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lnfectious Disease Cryptococcal lnfection Diagnosis and Testing Cryptococcal meningitis is the most common form of meningitis in patients with AIDS, who typically present with headache' Most patients have a CD4 cell count of less than 100/pL. The diagnosis is based on detection of cryptococcal antigen in the CSF or culture of Crgptococcus neoformans in the CSF Serum cryptococcal antigen is positive in 95'l' of patients' The opening CSF pressure is tlpically elevated. Treatment Choose amphotericin B plus fluc1'tosine for induction treatment of meningitis fbllowed by fluconazole maintenance therapy' Maintenance therapy is indicated for patients with AIDS and cryptococcal meningitis until the CD4 cell count is >100/pL for >3 months and the viral load is suppressed. Management of elevated intracranial pressure is by serial therapeutic LPs or extraventricular drain placement.

Treatment Choose amphotericin B plus fluc1'tosine for induction treatment of meningitis fbllowed by fluconazole maintenance therapy' Maintenance therapy is indicated for patients with AIDS and cryptococcal meningitis until the CD4 cell count is >100/pL for >3 months and the viral load is suppressed. Management of elevated intracranial pressure is by serial therapeutic LPs or extraventricular drain placement. Endemic Mycoses STUDY TABLE: Differentiation of Endemic Mycoses lnfection Geographic Distribution What to Look for Blastomycosis Midwestern, southeastern, and south Symptom onset 4-6 weeks after exposure (B I a sto m y ce s d e r m atiti d i s) central United States (Mississippi, Consider in patients with primary skin lesion or concurrent Missouri, and Ohio rivervalleys) pulmonary and skin or bone findings Consider in patients being evaluated forTB, malignanry Coccidiomycosis Southern Arizona, south central Symptom onset 1-3 weeks after exposure (Co cci d i oi d e s species) California, southwestern New Mexico, west Texas Consider in patients with pulmonary symptoms and erythema nodosum or erythema multiforme Consider in patients with pulmonary symptoms and prolonged constitutional symptoms (feve1 fatigue) or meningitis Histoplasmosis Midwestern states in the Ohio and Symptom onset 2-3 weeks after exposure (Histoplasma ca psulatu m) Mississippi river valley regions Consider in patients with complex pulmonary disease (nodular, cavitary, lymphadenopathy)

Endemic Mycoses STUDY TABLE: Differentiation of Endemic Mycoses lnfection Geographic Distribution What to Look for Blastomycosis Midwestern, southeastern, and south Symptom onset 4-6 weeks after exposure (B I a sto m y ce s d e r m atiti d i s) central United States (Mississippi, Consider in patients with primary skin lesion or concurrent Missouri, and Ohio rivervalleys) pulmonary and skin or bone findings Consider in patients being evaluated forTB, malignanry Coccidiomycosis Southern Arizona, south central Symptom onset 1-3 weeks after exposure (Co cci d i oi d e s species) California, southwestern New Mexico, west Texas Consider in patients with pulmonary symptoms and erythema nodosum or erythema multiforme Consider in patients with pulmonary symptoms and prolonged constitutional symptoms (feve1 fatigue) or meningitis Histoplasmosis Midwestern states in the Ohio and Symptom onset 2-3 weeks after exposure (Histoplasma ca psulatu m) Mississippi river valley regions Consider in patients with complex pulmonary disease (nodular, cavitary, lymphadenopathy) Consider in patients being evaluated for sarcoidosis, TB, or malignancy Sporotrichosis Occurs almost exclusively in persons A papule appears days to weeks later at the inoculation site. (Sporoth rix sche nckiil who engage in landscaping or Similar lesions then occur along lymphatic channels proximal gardening to the inoculation site.

Consider in patients being evaluated for sarcoidosis, TB, or malignancy Sporotrichosis Occurs almost exclusively in persons A papule appears days to weeks later at the inoculation site. (Sporoth rix sche nckiil who engage in landscaping or Similar lesions then occur along lymphatic channels proximal gardening to the inoculation site. Sporotrichosis: Ihe most common presentation of sporotrichosis is lymphocutane. ous sporotrichosis. The primary lesion is located at the site of i nocu lation and consists of an ulcerated nodule. Similar lesions occur proximally along the lymphatia. 238

lnfectious Disease Ch I a myd i a tra ch o m ati s I nfecti o n Diagnosis and Testing C. trachomatis may cause cervicitis, urethritis, epididymitis, and proctitis but also may be asymptomatic and lead to ectopic pregnancy, tubal infertility, and chronic pelvic pain syndromes. NAAT is the preferred diagnostic test and can be performed on first-voided urine samples, urethral swabs from men, and vaginal or endocervical swabs from women. Treatment Treat chlamydial infection with azithromycin or doxycycline. I t Neisse ria gonorrhoeae lnfection L t L Diagnosis N. gonorrhoeae infection should be suspected in men with purulent or mucopurulent urethral discharge and in women with L mucopurulent cervicitis. Gonorrhea and Chlamydia trachomatis infection are also common causes of epididymitis in sexually I L active men aged <35 years, proctitis in persons who engage in anal receptive intercourse, and pharyngitis in persons who engage I in oral sex. Infection may be asymptomatic. I l. Disseminated gonococcal infection may cause two syndromes: an arthritis-dermatitis syndrome or purulent arthritis without I L i skin findings. Characteristics of the dermatitis arthritis syndrome include: t i o sparse peripheral necrotic pustules L o monoarthritis or oligoarthritis (knees, hips, and wrists) I o tendon sheath inflammation I Test for terminal component complement deficiency (CHro) as a possible cause of recurrent disseminated gonococcal infection. I I I L t i Testing NAAT is the preferred diagnostic test and can be performed on first-voided urine in men and women; endocervical, urethral, I I I rectal, and pharyngeal swabs may also be used. I I DOil'T BE TRICKED ! . Do not select Gram stain to diagnose gonorrheal cervicitis. . Test for chlamydia, syphilis, and HIV infection in patients I with gonorrhea. 1

t i Testing NAAT is the preferred diagnostic test and can be performed on first-voided urine in men and women; endocervical, urethral, I I I rectal, and pharyngeal swabs may also be used. I I DOil'T BE TRICKED ! . Do not select Gram stain to diagnose gonorrheal cervicitis. . Test for chlamydia, syphilis, and HIV infection in patients I with gonorrhea. 1 Treatment If concurrent chlamydial infection has not been excluded with molecular testing, treat all forms of gonococcal infection with parenteral ceftriaxone and oral doxycycline (preferred) or oral azithromycin (if pregnant). In sexually active men <35 years of age, treat epididymitis with ceftriaxone and azithromycin or Gononhea: Several necrotic pustules and sunounding erythema on the leg associated doxycycline. with disseminated gononhea infection. 239

lnfectious Disease l : DON'T BE TRICKED . Do not select fluoroquinolones to treat gonorrhea because ofantibiotic resistance' l l l : Pelvic I nflammatory Disease : I Diagnosis and Testing PID is a polymicrobial infection of the enclometrium, fallopian tubes, and ovaries that is diagnosed by the presence of uterine a' or adnexal tenderness or cervical motion tenderness accompanied by t'ever and mucopurulent cervical discharge' Select NAAT to diagnose gonorrhea and chlamydia, the primary identifiable causes of PID. All sexually active women should have a pregnancy test to rule out ectopic pregnancy. Treatment Acceptable outpatient treatment regimens include a single parenteral dose of ceftriaxone plus doxycycline with or without metronidazole for 14 days. Choose hospitalization for the following scenarios: . no clinical improvement after 48 to 72 hours of antibiotic treatment . inability to tolerate oral antibiotics . severe illness with nausea, vomiting, or high f'ever e suspected pelvic abscess . pregnancy Inpatients are treated with parenteral cefoxitin or cefotetan and doxycycline. If no improvement is seen in 481o72 hours, choose ultrasonography for evaluation of possible tubo-ovarian abscess. DOil'? BE TRICKED . Screen for other STIs, such as syphilis and HIV Herpes Simplex Virus lnfection Diagnosis and Testing Lesions appear on mucosal surfaces or skin sites as multiple vesicular lesions on an inflamed, erythematous base. Primary infection may also be associated with regional lymphadenopathy, fever, and malaise. Reactivation of latent infection may occur after the primary infection resolves.

Herpes Simplex Virus lnfection Diagnosis and Testing Lesions appear on mucosal surfaces or skin sites as multiple vesicular lesions on an inflamed, erythematous base. Primary infection may also be associated with regional lymphadenopathy, fever, and malaise. Reactivation of latent infection may occur after the primary infection resolves. STUDY IABLE: Selected Herpes Simplex Virus Syndromes Manifestation Description Oral Primary infections are most commonly gingivostomatitis and pharyngitis, whereas herpes labialis is the most frequent sign of reactivation disease Genital herpes Multiple painful vesicular or ulcerative lesions on penis or vulva Recurrent genital herpes is usually caused by HSV-2 (Continued on the nert page) 240

lnfectious Disease STUpY TAEtET Selected Herpes Simplex Virus Syndromes (Continued) Manifestation Description Keratitis Punctate or branching epithelial keratitis Encephalitis Rapid onset of fever, headache, seizures, focal neurologic signs, and impaired consciousness (see Herpes Simplex Encephalitis) Associated with HIV infection Often presents as extensive oral or perianal ulcers (not vesicles) or as esophagitis, colitis, chorioretinitis, acute retinal necrosis, tracheobronchitis, and pneumonia Select PCR testing of specimens obtained from ulcers and mucocutaneous sites. DON'T BE TRICKED . A positive HSV-2 antibody test indicates only previous infection and is not a useful diagnostic test. . Don't order a Tzanck test to diagnose HSV infection; it is neither sensitive nor specific. o Recurrent erythema multiforme is most commonly caused by HSV recurrences. Treatment For the first episode oforal or genital herpes, treat with acyclovir, : famciclovir, or valacyclovir for 7 to 10 days. Recurrent infection can be managed with either episodic self start therapy or long ! term suppressive therapy. Perianal Herpes Slmplex: Perianal herpes simplex in an immunocompromised t patient (HIV/AIDS). ln patients with HIV disease, herpes simplex may appear as painful, shallow ulcers rather than the classic vesicle. L DON'T BE TRICKED L o Do not treat herpetic keratitis with topical glucocorticoid drops . Topical acyclovir is not elTective for treating genital herpes. t t L I Syphilis L

Treatment For the first episode oforal or genital herpes, treat with acyclovir, : famciclovir, or valacyclovir for 7 to 10 days. Recurrent infection can be managed with either episodic self start therapy or long ! term suppressive therapy. Perianal Herpes Slmplex: Perianal herpes simplex in an immunocompromised t patient (HIV/AIDS). ln patients with HIV disease, herpes simplex may appear as painful, shallow ulcers rather than the classic vesicle. L DON'T BE TRICKED L o Do not treat herpetic keratitis with topical glucocorticoid drops . Topical acyclovir is not elTective for treating genital herpes. t t L I Syphilis L t Diagnosis Primary syphilis presents as an ulcer (chancre). The ulcer has a clean appearance with heaped-up borders, is usually painless, t and resolves spontaneously. t Secondary syphilis develops 2 to 8 weeks after the appearance of the chancre. Secondary syphilis resolves spontaneously. L I To diagnose secondary syphilis, look for: L I I L . fever and any type of rash (except vesicles), often with palmar or plantar involvement f r nontender generalized lymphadenopathy I o mucous patches (slightly elevated oval oral erosive lesions with surrounding inflammation) I o condylomata lata lesions (gray to white, raised, wart like lesions on moist intertriginous surfaces) I t Latent (tertiary) syphilis involves the presence of serologic evidence of infection in the absence of clinical signs' Latent syphilis L is divided into early latent (infection <1 year in duration) or late latent (infection >1 year). If duration is unknown, it is classified l as latent syphilis of unknown duration. L I I 241 L I