until nucleic acid amplification testing for M. genitalium becomes commercially available, moxifloxacin can


InternalMed_Harrison

InternalMed_Harrison. and azithromycin but is usually susceptible to the fluoroquinolone moxifloxacin. Until nucleic acid amplification testing for M. genitalium becomes commercially available, moxifloxacin can be considered for treatment of refractory nongonococcal, nonchlamydial urethritis.


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InternalMed_Harrison. the second or third decade of life and produces a sudden onset of pain, elevation of the testicle within the scrotal sac, rotation of the epididymis from a posterior to an anterior position, and absence of blood flow on Doppler examination or 99mTc scan. Persistence of symptoms after a course of therapy for epididymitis suggests the possibility of testicular tumor or of a chronic granulomatous disease, such as tuberculosis. In sexually active men under age 35, acute epididymitis is caused most frequently by C. trachomatis and less commonly by N. gonorrhoeae and is usually associated with overt or subclinical urethritis. Acute epididymitis occurring in older men or following urinary tract instrumentation is usually caused by urinary pathogens. Similarly, epididymitis in men who have practiced insertive rectal intercourse is often caused by Enterobacteriaceae. These older men usually have no urethritis but do have bacteriuria.


InternalMed_Harrison

InternalMed_Harrison. Ceftriaxone (250 mg as a single dose IM) followed by doxycycline (100 mg by mouth twice daily for 10 days) constitutes effective treatment for epididymitis caused by N. gonorrhoeae or C. trachomatis. Neither oral cephalosporins nor fluoroquinolones are recommended for treatment of gonorrhea in the United States because of resistance in N. gonorrhoeae, especially (but not only) among MSM (Fig. 163-1). Oral levofloxacin (500 mg once daily for 10 days) is also effective for syndrome-based initial treatment of epididymitis when infection with Enterobacteriaceae is suspected; however, this regimen should be combined with effective therapy for possible gonococcal or chlamydial infection unless bacteriuria with Enterobacteriaceae is confirmed.


InternalMed_Harrison

InternalMed_Harrison. C. trachomatis, N. gonorrhoeae, and occasionally HSV cause symptomatic urethritis—known as the urethral syndrome in women—that is characterized by “internal” dysuria (usually without urinary urgency or frequency), pyuria, and an absence of Escherichia coli and other Percentage of isolates 1 0.8 0.6 0.4 0.2 FIGURE 163-1 Proportion of Neisseria gonorrhoeae isolates with elevated ceftriaxone minimum inhibitory concentrations (MICs), United States 2008–2012. Elevated resistance is defined by ceftriaxone MICs of ≥0.125 μg/mL. *Preliminary (January–June).


InternalMed_Harrison

InternalMed_Harrison. (From the Centers for Disease Control and Prevention: Gonococcal Isolate Surveillance Project [GISP], 2013.) uropathogens at counts of ≥102/mL in urine. In contrast, the dysuria associated with vulvar herpes or vulvovaginal candidiasis (and perhaps with trichomoniasis) is often described as “external,” being caused by painful contact of urine with the inflamed or ulcerated labia or introitus. Acute onset, association with urinary urgency or frequency, hematuria, or suprapubic bladder tenderness suggests bacterial cystitis. Among women with symptoms of acute bacterial cystitis, costovertebral pain and tenderness or fever suggests acute pyelonephritis. The management of bacterial urinary tract infection (UTI) is discussed in Chap. 162.


InternalMed_Harrison

InternalMed_Harrison. Signs of vulvovaginitis, coupled with symptoms of external dysuria, suggest vulvar infection (e.g., with HSV or Candida albicans). Among dysuric women without signs of vulvovaginitis, bacterial UTI must be differentiated from the urethral syndrome by assessment of risk, evaluation of the pattern of symptoms and signs, and specific microbiologic testing. An STI etiology of the urethral syndrome is suggested by young age, more than one current sexual partner, a new partner within the past month, a partner with urethritis, or coexisting mucopurulent cervicitis (see below). The finding of a single urinary pathogen, such as E. coli or Staphylococcus saprophyticus, at a concentration of ≥102/mL in a properly collected specimen of midstream urine from a dysuric woman with pyuria indicates probable bacterial UTI, whereas pyuria with <102 conventional uropathogens per milliliter of urine (“sterile” pyuria) suggests acute urethral syndrome due to C. trachomatis or


InternalMed_Harrison

InternalMed_Harrison. N. gonorrhoeae. Gonorrhea and chlamydial infection should be sought by specific tests (e.g., NAATs of vaginal secretions collected with a swab). Among dysuric women with sterile pyuria caused by infection with N. gonorrhoeae or C. trachomatis, appropriate treatment alleviates dysuria. The role of M. genitalium in the urethral syndrome in women remains undefined. VULVOVAGINAL INFECTIONS Abnormal Vaginal Discharge If directly questioned about vaginal discharge during routine health checkups, many women acknowledge having nonspecific symptoms of vaginal discharge that do not correlate with objective signs of inflammation or with actual infection. However, unsolicited reporting of abnormal vaginal discharge does suggest bacterial vaginosis or trichomoniasis. Specifically, an abnormally increased amount or an abnormal odor of the discharge is associated with one or both of these conditions. Cervical infection with N. gonorrhoeae or


InternalMed_Harrison

InternalMed_Harrison. C. trachomatis does not often cause an increased amount or abnormal odor of discharge; however, when these pathogens cause cervicitis, they—like T. vaginalis—often result in an increased number of neutrophils in vaginal fluid, which thus takes on a yellow color. Vulvar conditions such as genital herpes or vulvovaginal candidiasis can cause vulvar pruritus, burning, irritation, or lesions as well as external dysuria (as urine passes over the inflamed vulva or areas of epithelial disruption) or vulvar dyspareunia.


InternalMed_Harrison

InternalMed_Harrison. Certain vulvovaginal infections may have serious sequelae. Trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis have all been associated with increased risk of acquisition of HIV infection; bacterial vaginosis may promote HIV transmission from HIV-infected women to their male sex partners. Vaginal trichomoniasis and bacterial vaginosis early in pregnancy independently predict premature onset of labor. Bacterial vaginosis can also lead to anaerobic bacterial infection of the endometrium and salpinges. Vaginitis may be an early and prominent feature of toxic shock syndrome, and recurrent or chronic vulvovaginal candidiasis develops with increased frequency among women who have systemic illnesses, such as diabetes mellitus or HIV-related immunosuppression (although only a very small proportion of women with recurrent vulvovaginal candidiasis in industrialized countries actually have a serious predisposing illness).


InternalMed_Harrison

InternalMed_Harrison. Thus vulvovaginal symptoms or signs warrant careful evaluation, including speculum and pelvic examination, simple rapid diagnostic tests, and appropriate therapy specific for the anatomic site and type of infection. Unfortunately, a survey in the United States indicated that clinicians seldom perform the tests required to establish the cause of such symptoms. Further, comparison of telephone and office management of vulvovaginal symptoms has documented the inaccuracy of the former, and comparison of evaluations by nurse-midwives with those by physician-practitioners showed that the practitioners’ clinical evaluations correlated poorly both with the nurses’ evalua-873 tions and with diagnostic tests. The diagnosis and treatment of the three most common types of vaginal infection are summarized in Table 163-5.


InternalMed_Harrison

InternalMed_Harrison. Inspection of the vulva and perineum may reveal tender genital ulcerations or fissures (typically due to HSV infection or vulvovaginal candidiasis) or discharge visible at the introitus before insertion of a speculum (suggestive of bacterial vaginosis or trichomoniasis). Speculum examination permits the clinician to discern whether the discharge in fact looks abnormal and whether any abnormal discharge in the vagina emanates from the cervical os (mucoid and, if abnormal, yellow) or from the vagina (not mucoid, since the vaginal epithelium does not produce mucus). Symptoms or signs of abnormal vaginal discharge should prompt testing of vaginal fluid for pH, for a fishy odor when mixed with 10% KOH, and for certain microscopic features when mixed with saline (motile trichomonads and/or “clue cells”) and with 10% KOH (pseudohyphae or hyphae indicative of vulvovaginal candidiasis). Additional objective laboratory tests useful for establishing the cause of abnormal vaginal discharge


InternalMed_Harrison

InternalMed_Harrison. “clue cells”) and with 10% KOH (pseudohyphae or hyphae indicative of vulvovaginal candidiasis). Additional objective laboratory tests useful for establishing the cause of abnormal vaginal discharge include rapid point-ofcare tests for bacterial vaginosis and T. vaginalis, as described below; a DNA probe test (the Affirm test) to detect T. vaginalis and C. albicans as well as the increased concentrations of Gardnerella vaginalis associated with bacterial vaginosis; and a NAAT for T. vaginalis. Gram’s


InternalMed_Harrison

InternalMed_Harrison. Sexually Transmitted Infections: Overview and Clinical Approach aColor of discharge is best determined by examination against the white background of a swab. bA pH determination is not useful if blood is present or if the test is performed on endocervical secretions. cTo detect fungal elements, vaginal fluid is digested with 10% KOH prior to microscopic examination; to examine for other features, fluid is mixed (1:1) with physiologic saline. Gram’s stain is also excellent for detecting yeasts (less predictive of vulvovaginitis) and pseudomycelia or mycelia (strongly predictive of vulvovaginitis) and for distinguishing normal flora from the mixed flora seen in bacterial vaginosis, but it is less sensitive than the saline preparation for detection of T. vaginalis. dNAAT, nucleic acid amplification test (where available).


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InternalMed_Harrison. 874 staining of vaginal fluid can be used to score alterations in the vaginal microbiota but is used primarily for research purposes and requires familiarity with the morphotypes and scale involved.


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InternalMed_Harrison. Patterns of treatment for vaginal discharge vary widely. In developing countries, where clinics or pharmacies often dispense treatment based on symptoms alone without examination or testing, oral treatment with metronidazole—particularly with a 7-day regimen— provides reasonable coverage against both trichomoniasis and bacterial vaginosis, the usual causes of symptoms of vaginal discharge. Metronidazole treatment of sex partners prevents reinfection of women with trichomoniasis, even though it does not help prevent the recurrence of bacterial vaginosis. Guidelines for syndromic management promulgated by the World Health Organization suggest consideration of treatment for cervical infection and for trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis in women with symptoms of abnormal vaginal discharge. However, it is important to note that the majority of chlamydial and gonococcal cervical infections produce no symptoms.


InternalMed_Harrison

InternalMed_Harrison. In industrialized countries, clinicians treating symptoms and signs of abnormal vaginal discharge should, at a minimum, differentiate between bacterial vaginosis and trichomoniasis, because optimal management of patients and partners differs for these two conditions (as discussed briefly below).


InternalMed_Harrison

InternalMed_Harrison. Vaginal Trichomoniasis (See also Chap. 254) Symptomatic trichomoniasis characteristically produces a profuse, yellow, purulent, homogeneous vaginal discharge and vulvar irritation, sometimes with visible inflammation of the vaginal and vulvar epithelium and petechial lesions on the cervix (the so-called strawberry cervix, usually evident only by colposcopy). The pH of vaginal fluid—normally <4.7—usually rises to ≥5. In women with typical symptoms and signs of trichomoniasis, microscopic examination of vaginal discharge mixed with saline reveals motile trichomonads in most culture-positive cases. However, saline microscopy probably detects only one-half of all cases, and, especially in the absence of symptoms or signs, culture or NAAT is usually required for detection of the organism. NAAT for T. vaginalis is as sensitive as or more sensitive than culture, and NAAT of urine has disclosed surprisingly high prevalences of this pathogen among men at several STD clinics in the United


InternalMed_Harrison

InternalMed_Harrison. NAAT for T. vaginalis is as sensitive as or more sensitive than culture, and NAAT of urine has disclosed surprisingly high prevalences of this pathogen among men at several STD clinics in the United States. Treatment of asymptomatic as well as symptomatic cases reduces rates of transmission and prevents later development of symptoms.


InternalMed_Harrison

InternalMed_Harrison. Only nitroimidazoles (e.g., metronidazole and tinidazole) consistently cure trichomoniasis. A single 2-g oral dose of metronidazole is effective and much less expensive than the alternatives. Tinidazole has a longer half-life than metronidazole, causes fewer gastrointestinal symptoms, and may be useful in treating trichomoniasis that fails to respond to metronidazole. Treatment of sexual partners— facilitated by dispensing metronidazole to the female patient to give to her partner(s), with a warning about avoiding the concurrent use of alcohol—significantly reduces both the risk of reinfection and the reservoir of infection; treating the partner is the standard of care. Intravaginal treatment with 0.75% metronidazole gel is not reliable for vaginal trichomoniasis. Systemic use of metronidazole is recommended throughout pregnancy. In a large randomized trial, metronidazole treatment of trichomoniasis during pregnancy did not reduce—and in fact actually increased—the frequency of


InternalMed_Harrison

InternalMed_Harrison. is recommended throughout pregnancy. In a large randomized trial, metronidazole treatment of trichomoniasis during pregnancy did not reduce—and in fact actually increased—the frequency of perinatal morbidity; thus routine screening of asymptomatic pregnant women for trichomoniasis is not recommended.


InternalMed_Harrison

InternalMed_Harrison. Bacterial Vaginosis Bacterial vaginosis (formerly termed nonspecific vaginitis, Haemophilus vaginitis, anaerobic vaginitis, or Gardnerella-associated vaginal discharge) is a syndrome of complex etiology that is characterized by symptoms of vaginal malodor and a slightly to moderately increased white discharge, which appears homogeneous, is low in viscosity, and evenly coats the vaginal mucosa. Bacterial vaginosis has been associated with increased risk of acquiring several other genital infections, including those caused by HIV, C. trachomatis, and N. gonorrhoeae. Other risk factors include recent unprotected vaginal intercourse, having a female sex partner, and vaginal douching. Although bacteria associated with bacterial vaginosis have been detected under the foreskin of uncircumcised men, metronidazole treatment of male partners has not reduced the rate of recurrence among affected women.


InternalMed_Harrison

InternalMed_Harrison. Among women with bacterial vaginosis, culture of vaginal fluid has shown markedly increased prevalences and concentrations of


InternalMed_Harrison

InternalMed_Harrison. G. vaginalis, Mycoplasma hominis, and several anaerobic bacteria (e.g., Mobiluncus, Prevotella [formerly Bacteroides], and some Peptostreptococcus species) as well as an absence of hydrogen peroxide– producing Lactobacillus species that constitute most of the normal vaginal microbiota and help protect against certain cervical and vaginal infections. Broad-range polymerase chain reaction (PCR) amplification of 16S rDNA in vaginal fluid, with subsequent identification of specific bacterial species by various methods, has documented an even greater and unexpected bacterial diversity, including several unique species not previously cultivated (e.g., three species in the order Clostridiales that appear to be specific for bacterial vaginosis and are associated with metronidazole treatment failure [Fig. 163-2]). Also detected are DNA sequences related to Atopobium vaginae, an organism that is strongly associated with bacterial vaginosis, is resistant to metronidazole, and is also associated


InternalMed_Harrison

InternalMed_Harrison. [Fig. 163-2]). Also detected are DNA sequences related to Atopobium vaginae, an organism that is strongly associated with bacterial vaginosis, is resistant to metronidazole, and is also associated with recurrent bacterial vaginosis after metronidazole treatment. Other genera newly implicated in bacterial vaginosis include Megasphaera, Leptotrichia, Eggerthella, and Dialister.


InternalMed_Harrison

InternalMed_Harrison. Bacterial vaginosis is conventionally diagnosed clinically with the Amsel criteria, which include any three of the following four clinical abnormalities: (1) objective signs of increased white homogeneous vaginal discharge; (2) a vaginal discharge pH of >4.5; (3) liberation of a distinct fishy odor (attributable to volatile amines such as trimethylamine) immediately after vaginal secretions are mixed with a 10% solution of KOH; and (4) microscopic demonstration of “clue cells” (vaginal epithelial cells coated with coccobacillary organisms, which have a granular appearance and indistinct borders; Fig. 163-3) on a wet mount prepared by mixing vaginal secretions with normal saline in a ratio of ~1:1.


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InternalMed_Harrison. FIGURE 163-2 Broad-range polymerase chain reaction amplification of 16S rDNA in vaginal fluid from a woman with bacterial vaginosis shows a field of bacteria hybridizing with probes for bacterial vaginosis– associated bacterium 1 (BVAB-1, visible as a thin, curved green rod) and for BVAB-2 (red). The inset shows that BVAB-1 has a morphology similar to that of Mobiluncus (curved rod). (Reprinted with permission from DN Fredricks et al: N Engl J Med 353:1899, 2005.) FIGURE 163-3 Wet mount of vaginal fluid showing typical clue cells from a woman with bacterial vaginosis. Note the obscured epithelial cell margins and the granular appearance attributable to many adherent bacteria (×400). (Photograph provided by Lorna K. Rabe, reprinted with permission from S Hillier et al, in KK Holmes et al [eds]: Sexually Transmitted Diseases, 4th ed. New York, McGraw-Hill, 2008.)


InternalMed_Harrison

InternalMed_Harrison. The standard dosage of oral metronidazole for the treatment of bacterial vaginosis is 500 mg twice daily for 7 days. The single 2-g oral dose of metronidazole recommended for trichomoniasis produces significantly lower short-term cure rates and should not be used. Intravaginal treatment with 2% clindamycin cream (one full applicator [5 g containing 100 mg of clindamycin phosphate] each night for 7 nights) or with 0.75% metronidazole gel (one full applicator [5 g containing 37.5 mg of metronidazole] twice daily for 5 days) is also approved for use in the United States and does not elicit systemic adverse reactions; the response to both of these treatments is similar to the response to oral metronidazole. Other alternatives include oral clindamycin (300 mg twice daily for 7 days), clindamycin ovules (100 g intravaginally once at bedtime for 3 days), and oral tinidazole (1 g daily for 5 days or 2 g daily for 3 days). Unfortunately, recurrence over the long term (i.e., several months


InternalMed_Harrison

InternalMed_Harrison. ovules (100 g intravaginally once at bedtime for 3 days), and oral tinidazole (1 g daily for 5 days or 2 g daily for 3 days). Unfortunately, recurrence over the long term (i.e., several months later) is distressingly common after either oral or intravaginal treatment. A randomized trial comparing intravaginal gel containing 37.5 mg of metronidazole with a suppository containing 500 mg of metronidazole plus nystatin (the latter not marketed in the United States) showed significantly higher rates of recurrence with the 37.5-mg regimen; this result suggests that higher metronidazole dosages may be important in topical intravaginal therapy. Recurrences can be significantly lessened with the twice-weekly use of suppressive intravaginal metronidazole gel. As stated above, treatment of male partners with metronidazole does not prevent recurrence of bacterial vaginosis.


InternalMed_Harrison

InternalMed_Harrison. Efforts to replenish numbers of vaginal lactobacilli that produce hydrogen peroxide and probably sustain vaginal health have been unsuccessful. While one randomized trial of orally ingested lactobacilli found reduced rates of recurrent bacterial vaginosis, this result has not yet been either confirmed or refuted, and a randomized multicenter trial in the United States found no benefit of repeated intravaginal inoculation of a vaginal peroxide-producing Lactobacillus species following treatment of bacterial vaginosis with metronidazole. A meta-analysis of 18 studies concluded that bacterial vaginosis during pregnancy substantially increased the risk of preterm delivery and of spontaneous abortion. However, most studies of topical intravaginal treatment of bacterial vaginosis with clindamycin during pregnancy have not reduced adverse pregnancy outcomes. Numerous trials of oral metronidazole treatment during pregnancy have given inconsistent results, and a 2013 Cochrane review concluded


InternalMed_Harrison

InternalMed_Harrison. during pregnancy have not reduced adverse pregnancy outcomes. Numerous trials of oral metronidazole treatment during pregnancy have given inconsistent results, and a 2013 Cochrane review concluded that antenatal treatment of women with bacterial vaginosis—even those with previous preterm deliv-875 ery—did not reduce the risk of preterm delivery. The U.S. Preventive Services Task Force thus recommends against routine screening of pregnant women for bacterial vaginosis.


InternalMed_Harrison

InternalMed_Harrison. Vulvovaginal Pruritus, Burning, or Irritation Vulvovaginal candidiasis produces vulvar pruritus, burning, or irritation, generally without symptoms of increased vaginal discharge or malodor. Genital herpes can produce similar symptoms, with lesions sometimes difficult to distinguish from the fissures and inflammation caused by candidiasis. Signs of vulvovaginal candidiasis include vulvar erythema, edema, fissures, and tenderness. With candidiasis, a white scanty vaginal discharge sometimes takes the form of white thrush-like plaques or cottage cheese–like curds adhering loosely to the vaginal epithelium. C. albicans accounts for nearly all cases of symptomatic vulvovaginal candidiasis, which probably arise from endogenous strains of C. albicans that have colonized the vagina or the intestinal tract. Complicated vulvovaginal candidiasis includes cases that recur four or more times per year; are unusually severe; are caused by non-albicans Candida species; or occur in women with


InternalMed_Harrison

InternalMed_Harrison. intestinal tract. Complicated vulvovaginal candidiasis includes cases that recur four or more times per year; are unusually severe; are caused by non-albicans Candida species; or occur in women with uncontrolled diabetes, debilitation, immunosuppression, or pregnancy.


InternalMed_Harrison

InternalMed_Harrison. In addition to compatible clinical symptoms, the diagnosis of vulvovaginal candidiasis usually involves the demonstration of pseudohyphae or hyphae by microscopic examination of vaginal fluid mixed with saline or 10% KOH or subjected to Gram’s staining. Microscopic examination is less sensitive than culture but correlates better with symptoms. Culture is typically reserved for cases that do not respond to standard first-line antimycotic agents and is undertaken to rule out imidazole or azole resistance (often associated with Candida glabrata) or before the initiation of suppressive antifungal therapy for recurrent disease. TREATMEnT VulVoVAgInAl PrurITus, burnIng, or IrrITATIon


InternalMed_Harrison

InternalMed_Harrison. Symptoms and signs of vulvovaginal candidiasis warrant treatment, usually intravaginal administration of any of several imidazole antibiotics (e.g., miconazole or clotrimazole) for 3–7 days or of a single dose of oral fluconazole (Table 163-5). Over-the-counter marketing of such preparations has reduced the cost of care and made treatment more convenient for many women with recurrent yeast vulvovaginitis. However, most women who purchase these preparations do not have vulvovaginal candidiasis, whereas many do have other vaginal infections that require different treatment. Therefore, only women with classic symptoms of vulvar pruritus and a history of previous episodes of yeast vulvovaginitis documented by an experienced clinician should self-treat. Short-course topical intravaginal azole drugs are effective for the treatment of uncomplicated vulvovaginal candidiasis (e.g., clotrimazole, two 100-mg vaginal tablets daily for 3 days; or miconazole, a 1200-mg vaginal suppository as a


InternalMed_Harrison

InternalMed_Harrison. drugs are effective for the treatment of uncomplicated vulvovaginal candidiasis (e.g., clotrimazole, two 100-mg vaginal tablets daily for 3 days; or miconazole, a 1200-mg vaginal suppository as a single dose). Single-dose oral treatment with fluconazole (150 mg) is also effective and is preferred by many patients. Management of complicated cases (see above) and those that do not respond to the usual intravaginal or single-dose oral therapy often involves prolonged or periodic oral therapy; this situation is discussed extensively in the 2010 CDC STD treatment guidelines (http://www.cdc.gov/std/treatment). Treatment of sexual partners is not routinely indicated.


InternalMed_Harrison

InternalMed_Harrison. Other Causes of Vaginal Discharge or Vaginitis In the ulcerative vaginitis associated with staphylococcal toxic shock syndrome, Staphylococcus aureus should be promptly identified in vaginal fluid by Gram’s stain and by culture. In desquamative inflammatory vaginitis, smears of vaginal fluid reveal neutrophils, massive vaginal epithelial-cell exfoliation with increased numbers of parabasal cells, and gram-positive cocci; this syndrome may respond to treatment with 2% clindamycin cream, often given in combination with topical steroid preparations for several weeks. Additional causes


InternalMed_Harrison

InternalMed_Harrison. Sexually Transmitted Infections: Overview and Clinical Approach 876 of vaginitis and vulvovaginal symptoms include retained foreign bodies (e.g., tampons), cervical caps, vaginal spermicides, vaginal antiseptic preparations or douches, vaginal epithelial atrophy (in postmenopausal women or during prolonged breast-feeding in the postpartum period), allergic reactions to latex condoms, vaginal aphthae associated with HIV infection or Behçet’s syndrome, and vestibulitis (a poorly understood syndrome).


InternalMed_Harrison

InternalMed_Harrison. Mucopurulent cervicitis (MPC) refers to inflammation of the columnar epithelium and subepithelium of the endocervix and of any contiguous columnar epithelium that lies exposed in an ectopic position on the ectocervix. MPC in women represents the “silent partner” of urethritis in men, being equally common and often caused by the same agents (N. gonorrhoeae, C. trachomatis, or—as shown by case–control studies—M. genitalium); however, MPC is more difficult than urethritis to recognize. As the most common manifestation of these serious bacterial infections in women, MPC can be a harbinger or sign of upper genital tract infection, also known as pelvic inflammatory disease (PID; see below). In pregnant women, MPC can lead to obstetric complications. In a prospective study in Seattle of 167 consecutive patients with MPC (defined on the basis of yellow endocervical mucopus or ≥30 polymorphonuclear leukocytes [PMNs]/1000× microscopic field) who were seen at STD clinics during the 1980s,


InternalMed_Harrison

InternalMed_Harrison. consecutive patients with MPC (defined on the basis of yellow endocervical mucopus or ≥30 polymorphonuclear leukocytes [PMNs]/1000× microscopic field) who were seen at STD clinics during the 1980s, slightly more than one-third of cervicovaginal specimens tested for C. trachomatis,


InternalMed_Harrison

InternalMed_Harrison. N. gonorrhoeae, M. genitalium, HSV, and T. vaginalis revealed no identifiable etiology (Fig. 163-4). More recently, a study in Baltimore using NAATs for these pathogens still failed to identify a microbiologic etiology in nearly one-half of the 133 women with MPC.


InternalMed_Harrison

InternalMed_Harrison. The diagnosis of MPC rests on the detection of cardinal signs at the cervix, including yellow mucopurulent discharge from the cervical os, endocervical bleeding upon gentle swabbing, and edematous cervical ectopy (see below); the latter two findings are somewhat more common with MPC due to chlamydial infection, but signs alone do not allow a distinction between the causative pathogens. Unlike the endocervicitis produced by gonococcal or chlamydial infection, cervicitis caused by HSV produces ulcerative lesions on the stratified squamous epithelium of the ectocervix as well as on the columnar epithelium. Yellow cervical mucus on a white swab removed from the endocervix indicates the presence of PMNs. Gram’s staining may confirm their


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InternalMed_Harrison. No organism 35% CT 17% GC 13% TV 10% MG 8% HSV 5% MG/CT 2% MG/GC/CT 1% GC/CT 7% FIGURE 163-4 Organisms detected among female sexually transmitted disease clinic patients with mucopurulent cervicitis (n = 167). CT, Chlamydia trachomatis; GC, gonococcus; MG, Mycoplasma genitalium; TV, Trichomonas vaginalis; HSV, herpes simplex virus. (Courtesy of Dr. Lisa Manhart; with permission.) presence, although it adds relatively little to the diagnostic value of assessment for cervical signs. The presence of ≥20 PMNs/1000× microscopic field within strands of cervical mucus not contaminated by vaginal squamous epithelial cells or vaginal bacteria indicates endocervicitis. Detection of intracellular gram-negative diplococci in carefully collected endocervical mucus is quite specific but ≤50% sensitive for gonorrhea. Therefore, specific and sensitive tests for N. gonorrhoeae as well as for C. trachomatis (e.g., NAATs) are always indicated in the evaluation of MPC.


InternalMed_Harrison

InternalMed_Harrison. Although the above criteria for MPC are neither highly specific nor highly predictive of gonococcal or chlamydial infection in some settings, the 2010 CDC STD guidelines call for consideration of empirical treatment for MPC, pending test results, in most patients. Presumptive treatment with antibiotics active against C. trachomatis should be provided for women at increased risk for this common STI (risk factors: age <25 years, new or multiple sex partners, and unprotected sex), especially if follow-up cannot be ensured. Concurrent therapy for gonorrhea is indicated if the prevalence of this infection is substantial in the relevant patient population (e.g., young adults, a clinic with documented high prevalence). In this situation, therapy should include a single-dose regimen effective for gonorrhea plus treatment for chlamydial infection, as outlined in Table 163-4 for the treatment of urethritis. In settings where gonorrhea is much less common than chlamydial infection, initial


InternalMed_Harrison

InternalMed_Harrison. for gonorrhea plus treatment for chlamydial infection, as outlined in Table 163-4 for the treatment of urethritis. In settings where gonorrhea is much less common than chlamydial infection, initial therapy for chlamydial infection alone suffices, pending test results for gonorrhea. The etiology and potential benefit of treatment for endocervicitis not associated with gonorrhea or chlamydial infection have not been established. Although the antimicrobial susceptibility of


InternalMed_Harrison

InternalMed_Harrison. M. genitalium is not yet well defined, the organism frequently persists after doxycycline therapy, and it currently seems reasonable to use azithromycin to treat possible M. genitalium infection in such cases. With resistance of M. genitalium to azithromycin now recognized, moxifloxacin may be a reasonable alternative. The sexual partner(s) of a woman with MPC should be examined and given a regimen similar to that chosen for the woman unless results of tests for gonorrhea or chlamydial infection in either partner warrant different therapy or no therapy.


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InternalMed_Harrison. Cervical ectopy, often mislabeled “cervical erosion,” is easily confused with infectious endocervicitis. Ectopy represents the presence of the one-cell-thick columnar epithelium extending from the endocervix out onto the visible ectocervix. In ectopy, the cervical os may contain clear or slightly cloudy mucus but usually not yellow mucopus. Colposcopy shows intact epithelium. Normally found during adolescence and early adulthood, ectopy gradually recedes through the second and third decades of life, as squamous metaplasia replaces the ectopic columnar epithelium. Oral contraceptive use favors the persistence or reappearance of ectopy, while smoking apparently accelerates squamous metaplasia. Cauterization of ectopy is not warranted. Ectopy may render the cervix more susceptible to infection with N. gonorrhoeae, C. trachomatis, or HIV.


InternalMed_Harrison

InternalMed_Harrison. The term pelvic inflammatory disease usually refers to infection that ascends from the cervix or vagina to involve the endometrium and/ or fallopian tubes. Infection can extend beyond the reproductive tract to cause pelvic peritonitis, generalized peritonitis, perihepatitis, perisplenitis, or pelvic abscess. Rarely, infection not related to specific sexually transmitted pathogens extends secondarily to the pelvic organs (1) from adjacent foci of inflammation (e.g., appendicitis, regional ileitis, or diverticulitis) or bacterial vaginosis, (2) as a result of hematogenous dissemination (e.g., of tuberculosis or staphylococcal bacteremia), or (3) as a complication of certain tropical diseases (e.g., schistosomiasis). Intrauterine infection can be primary (spontaneously occurring and usually sexually transmitted) or secondary to invasive intrauterine surgical procedures (e.g., dilation and curettage, termination of pregnancy, insertion of an intrauterine device [IUD], or


InternalMed_Harrison

InternalMed_Harrison. and usually sexually transmitted) or secondary to invasive intrauterine surgical procedures (e.g., dilation and curettage, termination of pregnancy, insertion of an intrauterine device [IUD], or hysterosalpingography) or to parturition.


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InternalMed_Harrison. Etiology The agents most often implicated in acute PID include the primary causes of endocervicitis (e.g., N. gonorrhoeae and C. trachomatis) and organisms that can be regarded as components of an altered vaginal microbiota. In general, PID is most often caused by N. gonorrhoeae where there is a high incidence of gonorrhea—e.g., in inner-city populations in the United States. In case–control studies, M. genitalium has also been significantly associated with histopathologic diagnoses of endometritis and with salpingitis.


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InternalMed_Harrison. Anaerobic and facultative organisms (especially Prevotella species, peptostreptococci, E. coli, Haemophilus influenzae, and group B streptococci) as well as genital mycoplasmas have been isolated from the peritoneal fluid or fallopian tubes in a varying proportion (typically one-fourth to one-third) of women with PID studied in the United States. The difficulty of determining the exact microbial etiology of an individual case of PID—short of using invasive procedures for specimen collection—has implications for the approach to empirical antimicrobial treatment of this infection.


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InternalMed_Harrison. Epidemiology In the United States, the estimated annual number of initial visits to physicians’ offices for PID by women 15–44 years of age fell from an average of 400,000 during the 1980s to 250,000 in 1999 and then to 90,000 in 2011. Hospitalizations for acute PID in the United States also declined steadily throughout the 1980s and early 1990s but have remained fairly constant at 70,000–100,000 per year since 1995. Important risk factors for acute PID include the presence of endocervical infection or bacterial vaginosis, a history of salpingitis or of recent vaginal douching, and recent insertion of an IUD. Certain other iatrogenic factors, such as dilation and curettage or cesarean section, can increase the risk of PID, especially among women with endocervical gonococcal or chlamydial infection or bacterial vaginosis. Symptoms of N. gonorrhoeae–associated and C. trachomatis–associated PID often begin during or soon after the menstrual period; this timing suggests that menstruation


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InternalMed_Harrison. infection or bacterial vaginosis. Symptoms of N. gonorrhoeae–associated and C. trachomatis–associated PID often begin during or soon after the menstrual period; this timing suggests that menstruation is a risk factor for ascending infection from the cervix and vagina. Experimental inoculation of the fallopian tubes of nonhuman primates has shown that repeated exposure to


InternalMed_Harrison

InternalMed_Harrison. C. trachomatis leads to the greatest degree of tissue inflammation and damage; thus, immunopathology probably contributes to the pathogenesis of chlamydial salpingitis. Women using oral contraceptives appear to be at decreased risk of symptomatic PID, and tubal sterilization reduces the risk of salpingitis by preventing intraluminal spread of infection into the tubes. Clinical Manifestations • endometritis: a clinical patHologic syndrome


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InternalMed_Harrison. A study of women with clinically suspected PID who were undergoing both endometrial biopsy and laparoscopy showed that those with endometritis alone differed from those who also had salpingitis in significantly less often having lower-quadrant, adnexal, or cervical motion or abdominal rebound tenderness; fever; or elevated C-reactive protein levels. In addition, women with endometritis alone differed from those with neither endometritis nor salpingitis in more often having gonorrhea, chlamydial infection, and risk factors such as douching or IUD use. Thus, women with endometritis alone were intermediate between those with neither endometritis nor salpingitis and those with salpingitis with respect to risk factors, clinical manifestations, cervical infection prevalence, and elevated C-reactive protein level. Women with endometritis alone are at lower risk of subsequent tubal occlusion and resulting infertility than are those with salpingitis.


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InternalMed_Harrison. salpingitis Symptoms of nontuberculous salpingitis classically evolve from a yellow or malodorous vaginal discharge caused by MPC and/ or bacterial vaginosis to midline abdominal pain and abnormal vaginal bleeding caused by endometritis and then to bilateral lower abdominal and pelvic pain caused by salpingitis, with nausea, vomiting, and increased abdominal tenderness if peritonitis develops. The abdominal pain in nontuberculous salpingitis is usually described as dull or aching. In some cases, pain is lacking or atypical, but active inflammatory changes are found in the course of an unrelated evaluation or procedure, such as a laparoscopic evaluation 877 for infertility. Abnormal uterine bleeding precedes or coincides with the onset of pain in ~40% of women with PID, symptoms of urethritis (dysuria) occur in 20%, and symptoms of proctitis (anorectal pain, tenesmus, and rectal discharge or bleeding) are occasionally seen in women with gonococcal or chlamydial infection.


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InternalMed_Harrison. Speculum examination shows evidence of MPC (yellow endocervical discharge, easily induced endocervical bleeding) in the majority of women with gonococcal or chlamydial PID. Cervical motion tenderness is produced by stretching of the adnexal attachments on the side toward which the cervix is pushed. Bimanual examination reveals uterine fundal tenderness due to endometritis and abnormal adnexal tenderness due to salpingitis that is usually, but not necessarily, bilateral. Adnexal swelling is palpable in about one-half of women with acute salpingitis, but evaluation of the adnexae in a patient with marked tenderness is not reliable. The initial temperature is >38°C in only about one-third of patients with acute salpingitis. Laboratory findings include elevation of the erythrocyte sedimentation rate (ESR) in 75% of patients with acute salpingitis and elevation of the peripheral white blood cell count in up to 60%.


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InternalMed_Harrison. Unlike nontuberculous salpingitis, genital tuberculosis often occurs in older women, many of whom are postmenopausal. Presenting symptoms include abnormal vaginal bleeding, pain (including dysmenorrhea), and infertility. About one-quarter of these women have had adnexal masses. Endometrial biopsy shows tuberculous granulomas and provides optimal specimens for culture.


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InternalMed_Harrison. periHepatitis and periappendicitis Pleuritic upper-abdominal pain and tenderness, usually localized to the right upper quadrant (RUQ), develop in 3–10% of women with acute PID. Symptoms of perihepatitis arise during or after the onset of symptoms of PID and may overshadow lower abdominal symptoms, thereby leading to a mistaken diagnosis of cholecystitis. In perhaps 5% of cases of acute salpingitis, early laparoscopy reveals perihepatic inflammation ranging from edema and erythema of the liver capsule to exudate with fibrinous adhesions between the visceral and parietal peritoneum. When treatment is delayed and laparoscopy is performed late, dense “violin-string” adhesions can be seen over the liver; chronic exertional or positional RUQ pain ensues when traction is placed on the adhesions. Although perihepatitis, also known as the Fitz-Hugh–Curtis syndrome, was for many years specifically attributed to gonococcal salpingitis, most cases are now attributed to chlamydial salpingitis. In


InternalMed_Harrison

InternalMed_Harrison. Although perihepatitis, also known as the Fitz-Hugh–Curtis syndrome, was for many years specifically attributed to gonococcal salpingitis, most cases are now attributed to chlamydial salpingitis. In patients with chlamydial salpingitis, serum titers of microimmunofluorescent antibody to C. trachomatis are typically much higher when perihepatitis is present than when it is absent.


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InternalMed_Harrison. Physical findings include RUQ tenderness and usually include adnexal tenderness and cervicitis, even in patients whose symptoms do not suggest salpingitis. Results of liver function tests and RUQ ultrasonography are nearly always normal. The presence of MPC and pelvic tenderness in a young woman with subacute pleuritic RUQ pain and normal ultrasonography of the gallbladder points to a diagnosis of perihepatitis. Periappendicitis (appendiceal serositis without involvement of the intestinal mucosa) has been found in ~5% of patients undergoing appendectomy for suspected appendicitis and can occur as a complication of gonococcal or chlamydial salpingitis.


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InternalMed_Harrison. Among women with salpingitis, HIV infection is associated with increased severity of salpingitis and with tuboovarian abscess requiring hospitalization and surgical drainage. Nonetheless, among women with HIV infection and salpingitis, the clinical response to conventional antimicrobial therapy (coupled with drainage of tuboovarian abscess, when found) has usually been satisfactory. Diagnosis Treatment appropriate for PID must not be withheld from patients who have an equivocal diagnosis; it is better to err on the side of overdiagnosis and overtreatment. On the other hand, it is essential to differentiate between salpingitis and other pelvic pathology, particularly surgical emergencies such as appendicitis and ectopic pregnancy. Nothing short of laparoscopy definitively identifies salpingitis, but routine laparoscopy to confirm suspected salpingitis is generally


InternalMed_Harrison

InternalMed_Harrison. Sexually Transmitted Infections: Overview and Clinical Approach 878 impractical. Most patients with acute PID have lower abdominal pain of <3 weeks’ duration, pelvic tenderness on bimanual pelvic examination, and evidence of lower genital tract infection (e.g., MPC). Approximately 60% of such patients have salpingitis at laparoscopy, and perhaps 10–20% have endometritis alone. Among the patients with these findings, a rectal temperature >38°C, a palpable adnexal mass, and elevation of the ESR to >15 mm/h also raise the probability of salpingitis, which has been found at laparoscopy in 68% of patients with one of these additional findings, 90% of patients with two, and 96% of patients with three. However, only 17% of all patients with laparoscopy-confirmed salpingitis have had all three additional findings. In a woman with pelvic pain and tenderness, increased numbers of PMNs (30 per 1000× microscopic field in strands of cervical mucus) or leukocytes outnumbering epithelial cells in


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InternalMed_Harrison. additional findings. In a woman with pelvic pain and tenderness, increased numbers of PMNs (30 per 1000× microscopic field in strands of cervical mucus) or leukocytes outnumbering epithelial cells in vaginal fluid (in the absence of trichomonal vaginitis, which also produces PMNs in vaginal discharge) increase the predictive value of a clinical diagnosis of acute PID, as do onset with menses, history of recent abnormal menstrual bleeding, presence of an IUD, history of salpingitis, and sexual exposure to a male with urethritis. Appendicitis or another disorder of the gut is favored by the early onset of anorexia, nausea, or vomiting; the onset of pain later than day 14 of the menstrual cycle; or unilateral pain limited to the right or left lower quadrant. Whenever the diagnosis of PID is being considered, serum assays for human β-chorionic gonadotropin should be performed; these tests are usually positive with ectopic pregnancy. Ultrasonography and magnetic resonance imaging (MRI) can


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InternalMed_Harrison. considered, serum assays for human β-chorionic gonadotropin should be performed; these tests are usually positive with ectopic pregnancy. Ultrasonography and magnetic resonance imaging (MRI) can be useful for the identification of tuboovarian or pelvic abscess. MRI of the tubes can also show increased tubal diameter, intratubal fluid, or tubal wall thickening in cases of salpingitis. The primary and uncontested value of laparoscopy in women with lower abdominal pain is for the exclusion of other surgical problems. Some of the most common or serious problems that may be confused with salpingitis (e.g., acute appendicitis, ectopic pregnancy, corpus luteum bleeding, ovarian tumor) are unilateral. Unilateral pain or pelvic mass, although not incompatible with PID, is a strong indication for laparoscopy unless the clinical picture warrants laparotomy instead. Atypical clinical findings such as the absence of lower genital tract infection, a missed menstrual period, a positive pregnancy


InternalMed_Harrison

InternalMed_Harrison. laparoscopy unless the clinical picture warrants laparotomy instead. Atypical clinical findings such as the absence of lower genital tract infection, a missed menstrual period, a positive pregnancy test, or failure to respond to appropriate therapy are other common indications for laparoscopy. Endometrial biopsy is relatively sensitive and specific for the diagnosis of endometritis, which correlates well with the presence of salpingitis. Vaginal or endocervical swab specimens should be examined by NAATs for N. gonorrhoeae and C. trachomatis. At a minimum, vaginal fluid should be evaluated for the presence of PMNs, and endocervical secretions ideally should be assessed by Gram’s staining for PMNs and gram-negative diplococci, which indicate gonococcal infection. The clinical diagnosis of PID made by expert gynecologists is confirmed by laparoscopy or endometrial biopsy in ~90% of women who also have cultures positive for N. gonorrhoeae or


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InternalMed_Harrison. C. trachomatis. Even among women with no symptoms suggestive of acute PID who were attending an STD clinic or a gynecology clinic in Pittsburgh, endometritis was significantly associated with endocervical gonorrhea or chlamydial infection or with bacterial vaginosis, being detected in 26%, 27%, and 15% of women with these conditions, respectively. Recommended combination regimens for ambulatory or parenteral management of PID are presented in Table 163-6. Women managed as outpatients should receive a combined regimen with broad activity, such as ceftriaxone (to cover possible gonococcal infection) followed by doxycycline (to cover possible chlamydial infection). Metronidazole can be added, if tolerated, to enhance activity against anaerobes; this addition should be strongly considered if bacterial vaginosis is documented. Although few methodologically sound clinical trials (especially with prolonged follow-up) have been


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InternalMed_Harrison. Ceftriaxone (250 mg IM once) Initiate parenteral therapy with either of the following regimens; continue to outpatient therapy, as described plusb in the text Gentamicin (loading dose of 2 mg/kg IV or IM, then maintenance dose of 1.5 mg/kg q8h) aSee text for discussion of options in the patient who is intolerant of cephalosporins. bThe addition of metronidazole is recommended by some experts, particularly if bacterial vaginosis is present. Source: Adapted from Centers for Disease Control and Prevention: MMWR Recomm Rep 59(RR-12):1, 2010. conducted, one meta-analysis suggested a benefit of providing good coverage against anaerobes.


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InternalMed_Harrison. The CDC STD treatment guidelines recommend initiation of empirical treatment for PID in sexually active young women and other women at risk for PID if they are experiencing pelvic or lower abdominal pain, if no other cause for the pain can be identified, and if pelvic examination reveals one or more of the following criteria for PID: cervical motion tenderness, uterine tenderness, or adnexal tenderness. Women with suspected PID can be treated as either outpatients or inpatients. In the multicenter Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) trial, 831 women with mild to moderately severe symptoms and signs of PID were randomized to receive either inpatient treatment with IV cefoxitin and doxycycline or outpatient treatment with a single IM dose of cefoxitin plus oral doxycycline. Short-term clinical and microbiologic outcomes and long-term outcomes were equivalent in the two groups. Nonetheless, hospitalization should be considered when (1) the diagnosis is


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InternalMed_Harrison. oral doxycycline. Short-term clinical and microbiologic outcomes and long-term outcomes were equivalent in the two groups. Nonetheless, hospitalization should be considered when (1) the diagnosis is uncertain and surgical emergencies such as appendicitis and ectopic pregnancy cannot be excluded, (2) the patient is pregnant, (3) pelvic abscess is suspected, (4) severe illness or nausea and vomiting preclude outpatient management, (5) the patient has HIV infection, (6) the patient is assessed as unable to follow or tolerate an outpatient regimen, or (7) the patient has failed to respond to outpatient therapy. Some experts also prefer to hospitalize adolescents with PID for initial therapy, although younger women do as well as older women on outpatient therapy.


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InternalMed_Harrison. Currently, oral cephalosporins, doxycycline, and the fluoroquinolones do not provide reliable coverage for gonococcal infection. Thus, adequate oral treatment of women with serious intolerance to cephalosporins is a challenge. If penicillins are an option, amoxicillin/ clavulanic acid combined with doxycycline has elicited a short-term clinical response in one trial. If fluoroquinolones are the only option and if the community prevalence and individual risk of gonorrhea are known to be low, oral levofloxacin (500 mg once daily) or ofloxacin (400 mg twice daily) for 14 days, with or without metronidazole, may be considered; moreover, clinical trials performed outside the United States support the effectiveness of oral moxifloxacin. In this case, it is imperative to perform a sensitive diagnostic test for gonorrhea (ideally, culture to test for antimicrobial susceptibility) before initiation of therapy. For women whose PID involves quinolone-resistant


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InternalMed_Harrison. N. gonorrhoeae, treatment is uncertain but could include parenteral gentamicin or oral azithromycin, although the latter agent has not been studied for this purpose. For hospitalized patients, the following two parenteral regimens (Table 163-6) have given nearly identical results in a multicenter randomized trial: 1. Doxycycline plus either cefotetan or cefoxitin: Administration of these drugs should be continued by the IV route for at least 48 h after the patient’s condition improves and then followed with oral doxycycline (100 mg twice daily) to complete 14 days of therapy. 2.


InternalMed_Harrison

InternalMed_Harrison. 2. Clindamycin plus gentamicin in patients with normal renal function: Once-daily administration of gentamicin (with combination of the total daily dose into a single daily dose) has not been evaluated in PID but has been efficacious in other serious infections and could be substituted. Treatment with these drugs should be continued for at least 48 h after the patient’s condition improves and then followed with oral doxycycline (100 mg twice daily) or clindamycin (450 mg four times daily) to complete 14 days of therapy. In cases with tuboovarian abscess, clindamycin rather than doxycycline for continued therapy provides better coverage for anaerobic infection.


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InternalMed_Harrison. Hospitalized patients should show substantial clinical improvement within 3–5 days. Women treated as outpatients should be clinically reevaluated within 72 h. A follow-up telephone survey of women seen in an emergency department and given a prescription for 10 days of oral doxycycline for PID found that 28% never filled the prescription and 41% stopped taking the medication early (after an average of 4.1 days), often because of persistent symptoms, lack of symptoms, or side effects. Women not responding favorably to ambulatory therapy should be hospitalized for parenteral therapy and further diagnostic evaluations, including a consideration of laparoscopy. Male sex partners should be evaluated and treated empirically for gonorrhea and chlamydial infection. After completion of treatment, tests for persistent or recurrent infection with


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InternalMed_Harrison. N. gonorrhoeae or C. trachomatis should be performed if symptoms persist or recur or if the patient has not complied with therapy or has been reexposed to an untreated sex partner. Surgery is necessary for the treatment of salpingitis only in the face of life-threatening infection (such as rupture or threatened rupture of a tuboovarian abscess) or for drainage of an abscess. Conservative surgical procedures are usually sufficient. Pelvic abscesses can often be drained by posterior colpotomy, and peritoneal lavage can be used for generalized peritonitis.


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InternalMed_Harrison. Prognosis Late sequelae include infertility due to bilateral tubal occlusion, ectopic pregnancy due to tubal scarring without occlusion, chronic pelvic pain, and recurrent salpingitis. The overall post-salpingitis risk of infertility due to tubal occlusion in a large study in Sweden was 11% after one episode of salpingitis, 23% after two episodes, and 54% after three or more episodes. A University of Washington study found a sevenfold increase in the risk of ectopic pregnancy and an eightfold increase in the rate of hysterectomy after PID.


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InternalMed_Harrison. Prevention A randomized controlled trial designed to determine whether selective screening for chlamydial infection reduces the risk of subsequent PID showed that women randomized to undergo screening had a 56% lower rate of PID over the following year than did women receiving the usual care without screening. This report helped prompt U.S. national guidelines for risk-based chlamydial screening of young women to reduce the incidence of PID and the prevalence of post-PID sequelae, while also reducing sexual transmission of C. trachomatis. The CDC and the U.S. Preventive Services Task Force recommend that sexually active women ≤25 years of age be screened for genital chlamydial infection annually. Despite this recommenda-879 tion, screening coverage in many primary care settings remains low.


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InternalMed_Harrison. Genital ulceration reflects a set of important STIs, most of which sharply increase the risk of sexual acquisition and shedding of HIV. In a 1996 study of genital ulcers in 10 of the U.S. cities with the highest rates of primary syphilis, PCR testing of ulcer specimens demonstrated HSV in 62% of patients, Treponema pallidum (the cause of syphilis) in 13%, and Haemophilus ducreyi (the cause of chancroid) in 12–20%. Today, genital herpes represents an even higher proportion of genital ulcers in the United States and other industrialized countries.


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InternalMed_Harrison. In Asia and Africa, chancroid (Fig. 163-5) was once considered the most common type of genital ulcer, followed in frequency by primary syphilis and then genital herpes (Fig. 163-6). With increased efforts to control chancroid and syphilis and widespread use of broad-spectrum antibiotics to treat STI-related syndromes, together with more frequent recurrences or persistence of genital herpes attributable to HIV infection, PCR testing of genital ulcers now clearly implicates genital herpes as by far the most common cause of genital ulceration in most developing countries. LGV due to C. trachomatis (Fig. 163-7) and donovanosis (granuloma inguinale, due to Klebsiella granulomatis; see Fig. 198e-1) continue to cause genital ulceration in some developing countries. LGV virtually disappeared in industrialized countries during the first 20 years of the HIV pandemic, but outbreaks are again occurring in Europe (including the United Kingdom), in North America, and in Australia. In these


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InternalMed_Harrison. in industrialized countries during the first 20 years of the HIV pandemic, but outbreaks are again occurring in Europe (including the United Kingdom), in North America, and in Australia. In these outbreaks, LGV typically presents as proctitis, with or without anal lesions, in men who report unprotected receptive anal intercourse, very often in association with HIV and/or hepatitis C virus infection; the latter may be an acute infection acquired through the same exposure. Other causes of genital ulcers include (1) candidiasis and traumatized genital warts—both readily recognized; (2) lesions due to genital involvement by more widespread dermatoses; (3) cutaneous manifestations of systemic diseases such as genital mucosal ulceration in Stevens-Johnson syndrome or Behçet’s disease; (4) superinfections of lesions that may originally have been sexually acquired (for example, methicillin-resistant S. aureus complicating a genital ulcer due to HSV-2); and (5) localized drug reactions, such


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InternalMed_Harrison. of lesions that may originally have been sexually acquired (for example, methicillin-resistant S. aureus complicating a genital ulcer due to HSV-2); and (5) localized drug reactions, such as the ulcers occasionally seen with topical paromomycin cream or boric acid preparations.


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InternalMed_Harrison. Diagnosis Although most genital ulcerations cannot be diagnosed confidently on clinical grounds alone, clinical findings (Table 163-7) FIGURE 163-5 Chancroid: multiple, painful, punched-out ulcers with undermined borders on the labia occurring after autoinoculation. Sexually Transmitted Infections: Overview and Clinical Approach FIGURE 163-6 Genital herpes. A relatively mild, superficial ulcer is typically seen in episodic outbreaks. (Courtesy of Michael Remington, University of Washington Virology Research Clinic.) FIGURE 163-7 Lymphogranuloma venereum (LGV): striking ten-der lymphadenopathy occurring at the femoral and inguinal lymph nodes, separated by a groove made by Poupart’s ligament. This “sign-of-the-groove” is not considered specific for LGV; for example, lym-phomas may present with this sign. InITIAL MAnAgEMEnT of gEnITAL oR PERIAnAL uLCER


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InternalMed_Harrison. InITIAL MAnAgEMEnT of gEnITAL oR PERIAnAL uLCER Dark-field exam (if available), direct FA, or PCR for T. pallidum RPR, VDRL, or EIA serologic test for syphilisa Culture, direct FA, ELISA, or PCR for HSV HSV-2-specific serology (consider) In chancroid-endemic area: PCR or culture for H. ducreyi Herpes confirmed or suspected (history or sign of vesicles): Treat for genital herpes with acyclovir, valacyclovir, or famciclovir. Syphilis confirmed (dark-field, FA, or PCR showing T. pallidum, or RPR reactive): Benzathine penicillin (2.4 million units IM once to patient, to recent [e.g., within 3 months] seronegative partner[s], and to all seropositive partners)b Chancroid confirmed or suspected (diagnostic test positive, or HSV and syphilis excluded, and persistent lesion): Ciprofloxacin (500 mg PO as single dose) or Ceftriaxone (250 mg IM as single dose) or


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InternalMed_Harrison. Ciprofloxacin (500 mg PO as single dose) or Ceftriaxone (250 mg IM as single dose) or Azithromycin (1 g PO as single dose) aIf results are negative but primary syphilis is suspected, treat presumptively when indicated by epidemiologic and sexual risk assessment; repeat in 1 week. bThe same treatment regimen is also effective in HIV-infected persons with early syphilis. Abbreviations: EIA, enzyme immunoassay; ELISA, enzyme-linked immunosorbent assay; FA, fluorescent antibody; HSV, herpes simplex virus; PCR, polymerase chain reaction; RPR, rapid plasma reagin; VDRL, Venereal Disease Research Laboratory.


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InternalMed_Harrison. and epidemiologic considerations can usually guide initial management (Table 163-8) pending results of specific tests. Clinicians should order a rapid serologic test for syphilis in all cases of genital ulcer. To evaluate lesions except those highly characteristic of infection with HSV (i.e., those with herpetic vesicles), dark-field microscopy, direct immunofluorescence, and PCR for T. pallidum can be useful but are rarely available today in most countries. It is important to note that 30% of syphilitic chancres—the primary ulcer of syphilis—are associated with an initially nonreactive syphilis serology. All patients presenting with genital ulceration should be counseled and tested for HIV infection. Typical vesicles or pustules or a cluster of painful ulcers preceded by vesiculopustular lesions suggests genital herpes. These typical clinical manifestations make detection of the virus optional; however, many patients want confirmation of the diagnosis, and differentiation of


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InternalMed_Harrison. Source: From RM Ballard, in KK Holmes et al (eds): Sexually Transmitted Diseases, 4th ed. New York, McGraw-Hill, 2008. HSV-1 from HSV-2 has prognostic implications, because the latter causes more frequent genital recurrences. Painless, nontender, indurated ulcers with firm, nontender inguinal adenopathy suggest primary syphilis. If results of dark-field examination and a rapid serologic test for syphilis are initially negative, presumptive therapy should be provided on the basis of the individual’s risk. For example, with increasing rates of syphilis among MSM in the United States, most experts would not withhold therapy for this infection pending watchful waiting and/or subsequent detection of seroconversion. Repeated serologic testing for syphilis 1 or 2 weeks after treatment of seronegative primary syphilis usually demonstrates seroconversion.


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InternalMed_Harrison. “Atypical” or clinically trivial ulcers may be more common manifestations of genital herpes than classic vesiculopustular lesions. Specific tests for HSV in such lesions are therefore indicated (Chap. 216). Commercially available type-specific serologic tests for serum antibody to HSV-2 may give negative results, especially when patients present early with the initial episode of genital herpes or when HSV-1 is the cause of genital herpes (as is often the case today). Furthermore, a positive test for antibody to HSV-2 does not prove that the current lesions are herpetic, because nearly one-fifth of the general population of the United States (and no doubt a higher proportion of those at risk for other STIs) becomes seropositive for HSV-2 during early adulthood. Although even “type-specific” tests for HSV-2 that are commercially available in the United States are not 100% specific, a positive HSV-2 serology does enable the clinician to tell the patient that he or she has probably had


InternalMed_Harrison

InternalMed_Harrison. tests for HSV-2 that are commercially available in the United States are not 100% specific, a positive HSV-2 serology does enable the clinician to tell the patient that he or she has probably had genital herpes, should learn to recognize symptoms, and should avoid sex during recurrences. In addition, because genital shedding and sexual transmission of HSV-2 often occur in the absence of symptoms and signs of recurrent herpetic lesions, persons who have a history of genital herpes or who are seropositive for HSV-2 should consider the use of condoms or suppressive antiviral therapy, both of which can reduce the risk of HSV-2 transmission to a sexual partner.


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InternalMed_Harrison. Demonstration of H. ducreyi by culture (or by PCR, where available) is most useful when ulcers are painful and purulent, especially if inguinal lymphadenopathy with fluctuance or overlying erythema is noted; if chancroid is prevalent in the community; or if the patient has recently had a sexual exposure elsewhere in a chancroid-endemic area (e.g., a developing country). Enlarged, fluctuant lymph nodes should be aspirated for culture or PCR to detect H. ducreyi as well as for Gram’s staining and culture to rule out the presence of other pyogenic bacteria.


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InternalMed_Harrison. When genital ulcers persist beyond the natural history of initial episodes of herpes (2–3 weeks) or of chancroid or syphilis (up to 6 weeks) and do not resolve with syndrome-based antimicrobial therapy, then— in addition to the usual tests for herpes, syphilis, and chancroid—biopsy is indicated to exclude donovanosis, carcinoma, and other nonvenereal dermatoses. If not performed previously, HIV serology should be standard because chronic, persistent genital herpes is common in AIDS.


InternalMed_Harrison

InternalMed_Harrison. Immediate syndrome-based treatment for acute genital ulcerations (after collection of all necessary diagnostic specimens at the first visit) is often appropriate before all test results become available because patients with typical initial or recurrent episodes of genital or anorectal herpes can benefit from prompt oral antiviral therapy (Chap. 216); because early treatment of sexually transmitted causes of genital ulcers decreases further transmission; and because many patients do not return for test results and treatment. A thorough assessment of the patient’s sexual-risk profile and medical history is critical in determining the course of initial management. The patient who has risk factors consistent with exposure to syphilis (e.g., a male patient who reports sex with other men or who has HIV infection) should generally receive initial treatment for syphilis. Empirical therapy for chancroid should be considered if there has been an exposure in an area of the world where chancroid


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InternalMed_Harrison. has HIV infection) should generally receive initial treatment for syphilis. Empirical therapy for chancroid should be considered if there has been an exposure in an area of the world where chancroid occurs or if regional lymph node suppuration is evident. In resource-poor settings lacking ready access to diagnostic tests, this approach to 881 syndromic treatment for syphilis and chancroid has helped bring these two diseases under control. Finally, empirical antimicrobial therapy may be indicated if ulcers persist and the diagnosis remains unclear after a week of observation despite attempts to diagnose herpes, syphilis, and chancroid.


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InternalMed_Harrison. PROCTITIS, PROCTOCOLITIS, ENTEROCOLITIS, AND ENTERITIS


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InternalMed_Harrison. Sexually acquired proctitis, with inflammation limited to the rectal mucosa (the distal 10–12 cm), results from direct rectal inoculation of typical STD pathogens. In contrast, inflammation extending from the rectum to the colon (proctocolitis), involving both the small and the large bowel (enterocolitis), or involving the small bowel alone (enteritis) can result from ingestion of typical intestinal pathogens through oral–anal exposure during sexual contact. Anorectal pain and mucopurulent, bloody rectal discharge suggest proctitis or protocolitis. Proctitis commonly produces tenesmus (causing frequent attempts to defecate, but not true diarrhea) and constipation, whereas proctocolitis and enterocolitis more often cause true diarrhea. In all three conditions, anoscopy usually shows mucosal exudate and easily induced mucosal bleeding (i.e., a positive “wipe test”), sometimes with petechiae or mucosal ulcers. Exudate should be sampled for Gram’s staining and other microbiologic studies.


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InternalMed_Harrison. exudate and easily induced mucosal bleeding (i.e., a positive “wipe test”), sometimes with petechiae or mucosal ulcers. Exudate should be sampled for Gram’s staining and other microbiologic studies. Sigmoidoscopy or colonoscopy shows inflammation limited to the rectum in proctitis or disease extending at least up into the sigmoid colon in proctocolitis.


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InternalMed_Harrison. The AIDS era brought an extraordinary shift in the clinical and etiologic spectrum of intestinal infections among MSM. The number of cases of the acute intestinal STIs described above fell as high-risk sexual behaviors became less common in this group. At the same time, the number of AIDS-related opportunistic intestinal infections increased rapidly, many associated with chronic or recurrent symptoms. The incidence of these opportunistic infections has since fallen with increasingly widespread coverage of HIV-infected persons with effective antiretroviral therapy. Two species initially isolated in association with intestinal symptoms in MSM—now known as Helicobacter cinaedi and H. fennelliae—have both been isolated from the blood of HIV-infected men and other immunosuppressed persons, often in association with a syndrome of multifocal dermatitis and arthritis.


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InternalMed_Harrison. H. fennelliae—have both been isolated from the blood of HIV-infected men and other immunosuppressed persons, often in association with a syndrome of multifocal dermatitis and arthritis. Acquisition of HSV, N. gonorrhoeae, or C. trachomatis (including LGV strains of C. trachomatis) during receptive anorectal intercourse causes most cases of infectious proctitis in women and MSM. Primary and secondary syphilis can also produce anal or anorectal lesions, with or without symptoms. Gonococcal or chlamydial proctitis typically involves the most distal rectal mucosa and the anal crypts and is clinically mild, without systemic manifestations. In contrast, primary proctitis due to HSV and proctocolitis due to the strains of


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InternalMed_Harrison. C. trachomatis that cause LGV usually produce severe anorectal pain and often cause fever. Perianal ulcers and inguinal lymphadenopathy, most commonly due to HSV, can also occur with LGV or syphilis. Sacral nerve root radiculopathies, usually presenting as urinary retention, laxity of the anal sphincter, or constipation, may complicate primary herpetic proctitis. In LGV, rectal biopsy typically shows crypt abscesses, granulomas, and giant cells—findings resembling those in Crohn’s disease; such findings should always prompt rectal culture and serology for LGV, which is a curable infection. Syphilis can also produce rectal granulomas, usually in association with infiltration by plasma cells or other mononuclear cells. Syphilis, LGV, and HSV infection involving the rectum can produce perirectal adenopathy that is sometimes mistaken for malignancy; syphilis, LGV, HSV infection, and chancroid involving the anus can produce inguinal adenopathy because anal lymphatics drain to inguinal


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InternalMed_Harrison. adenopathy that is sometimes mistaken for malignancy; syphilis, LGV, HSV infection, and chancroid involving the anus can produce inguinal adenopathy because anal lymphatics drain to inguinal lymph nodes.


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InternalMed_Harrison. Diarrhea and abdominal bloating or cramping pain without anorectal symptoms and with normal findings on anoscopy and sigmoidoscopy occur with inflammation of the small intestine (enteritis) or with proximal colitis. In MSM without HIV infection, enteritis is often attributable to Giardia lamblia. Sexually acquired proctocolitis is most often due to Campylobacter or Shigella species. Sexually Transmitted Infections: Overview and Clinical Approach TREATMEnT ProcTITIs, ProcTocolITIs, enTerocolITIs, And enTerITIs


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InternalMed_Harrison. Acute proctitis in persons who have practiced receptive anorectal intercourse is usually sexually acquired. Such patients should undergo anoscopy to detect rectal ulcers or vesicles and petechiae after swabbing of the rectal mucosa; to examine rectal exudates for PMNs and gram-negative diplococci; and to obtain rectal swab specimens for testing for rectal gonorrhea, chlamydial infection, herpes, and syphilis. Pending test results, patients with proctitis should receive empirical syndromic treatment—e.g., with ceftriaxone (a single IM dose of 250 mg for gonorrhea) plus doxycycline (100 mg by mouth twice daily for 7 days) for possible chlamydial infection plus treatment for herpes or syphilis if indicated. If LGV proctitis is proven or suspected, the recommended treatment is doxycycline (100 mg by mouth twice daily for 21 days); alternatively, 1 g of azithromycin once a week for 3 weeks is likely to be effective but is little studied.


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InternalMed_Harrison. Prevention and control of STIs require the following: 1. Reduction of the average rate of sexual exposure to STIs through alteration of sexual risk behaviors and behavioral norms among both susceptible and infected persons in all population groups. The necessary changes include reduction in the total number of sexual partners and the number of concurrent sexual partners. 2.


InternalMed_Harrison

InternalMed_Harrison. 2. Reduction of the efficiency of transmission through the promotion of safer sexual practices, the use of condoms during casual or commercial sex, vaccination against HBV and HPV infection, male circumcision (which reduces risk of acquisition of HIV infection, chancroid, and perhaps other STIs), and a growing number of other approaches (e.g., early detection and treatment of other STIs to reduce the efficiency of sexual transmission of HIV). Longitudinal studies have shown that consistent condom use is associated with significant protection of both males and females against all STIs that have been examined, including HIV, HPV, and HSV infections as well as gonorrhea and chlamydial infection. The only exceptions are probably sexually transmitted Pthirus pubis and Sarcoptes scabiei infestations. 3. Shortening of the duration of infectivity of STIs through early detection and curative or suppressive treatment of patients and their sexual partners.


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InternalMed_Harrison. 3. Shortening of the duration of infectivity of STIs through early detection and curative or suppressive treatment of patients and their sexual partners. Financial and time constraints imposed by many clinical practices, along with the reluctance of some clinicians to ask questions about stigmatized sexual behaviors, often curtail screening and prevention services. As outlined in Fig. 163-8, the success of clinicians’ efforts to detect and treat STIs depends in part on societal efforts to teach young people how to recognize symptoms of STIs; to motivate individuals with symptoms to seek care promptly; to educate persons who are at risk but have no symptoms about what tests they should undergo routinely; and to make high-quality, appropriate care accessible, affordable, and acceptable, especially to the young indigent patients most likely to acquire an STI.


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InternalMed_Harrison. Because many infected individuals develop no symptoms or fail to recognize and report symptoms, clinicians should routinely perform an STI risk assessment for teenagers and young adults as a guide to selective screening. As stated earlier, U.S. Preventive Services Task Force Guidelines recommend screening sexually active female patients ≤25 years of age for C. trachomatis whenever they present for health care (at least once a year); older women should be tested if they have more than one sexual partner, have begun a new sexual relationship since the previous test, or have another STI diagnosed. In women 25–29 years of age, chlamydial infection is uncommon but still may reach a prevalence of 3–5% in some settings; information provided by women in this age group on a sex partner’s concurrency (whether a male partner has had another sex partner during the time they have been together) is helpful in identifying women at increased risk. In some regions of the United States, widespread


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InternalMed_Harrison. (whether a male partner has had another sex partner during the time they have been together) is helpful in identifying women at increased risk. In some regions of the United States, widespread selective screening and treatment of young women for cervical C. trachomatis infection have been associated with a 50–60% drop in prevalence. Such screening and treatment also protect the individual woman from PID. Sensitive urine-based genetic amplification tests permit expansion of screening to men, teenage boys, and girls in settings where examination is not planned or is impractical (e.g., during preparticipation sports examinations or during initial medical evaluation of adolescent girls). Vaginal swabs—collected either by the health care provider at a pelvic examination or by the woman herself—are highly sensitive and specific for the diagnosis of chlamydial and gonococcal infection; they are now the preferred type of specimen for screening and diagnosis of these infections.


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InternalMed_Harrison. Number whose behaviors and ecologic settings result in exposure to STDs Number who acquire STDs Number who develop symptoms of STDs Number who perceive the symptoms of STDs Number who promptly seek medical care when symptomatic Number seeking care who have ready access to care Number perceived by clinicians as possibly having STDs Number perceived as possibly having STDs who can be tested for STDs Number with objective evidence of STDs who get proper treatment for STDs Number who comply with treatment Number whose partners are treated and who are not reinfected FIGURE 163-8 Critical control points for preventive and clini-cal interventions against sexually transmitted diseases (STDs). (Adapted from HT Waller and MA Piot: Bull World Health Organ 41:75, 1969 and 43:1, 1970; and from “Resource allocation model for public health planning—a case study of tuberculosis control,” Bull World Health Organ 48 [Suppl], 1973.)


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InternalMed_Harrison. Although gonorrhea is now substantially less common than chlamydial infection in industrialized countries, screening tests for N. gonorrhoeae are still appropriate for women and teenage girls attending STD clinics and for sexually active teens and young women from areas of high gonorrhea prevalence. Multiplex NAATs that combine screening for N. gonorrhoeae and C. trachomatis—and, more recently, for T. vaginalis—in a single low-cost assay now facilitate the prevention and control of these infections for populations at high risk.


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InternalMed_Harrison. All patients who have newly detected STIs or are at high risk for STIs according to routine risk assessment as well as all pregnant women should be encouraged to undergo serologic testing for syphilis and HIV infection, with appropriate HIV counseling before and after testing. Randomized trials have shown that risk-reduction counseling of patients with STIs significantly lowers subsequent risk of acquiring an STI; such counseling should now be considered a standard component of STI management. Preimmunization serologic testing for antibody to HBV is indicated for unvaccinated persons who are known to be at high risk, such as MSM and people who use injection drugs. In most young persons, however, it is more cost-effective to vaccinate against HBV without serologic screening. It is important to recognize that, while immunization against HBV has contributed to marked reductions in the incidence of infection with this virus, the majority of new cases that do occur are acquired through


InternalMed_Harrison

InternalMed_Harrison. to recognize that, while immunization against HBV has contributed to marked reductions in the incidence of infection with this virus, the majority of new cases that do occur are acquired through sex. In 2006, the Advisory Committee on Immunization Practices (ACIP) of the CDC recommended the following: (1) Universal hepatitis B vaccination should be implemented for all unvaccinated adults in settings in which a high proportion of adults have risk factors for HBV infection (e.g., STD clinics, HIV testing and treatment facilities, drug-abuse treatment and prevention settings, health care settings targeting services to injection drug users or MSM, and correctional facilities). (2) In other primary care and specialty medical settings in which adults at risk for HBV infection receive care, health care providers should inform all patients about the health benefits of vaccination, the risk factors for HBV infection, and the persons for whom vaccination is recommended and should vaccinate


InternalMed_Harrison

InternalMed_Harrison. health care providers should inform all patients about the health benefits of vaccination, the risk factors for HBV infection, and the persons for whom vaccination is recommended and should vaccinate adults who report risk factors for HBV infection as well as any adult who requests protection from HBV infection. To promote vaccination in all settings, health care providers should implement standing orders to identify adults recommended for hepatitis B vaccination, should administer hepatitis B vaccine as part of routine clinical services, should not require acknowledgment of an HBV infection risk factor for adult vaccination, and should use available reimbursement mechanisms to remove financial barriers to hepatitis B vaccination.


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InternalMed_Harrison. In 2007, the ACIP recommended routine immunization of 9to 26-year-old girls and women with the quadrivalent HPV vaccine (against HPV types 6, 11, 16, and 18) approved by the U.S. Food and Drug Administration; the optimal age for recommended vaccination is 11–12 years because of the very high risk of HPV infection after sexual debut. In 2009, the ACIP added bivalent HPV vaccine (against types 6 and 11) as an option and expanded the groups in which immunization (with either quadrivalent or bivalent vaccine) is safe and effective to include boys and men 9–26 years old. HPV vaccines offering broader protection against additional oncogenic HPV types are anticipated. Since 2011, the ACIP has recommended routine administration of quadrivalent HPV vaccine to boys at 11 or 12 years of age and to males 13–21 years of age who have not yet been vaccinated or who have not completed the three-dose vaccine series; men 22–26 years of age may also be vaccinated.


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InternalMed_Harrison. Partner notification is the process of identifying and informing partners of infected patients about possible exposure to an STI and of examining, testing, and treating partners as appropriate. In a series of 22 reports concerning partner notification during the 1990s, index patients with gonorrhea or chlamydial infection named a mean of 0.75–1.6 partners, of whom one-fourth to one-third were infected; those with syphilis named 1.8–6.3 partners, with one-third to one-half infected; and those with HIV infection named 0.76–5.31 partners, with up to one-fourth infected. Persons who transmit infection or who have recently been infected and are still in the incubation period usually have no symptoms or only mild symptoms and seek medical attention only when notified of their exposure. Therefore, the clinician must encourage patients to participate in partner notification, must ensure that exposed persons are notified and treated, and must guarantee confidentiality to all involved. In the


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InternalMed_Harrison. the clinician must encourage patients to participate in partner notification, must ensure that exposed persons are notified and treated, and must guarantee confidentiality to all involved. In the United States, local health departments often offer assistance in partner notification, treatment, and/or counseling. It seems both feasible and most useful to notify those partners exposed within the patient’s likely period of infectiousness, which is often considered the preceding 1 month for gonorrhea, 1–2 months for chlamydial infection, and up to 3 months for early syphilis.


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InternalMed_Harrison. Persons with a new-onset STI always have a source contact who gave them the infection; in addition, they may have a secondary (spread or exposed) contact with whom they had sex after becoming infected. The identification and treatment of these two types of contacts have different objectives. Treatment of the source contact (often a casual contact) benefits the community by preventing further transmission and benefits the source contact; treatment of the recently exposed secondary contact (typically a spouse or another steady sexual partner) prevents the development of serious complications (such as PID) in the partner, reinfection of the index patient, and further spread of infection. A survey of a random sample of U.S. physicians found that most instructed patients to abstain from sex during treatment, to use condoms, and to inform their sex partners after being diagnosed with gonorrhea, chlamydial infection, or syphilis; physicians sometimes gave the patients drugs for their


InternalMed_Harrison

InternalMed_Harrison. sex during treatment, to use condoms, and to inform their sex partners after being diagnosed with gonorrhea, chlamydial infection, or syphilis; physicians sometimes gave the patients drugs for their partners. However, follow-up of the partners by physicians was infrequent. A randomized trial compared patients’ delivery of therapy to partners exposed to gonorrhea or chlamydial infection with conventional notification and advice to partners to seek evaluation for 883 STD; patients’ delivery of partners’ therapy, also known as expedited partner therapy (EPT), significantly reduced combined rates of reinfection of the index patient with N. gonorrhoeae or C. trachomatis. State-by-state variations in regulations governing this approach have not been well defined, but the 2010 CDC STD treatment guidelines and the EPT final report of 2006 (http://www.cdc.gov/std/treatment/ EPTFinalReport2006.pdf) describe its potential use. Currently, EPT is commonly used by many practicing physicians. Its


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InternalMed_Harrison. guidelines and the EPT final report of 2006 (http://www.cdc.gov/std/treatment/ EPTFinalReport2006.pdf) describe its potential use. Currently, EPT is commonly used by many practicing physicians. Its legal status varies by state, but EPT is now permissible in 38 states and potentially allowable in another 9. (Updated information on the legal status of EPT is available at http://www.cdc.gov/std/ept.)


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InternalMed_Harrison. In summary, clinicians and public health agencies share responsibility for the prevention and control of STIs. In the current health care environment, the role of primary care clinicians has become increasingly important in STI prevention as well as in diagnosis and treatment, and the resurgence of bacterial STIs like syphilis and LGV among MSM—particularly those co-infected with HIV—emphasizes Meningitis, Encephalitis, Brain 164 Abscess, and Empyema Karen L. Roos, Kenneth L. Tyler


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InternalMed_Harrison. Meningitis, Encephalitis, Brain 164 Abscess, and Empyema Karen L. Roos, Kenneth L. Tyler Acute infections of the nervous system are among the most important problems in medicine because early recognition, efficient decision making, and rapid institution of therapy can be lifesaving. These distinct clinical syndromes include acute bacterial meningitis, viral meningitis, encephalitis, focal infections such as brain abscess and subdural empyema, and infectious thrombophlebitis. Each may present with a nonspecific prodrome of fever and headache, which in a previously healthy individual may initially be thought to be benign, until (with the exception of viral meningitis) altered consciousness, focal neurologic signs, or seizures appear. Key goals of early management are to emergently distinguish between these conditions, identify the responsible pathogen, and initiate appropriate antimicrobial therapy. APPROACH TO THE PATIENT:


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InternalMed_Harrison. APPROACH TO THE PATIENT: Meningitis, Encephalitis, Brain Abscess, and Empyema (Figure 164-1) The first task is to identify whether an infection predominantly involves the subarachnoid space (meningitis) or whether there is evidence of either generalized or focal involvement of brain tissue in the cerebral hemispheres, cerebellum, or brainstem. When brain tissue is directly injured by a bacterial or viral infection, the disease is referred to as encephalitis, whereas focal infections involving brain tissue are classified as either cerebritis or abscess, depending on the presence or absence of a capsule.


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InternalMed_Harrison. Nuchal rigidity (“stiff neck”) is the pathognomonic sign of meningeal irritation and is present when the neck resists passive flexion. Kernig’s and Brudzinski’s signs are also classic signs of meningeal irritation. Kernig’s sign is elicited with the patient in the supine position. The thigh is flexed on the abdomen, with the knee flexed; attempts to passively extend the knee elicit pain when meningeal irritation is present. Brudzinski’s sign is elicited with the patient in the supine position and is positive when passive flexion of the neck results in spontaneous flexion of the hips and knees. Although commonly tested on physical examinations, the sensitivity and specificity of Kernig’s and Brudzinski’s signs are uncertain. Both may be absent or reduced in very young or elderly patients, immunocompromised individuals, or patients with a severely depressed


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InternalMed_Harrison. Meningitis, Encephalitis, Brain Abscess, and Empyema mental status. The high prevalence of cervical spine disease in older individuals may result in false-positive tests for nuchal rigidity.


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InternalMed_Harrison. Initial management can be guided by several considerations: (1) Empirical therapy should be initiated promptly whenever bacterial meningitis is a significant diagnostic consideration. (2) All patients who have had recent head trauma, are immunocompromised, have known malignant lesions or central nervous system (CNS) neoplasms, or have focal neurologic findings, papilledema, or a depressed level of consciousness should undergo computed tomography (CT) or magnetic resonance imaging (MRI) of the brain prior to lumbar puncture (LP). In these cases empirical antibiotic therapy should not be delayed pending test results but should be administered prior to neuroimaging and LP. (3) A significantly depressed level of consciousness (e.g., somnolence, coma), seizures, or focal neurologic deficits do not occur in viral meningitis; patients with these symptoms should be hospitalized for further evaluation and treated empirically for bacterial and viral meningoencephalitis. (4) Immunocompetent


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InternalMed_Harrison. do not occur in viral meningitis; patients with these symptoms should be hospitalized for further evaluation and treated empirically for bacterial and viral meningoencephalitis. (4) Immunocompetent patients with a normal level of consciousness, no prior antimicrobial treatment, and a cerebrospinal fluid (CSF) profile consistent with viral meningitis (lymphocytic pleocytosis and a normal glucose concentration) can often be treated as outpatients if appropriate contact and monitoring can be ensured. Failure of a patient with suspected viral meningitis to improve within 48 h should prompt a reevaluation including follow-up neurologic and general medical examination and repeat imaging and laboratory studies, often including a second LP.


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InternalMed_Harrison. ADEM Encephalitis Bacterial process Appropriate medical and/or surgical interventions Pleocytosis with PMNs Elevated protein Decreased glucose Gram’s stain positive Tier 1 Eval (no unusual historic points or exposures): Viral: CSF PCR for enterovirus, HSV, VZVPleocytosis with MNCs Normal or increased protein Normal or decreased glucose Gram’s stain negative Abscess or tumor White matter abnormalities Focal or generalized gray matter abnormalities or normal No mass lesion Yes Yes No No Headache, Fever, ±Nuchal Rigidity Altered mental status? Immediate blood culture and lumbar puncture Meningoencephalitis, ADEM, encephalopathy, or mass lesion Imaging: Head CT or MRI (preferred) Mass lesion Obtain blood culture and start empirical antimicrobial therapy Meningitis Papilledema and/or focal neurologic deficit? Immunocompromised? History of recent head trauma, known cancer, sinusitis?