568 What every doctor should know about HIV An expert should manage patients with HIV infection . HIV in developed countries is primary management of antiretroviral drugs and their toxici ties and controlling HIV viral load \200\224not opportunistic infections. Preventing HIV spread Screen patients for high-risk behavior and reduce barriers to safer s ex: Pro- mote lifelong safer sex, barrier contraception, and reduction in the num- ber of p artners. Videos followed by interactive discussions are one way to double the use of condom s. Another way is the 100% condom program involving distribution of condoms to brothels, wi th enforcement programs enabling monitoring and encouraging condom use at any sex establish ment. Such programs are estimated to have prevented 2 million HIV infections in Thailand. T esting enhances counseling, partner notification, and early treat- ment. Warn everyone abou t the dangers of sexual tourism/promiscuity. Tell drug users not to share needles. Use need le exchange programs. Vigorous control of other STIs can reduce HIV incidence. Strengthen a wareness of clinics for STIs. Encourage pregnant women to have HIV tests. (Cesarean section s and HAART during pregnancy can prevent vertical transmission). All HIV-infected persons s hould have partner notification. Think about acute seroconversion: The clinical features ar e similar to infec- tious mononucleosis; perform tests if there are unusual signs; e.g., or al can- didiasis, recurrent shingles, leucopenia, or CNS signs (antibody tests may be negat ive, but HIV RNA levels are elevated in early infection). As always, take a thorough histor y. If you do identify acute seroconversion illness, get expert help promptly. Counseling to prevent HIV transmission is critical. Occupational exposure and needle-stick injury Seroco nversion rates are 0.4% for HIV, 30% for hepatitis B, if HBeAg positive and recipient is u nvaccinated, and 1.9% for hepatitis C. Wash wound well; do not suck or immerse in bleach. N ote name, address, and clinical details of source patient. Report incident to Occupational Health and fill out an accident form. Rapid HIV test should be performed on source if HIV s tatus is unknown. Informed consent in a source patient is sometimes required for HIV serol- ogy. Also test source for HBV (HBsAg) and HCV (anti-HCV). Immunize (active and passive) ag ainst hepatitis B at once, if needed. Counsel injured person that HIV risk <0.5% if source is HIV positive and test recipient at baseline 3, 6, 12 months (seroconversion may take t his long). Weigh risks, which are based on the viral load in the source patient and the sev erity of injury to the health care worker, volume of blood on instru- ment, and depth of in jury. Higher risk exposures include source patients with symptomatic HIV, acute seroconvers ion, and viral load >1,500 and deeper injuries with needles that have hollow bores, were us ed in an artery or vein and/or have visible blood. Higher risk exposures should be treated with three or more antiretroviral drugs. Lower risk exposures include source patients who a re asymptomatic and have a viral load <1,500 and superficial injuries with solid needles/in struments. These may be treated with a two- drug regimen. Mucus membrane or nonintact skin exposure carries a lower risk. If fluid volume is high and source patient is high risk, use three or more drugs. Otherwise consider two drugs, or none in the case of low-risk source patient and low fluid volume exposure. HIV test counseling: If in doubt, get help from an H IV care center. Routine tests in the recipient are HIV serology at baseline, 6 wks, 3 month s, and 6 months. Viral load to detect acute infection should not be done unless symptomatic . Routine tests in the donor are rapid HIV serology, anti-HCV, and HBsAg if these have not been done previously. For assistance in testing and selection of therapy, health care worke rs can call PEPline at 888 \200\223448 \200\2234911. s e s a e s i d s u o i t c e f n I 569 Table 14.28 Prophylaxis and treatment of opportunistic infections Infection Pneumocystis jiroveci (PCP) Prophylaxis TMP/SMX DS/d, TMP/ Indication Start: CD4<200, oropha- ryngeal candidiasis, h/o PCP SMX SS/d, TMP/SMX DS/thrice weekly Dapsone 100 mg/d, Stop: CD4 count >200 Dapsone 50 mg/12 h, Dapsone 50 mg/d + pyrimethamine 50 mg/d + folinic acid 25 mg/d, atovaqu one 1,500 mg/d, atova- quone 1,500 mg/d + pyrimethamine 25 mg/d + folinic acid 10 mg/d, aer osolized pentamidine 300 mg/month. Screen for G6PD defi- ciency before giving dapsone for >3 months Mycobacterium avium (MAI) Azithromycin 1,200 mg/w, Azithromycin 600 mg/ twice weekly, clarithro- mycin 500 mg/12 h TM P/SMX DS/d, TMP/ Start: CD4<50 Stop: CD4>100 for \200\234 3 months Toxoplasmosis Start: Toxo IgG + and SMX SS/d, dapsone 50 mg/d + pyrimethamine 50 mg/d + folinic acid 25 mg/d, atovaquone 1,500 mg/d ( pyrimethamine 25 mg/d + folinic acid 10 mg/d CD4 <100 Stop: CD4 count >200 for >3 months Screen for G6PD deficiency before giving dapsone Tuberculosis See TB section Screen for and treat latent TB Coccidioido- mycosis Fluconazole 400 mg/d Itraconazole 300 mg/12 h CD4<250 and + IgM or IgG to cocci and from and endemic area 570 Infection PCP Treatment Moderate to Severe : TMP (5 mg \200\223kg)/SMX (25 mg/ kg)/6 \200\2238 h, pentami dine 3 \200\2234 mg/kg/24 h, primaquine 15 \200\22330 mg/24 h + clindamycin 600 \200\223900 mg/8 h IV (or 300 \200\223450 mg/6 \200\2238 h PO) \227 21 d Hypoxemia: Room air PaO 2 <70 or Aa gradient >35: Add prednisone 40 mg/12 h \227 5 d then 40 mg/d \227 5 d then 20 mg/d \227 11 d Mild to moderate: TMP/SMX as above or TMP/SMX DS 2 tab tid, Dapsone 100 mg/d + TMP 5 mg/kg/ 8 h, primaquine 15 \200\22330 mg/d + clindamycin 300 \200\223450/6 \200\2238 h PO, atovaquo ne 750 mg/12 h \227 21 d Check G6PD before giving Primaquine s e s a e s i d Table 14.28 (Continued) Disseminated Clarithromycin 500 mg/12 h (or azithromycin 500 \200\223600 mg/d) + ethambutol 15 mg/kg/d rifabutin 300 mg/d. Treatment is continued until sustained immune recovery MAI s u o i t c e f n I Toxoplasmosis Induction: <60 kg: Pyrimethamine 200 mg \227 1 then 50 mg/d + sulfadiazine 1,000 mg/6 h + folinic acid 10 \200\22350 mg/d \227 6 wks >60 kg: Pyrimethamine 200 mg \227 1 then 75 mg/d + sulfadiazine 1,500 mg/6 h + folinic acid 10 \200\22350 mg/d \227 6 wks Maintenance : Pyrimethamine 25 \200\22350 mg/d + sulfa- diazine 1,000 mg/6 \200\22312 h + folinic acid 10 \200\22325 mg/d. Treatment is continued u ntil sustained immune recovery. Clindamycin 600 mg/6 h can be used in place of sulfadiazine . Adjunctive steroids may be needed to control CNS edema. Oropharyngeal candidiasis Fluconazole 100 mg/d, clotrimazole 10 mg troches/4 \200\2235 h, nystatin suspension 4 \200\2236 m L /6 h \227 7 \200\22314 d Esophageal Fluconazole 100 \200\223400 mg/d IV or PO, itraconazole candidiasis 200 mg/d PO, voriconazole 200 mg/12 h IV or PO, posaconazole 400 mg/12 h PO, echinocandin ( e.g., caspofungin, micafungin, anidulafungin) IV Cryptococcosis Induction: Deoxycholate amphotericin B 0.7 mg/kg/d IV or lipid amphotericin B 4 \200\2236 mg/kg/d IV + flucyto- sine 25 mg/kg/6 h \227 2 wks or longer Consolidation : Fluconazole 400 mg/d \227 8 wks Maintenance: Fluconazole 200 mg/d. Treatme nt is continued until sustained immune recovery. Follow flucytosine levels See TB section Induction : Ganciclovir implant + valganciclovir 9 00 mg/12 h PO, ganciclovir 5 mg/kg/12 IV, foscarnet 60 mg/8 h IV or 90 mg/12 h IV \227 14 \200\22321 d, cidofovir 5 mg/ kg/wk \227 2 then every other week (give with saline and pro benecid) Maintenance : Valganciclovir 900 mg/d, ganciclovir 5 mg/kg/d, foscarnet 90 \200 \223120 mg/kg/d, cidofovir 5 mg/kg/ every other week (give with saline and probenecid) Tuberculosis CMV retinitis 571 Treatment and monitoring of patients with HIV infection Extensive, long-term studies involv ing clinical end points such as death consistently show extraordinary benefit with antiretr oviral therapy (ART). Mortality, AIDS rates, and hospitalization rates are reduced by 60 \200\22380%. Goals of therapy: Reduce morbidity, prolong survival, improve immune func- tio n, suppress viral load, and prevent transmission. Indications to start ART: Able to commit to taking medications for life and any of the belo w: \212 AIDS-defining illness (especially with opportunistic infection and viral load >100,000 copi es/m L ) CD4 count <500 (particularly important in <200 rapidly declining CD4 counts) HIV-a ssociated nephropathy Hepatitis B co-infection (when treatment of hepatitis B is indicated) Pregnant women (to prevent perinatal transmission) \212 \212 \212 \212 Consider ART in patients with CD4 count >500 Consider a brief delay in in itiating ART in cases of cryptococcosis and non- tuberculous mycobacteria infections (to re duce chance of immune recon- stitution syndrome). Check viral load at initiation or modific ation of ART and 2 \200\2238 wks later. If still detectable, recheck every 4 \200\2238 wks until <200 copies/m L Virological failure is an inability to achieve or maintain viral load <200. Baseline tests: HIV serology, viral load and genotype CBC, CD4 count, chemistry prof ile, liver function tests, lipids, CXR, U/A, toxoplasmosis serology, G6PD (in appropriate r isk groups), PPD or IGRA, Pap smear, HAV (total Ab), HBV (HBsAg, and antibody to HBs or HBc ), HCV (anti- HCV), syphilis and other STIs, consider CMV IgG. Special tests: HLA-B*5701 (p rior to giving abacavir) and co-receptor tro- pism assay (prior to giving CCR5 entry inhibi tor) Monitoring: Every 3 \200\2236 months: CBC, CD4 count and viral load. Every 6 \200\2231 2 months: Basic chemistries, liver function tests HIV treatment The major concerns with HAA RT are: \212Virologic failure , which may be due to multiple factors including poor adherence, antiviral resistance and suboptimal antiviral potency Adverse effects \212 What to start (initial regimen): \212 \212 of the drugs, both short- and long-term Efavirenz /tenofovir /emtricitabine (EFV/TDF/FTC) Ritonavir-boosted atazanavir + tenofovir/ emtricitabine (ATV/r + TDF/ FTC) Ritonavir-boosted darunavir + tenofovir/emtricitabine (DRV /r + TDF/ FTC) Raltegravir + tenofovir/emtricitabine (RAL + TDF/FTC) \212 \212 Note: Choice of regimen should be individualized based on patient prefer- ence, side- effect profile, patient \200\231s comorbid conditions and other medica- tions, and baseline antiviral resistance profile. Ritonavir is used to boost levels of protease inhibitors. (S ee DHHS Guidelines: www.aidsinfo.nih. gov.) Antiviral agents An HIV expert should supervise all HIV treatment. Classes of drugs are nucleoside reverse transcriptase inhibitors (NRTI) , non-nucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitors (PI), integra se inhibi- tors, and viral entry inhibitors. General principle of initial therapy is to com bine two NRTIs with an NNRTI, a boosted PI, or integrase inhibitor. Nucleoside analog rever se transcriptase inhibitors (NRTI) \212Zidovudine (Azidothymidine, AZT) was the first anti -HIV drug. Dose: 300 mg/12 h or 200 mg/8 h PO. SE: Anemia, leucopenia, gastrointestinal 572 disturbance, lactic acidosis. AZT requires dosage adjustment in renal dysfunction. s e s a e s i d \212 Didanosine (DDI; Videx ec ) Dose: 250 mg/24 h PO if wt <60kg; 400 mg/24 h if >60 kg. SE: Pancreatitis, lactic acidosis, peripheral neuropa- thy, GI disturbance. Stop treatment if significant rise in amylase. Take on empty stomach. DDI requires dosage adjustment with concomitant TDF use, renal dysfunction. s u o i t c e f n I \212Lamivudine (3TC) is probably the best-tolerated antiretroviral. Dose : 150 mg/12 h or 300 mg QD PO. SE : With HBV co-infection there may be flare in hepatitis with HBV resistanc e, immune reconstitution or flare if 3TC is stopped. 3TC requires dosage adjustment with re nal dysfunction. \212 Stavudine (D4T) Dose: 40 mg/12 h PO if >60 kg; 30 mg/12 h PO if <60 kg. Need to stop treatment if peripheral neuropathy, lipoatrophy, hypertriglyceridemia, pan creatitis, lactic acidosis. D4T requires dosage adjustment in renal dysfunction. \212Tenofovir (TDF) Dose : 300 mg/24 h PO. SE : Rare causes of renal failure including Fan coni syndrome and ABV flare if TDF stopped. Give with care in renal dysfunction and require s adjustment. \212Abacavir (ABC) Dose : 300 mg/12 h or 600 mg qd PO. SE : Hepatitis, hypersensitivity sy ndrome (5 \200\2238%): Rash, fever, vomiting; may be fatal if rechallenged; highest risk in those with HLA-B*5701, so screen before giving drug. \212Emtricitabine (FTC) Dose : 200 mg/24 h PO. SE: Same as lamivudine. FTC can cause hyper pigmentation/skin discoloration and requires adjust- ment with renal dysfunction. Protease inhibitors (PI): PIS are often given with low-dose ritonavir (200 \200\223400 mg/d PO), which enhance drug levels except with nelfinavir (NFV). All PIs are metabolized by th e cytochrome P-450 enzyme system. They may there- fore increase the concentrations of certa in drugs by competitive inhibition of their metabolism if administered concomitantly. Also, PI levels can be altered by other medications that impact CYP metabolism. PIs associated w ith body fat redistribution: Increased abdominal fat, breast enlargement, and a buffalo hum p. Other class specific SE : Hyperlipidemia, hyperglycemia, insulin resistance, and gastroi ntestinal disturbance. ATV does not alter lip- ids or cause insulin resistance. \212 Indinavir (IND) Dose: 800 mg/8 h or IND/r 800/100 \200\223200 mg/12 h PO, 1 h before or 2 h after a meal. SE : Dry mouth, taste disturbance, pruritus, alopecia, increased LFT and nep hrolithiasis Saquinavir (SQV) Dose: SQV/r \200\2241,000/100 mg bid PO. SE: GI intoler- ance s, rash, hepatitis, lipodystrophy, and paresthesiae Nelfinavir (NFV) diarrhea, increased CK Lopinavir/Ritonavir (LPV) (Kaletra ) Dose : 400 mg (+ 100 mg ritonavir)/ bid PO. LPV can be used as 800 mg/200 mg/d in some patients. SE: GI intolerances, rash, hepatitis, and lipo dystrophy Atazanavir (ATV) Dose : 400 mg qd with food or with RTV 300 mg/100 mg qd with foo d. SE: Hyperbilirubinemia (benign), GI intolerance, and neph- rolithiasis ( Note : Does not cause hyperlipidemia or insulin resistance.) Dose adjustment needed in patients taking efa virenz, H 2 antagonists, and proton pump inhibitors Tipranavir (TPV) Hepatotoxicity, rash, GI intolerances, CNS bleed (rare) Fosamprenavir (FPV) 700 mg/100 bid. SE: Rash, lipodystrop hy, GI intolerance Darunavir ance, hepatitis, and lipodystrophy, rash with Stevens-Johnson \212 \212 Dose : 1,250 mg/12 h or 750 mg/8 h PO. SE: Hepatitis, \212 573 \212 \212 Dose : With RTV 500/200 mg bid only for salvage. SE: \212 Dose : 1,400 mg/12 h, FPV/r 1,400/100 \200\223200 mg/d or \212 Dose : With RTV 800/100/d or 600/100 mg bid. SE: GI intoler- Non-nucleoside reverse transcriptase inhibitors (NNRTI): These may interact with drugs meta bolized by the cytochrome P-450 enzyme system, which they either induce or inhibit dependin g on the concomitantly administered drug. \212 Nevirapine (NVP) Dose : 200 mg/24 h for 2 wks, then 200 mg/12 h or 400 mg-XR/24 h PO. Resis tant mutants emerge readily. SE: Stevens \200\223Johnson syndrome, toxic epidermal necrolys is, hepatitis including fatal hepatic necrosis \212Efavirenz (EFV) Dose : 600 mg/24 h PO. SE: Rash, sleep disturbance, hepa- totoxicity, neuropsychiatric symptoms, dizziness in first 2 \200\2233 wks. Avoid in pregnancy due to te ratogenicity (category D) Etravirine (ETR) drome, hepatotoxicity Rilpivirine (RPV) Dose: 25 mg/24 h PO. SE: Rash, insomnia, depression, headache \212 Dose : 200 mg/12 h PO. SE: Rash, Stevens-Johnson syn- \212 Others: \212 Raltegravir (RAL)Integrase inhibitor. 800 mg/12 h if taken with rifampin). SE: GI intoleran ce, CPK elevation Enfuvirtide (T20) Fusion inhibitor. injection site reactions seen in almo st all patients Maraviroc (MVC) Entry inhibitor. concomitant medications). SE: GI intoleran ce, hepatotoxicity Dose : 400 mg/12 h PO (increase to \212 Dose : 90 mg (1 m L ) SQ/12 h. SE: Local \212 Dose : 150 \200\223600 mg/bid(depending on Golden rules for HAART \212 Start HAART early, ideally before opportunistic infection or malignancy and with CD4 count well above 200. Establish a trusting relationship with the patient. Explain to patients tha t regimens are complex and stress the importance of strict adherence. Use a multidisciplina ry team to identify and address barriers to adherence (e.g., social, psychiatric, economic, and substance abuse-related). Use multiple anti-HIV drugs (minimizes replication and resis tance) together (see above for recommended regimens). Monitor plasma viral load and CD4 cou nt. Aim for undetectable viral loads (<50 copies/m L ) within 4 \200\2236 months of startin g HAART. Suspect poor adherence or transmitted resistance if viral load rebounds. Assess ad herence to regimen at every clinic visit. If virologic goals are not achieved, the cause is resistance or failure of drug to reach target (usually due to nonadherence, but possibly d ue to drug interactions, food effect, etc.). The usual reasons to change therapy are toxici ty or virologic failure. 1 If toxicity: Substitute for the implicated drug. 2 If viral fail ure: Review adherence and drug interactions, etc. Changes in \212 \212 \212 \212 \212 \212 \212 574 regimen are then made based on genotypic resistance tests. \212 \212 HIV therapy continues to evolve rapidly. Keep up with published guidelines and advisories. Sexually transmitted infections Incidence Although great progress has been made in the past decade in treating STIs, they still remains a major health problem. Chlamydia remains the most commonly reported infectious disease in the United States, with nearly 1.3 million cas es in 2010. Additionally, there are >310,000 cases of gonorrhea and nearly 14,000 cases of syphilis reported annually. African Americans, especially women, are disproportionately aff ected by Chlamydia and gonorrhea. MSM and African Americans are most affected by primary an d secondary syphilis. Presentation Many are asymptomatic, which facilitates transmission. Therefore, screening is critical. When symptomatic, presentations include vaginal or urethral discharge, genital l esions, pelvic infection, cervical neoplasia, HIV disease, and ectopic parasites. History A sk about partners (number, gender), practice (vaginal, oral, anal), protection (condoms), a nd past history of STI. Examination Detailed examination of genitalia including inguinal no des and pubic hair, scrotum and male urethra, rectal examination, pelvic and speculum exami nation. Overview of tests Refer to STD clinic. Urine: Dipstick and culture for GC and C. tr achomatis . Ulcers: Take swabs for HSV culture (viral transportation medium). Dark field mi croscopy for syphilis ( T. pallidum ) requires expertise. Men: Urethral smear for Gram stai n and culture for N. gonorrhoeae (send quickly to lab in Stuart \200\231s medium); urethral swab for Chlamydia . Women: High vaginal swab in Stuart \200\231s medium for microscopy an d stain for Candida , Gardnerella vaginalis , anaerobes, Trichomonas vaginalis ; endocervic al swab for Chlamydia trachomatis . Chlamydia (an obligate intracellular bacterium) is usua lly asymptomatic but easy to detect with urinary nucleic acid amplification tests (NAAT) te st. Blood tests: Syphilis, herpes type-specific antibodies, hepatitis B and C, and HIV sero logy. Follow-up Arrange to see patients at 1 wk and 3 months, with repeat smears, cultures, and syphilis serology. Patients should avoid sex until treatment is completed. Partners sh ould be referred for screening and treatment. If the partner is unlikely to present for tre atment, consider giving the treatment course for the partner to deliver to the patient. Not e: This may be prohibited in some states. Screening programs in asymptomatic patients can r educe complications (e.g., infertility, PID) and reduce transmission. Patients seeking trea tment for STD, commercial sex workers, drug users, and sexual contacts of persons with STD require aggressive and frequent screening for multiple infections. See Table 14.29. Ectopar asites Scabies ( Sarcoptes scabiei ): Spread is common in families. Presentation: Papular r ash (on abdomen or medial thigh; itchy at night) + burrows (in digital web spaces and flexo r wrist surfaces). Incubation: 6 wks (during which time sensitization to the mite \200\231 s feces and/or saliva occurs). Penile lesions produce red nodules. Diagnosis: Tease a mite out of its burrow with a needle for microscopy. This may fail, but if a drop of oil is plac ed s e s a e s i d s u o i t c e f n I Lactobacillus , Table 14.29 Routine screening recommendations Population Men who have sex with men Pregnant women Infection Annually: G C, Chlamydia , HIV, syphilis, con- sider anal Pap screening First tri mester: G C, Chlamydia , HIV, hepati- 575 tis B surface antigen, and syphilis Sexually active women Annually: G C and Chlamydia HIV at least once Annually: G C, Chlamydia , syphilis; in women < 25 HIV-positive also check trichomoniasis Women >25 and het- erosexual men Routine screening not recommended, but testing should be considered in higher risk situations (e.g., multiple partners, African Am erican women up to age 30, and prior STD) on the lesion, a few scrapes with a scalpel may provide feces or eggs. Treat the entire hou sehold. Give written advice. Apply permethrin 5% cream to entire body (from neck down) and wash off in 8 \200\22314 h. Oral therapy with ivermectin 200 mcg/kg \227 1 and repeated in 2 wks is another option. Pediculosis pubis: Often spread via sexual transmission. Presenta tion: Itching, visible lice or nits. Treatment: Permethrin 1% cream or pyrethrins applied t o affected area; wash off after 10 minutes. and Lymphogranuloma ulceration. Causes: Lymphog ranuloma venereum , chancroid ( Haemophilus ducreyi ), or granuloma inguinale ( Calymmatoba cterium granulomatis [i.e., donovanosis]). The latter causes extensive, painless, red genit al ulcers and pseudobuboes (i.e., abscesses near inguinal nodes), with possible elephantias is malignant change. Diagnosis: \200\234Closed safety-pin \200\235 inclusion bodies in cytoplasm of histiocytes. Treatment: Doxycycline 100 mg/12 h PO until all lesions epithelia lized (at least 3 wks); alternatives include azithromycin, erythromycin, ciprofloxacin, or TMP/SMX. Genital, anal or perianal ulcer disease Usual cause is HSV, syphilis, or both. His tory and physical exam must be backed up with laboratory confirma- tion. In the United Stat es, there are 50 million people with genital herpes. Most are due to HSV \200\2232 and ar e asymptomatic. In young women and MSM, HSV \200\2231 is increasingly associated with anoge nital ulcers. HSV \200\2232 is more likely to recur than HSV \200\2231. When symptomatic, H SV infection can present as painful vesicles or ulcers. Diagnosis is with culture, PCR, ser um HSV2 serology. See HSV section for treatment. Syphilis is a systemic infection with pote ntially overlapping stages. Primary: A macule at site of sexual contact becomes a very infe ctious, painless, hard ulcer (primary chancre). Secondary: Occurs 4 \200\2238 wks after the chancre. Manifestations include fever, malaise, lymphadenopathy, rash (trunk, face, palms, soles), alopecia, mucocutaneous lesions, buccal snail- track ulcers; rarely hepatitis, men ingitis, nephritis, uveitis. Tertiary syphilis follows 2 \200\22320 yrs latency (when patie nts are noninfectious). There are gum- mas (granulomas occurring in skin, mucosa, bone, joi nts, rarely viscera, e.g., lung, testis). Quaternary syphilis: Ascending aortic aneurysm aortic regurgitation; cranial nerve palsies; stroke; dementia; psychoses; sensory ataxia; numb legs, chest, and bridge of nose; lightning pains; gastric crises; reflex loss; extenso r plantars; Charcot \200\231s joints; and Argyll Robertson pupil. Latent infection refers t o serological evidence of syphilis without symptoms. Note that neurological infection , whi ch can occur throughout the course of untreated syphilis, can present as meningitis, stroke s, visual and hearing loss, and a range of potentially devastating neuropsychiatric abnorma lities. Inguinal lymphadenopathy Presentation: Syphilis serology (Two types): Cardiolipin antibody: Not treponeme-specific. Indicates acti ve disease and becomes negative after treatment. These are useful for screening and to de- termine response to therapy. For initial diagnosis, a positive test should be followed up b y a confirmatory treponemal test. False positives (with negative treponemal antibody) can o ccur with pregnancy, immunization, pneumonia, malaria, SLE, TB, leprosy, HIV. Examples: Ven ereal disease research labora- tory (VDRL) slide test, rapid plasma reagin (RPR), Wasserman n reaction (WR). Treponeme-speci \201 c antibody: Positive in primary disease, remains so despite treatment. Examples: Fluorescent treponemal antibody (FTA \200\223ABS), EIA, T. pal lidum hemagglutination assay (TPHA), T. pallidum immobilization (TPI) test. Other tests : I n primary syphilis, treponemes may be seen by dark field mi- croscopy of genital chancre fl uid; serology at this stage is often negative. Interpretation of dark field microscopy requ ires expertise. In secondary syphilis, treponemes are seen in the lesions, and both types o f antibody 576 s e s a e s i d Table 14.30 Treatment of syphilis Scenario Primary secondary: Treatment Benzathine PCN-G 2.4 million units IM \227 1 dose PCN allergic: Doxycycline 100 mg/12 h or tetra- cycline 500 mg/6 h \227 14 d Benzathine PCN-G 2.4 million units IM \227 1 dose or s u o i t c e f n I Latent (<12 months from exposure) Latent (>12 months or unknown time from exposure) Benzathine PCN-G 2.4 million units IM weekly \227 3 wks PCN allergy: Doxycycline 100 mg/12 h or tetra- cycline 500 mg/6 h \227 28 d Neurosyphilis and tertiary syphilis PCN-G 3 \200\2234 million u/4 h or continuous IV \227 10 \200\22314 d PCN allergy: Consider desensitization to PCN or ceftriaxone 2 g/d IV or IM \227 10 \200 \22314 d, but beware of cross-reactions Beware of Jarisch \200\223Herxheimer reaction: Fever, tachycardia, and vasodilatation hours after the first dose of antibiotic. Commonest in secondary disease; most dangerous in tert iary disease. Consider steroids. tests are positive. In late syphilis, organisms may no longer be seen, but both types of an tibody test usually remain positive (cardiolipin antibody tests may wane). In neurosyphilis , CSF VDRL may be positive, but false negatives are common. Consider chancroid in settings where H. ducreyi is prevalent (e.g., sporadic outbreaks, and in parts of Africa and the Car ibbean). Presentation : Painful ulcer, suppurative inguinal adenopathy. Diagnosis : Culture . Treatment : Azithromycin 1 g \227 1, ceftriaxone 250 mg IM \227 1, ciprofloxacin 500 mg /12 h \227 3 d, erythromycin 500 mg/8 h \227 7 d. See Table 14.30. Vaginal discharge and urethritis Some vaginal discharge may be physiologic. Most discharges associated with foul odor and itching are due to infection. A very foul discharge may be d ue to a foreign body (e.g., forgotten tampons). Discharges rarely resemble their classical descriptions. Vaginal yeast infection (Candida albicans) This is the most common cause of p athological discharge and is classically described as white curds. The vulva and vagina may be red, fissured, and sore. This is not an STD, so partner treatment is unnecessary. Risk factors: Pregnancy, immunodeficiency, diabetes, birth control pills, and antibiotics. Diagn osis: Microscopy: Strings of mycelium or oval spores. Culture on Sabouraud \200\231s medium is rarely indicated except to test in vitro sensitivity in refractory cases. Treatment: Mu ltiple topical azoles are available and (e.g., miconazole, butoconazole, and clotrimazole) can be obtained without a prescription. A single dose of fluconazole 150 mg PO is an altern ative. Reassure that vulvovaginal candidiasis is not sexually transmitted. Trichomonas vagi nalis (TV) Produces vaginitis and a thin, bubbly, fish-smelling discharge. It is sexually t ransmitted. Exclude gonorrhea (which may coexist). The motile flagellate may be seen on wet movie microscopy or cultured. Treatment: Metronidazole or tinidazole 2 g PO \227 1 or met ronidazole 500 mg/12 h PO for 7 d. Treat the partner. 577 Bacterial vaginosis presents with fish-smelling discharge. The vagina is not inflamed, and itch is common. Vaginal PH is >5.5, resulting in alteration of bacterial flora overgrowt h (e.g., of Gardnerella vaginalis , Mycoplasma hominis, Mobiluncus, and anaerobes, such as Bacteroides spp.) with too few lactobacilli. There is increased risk of preterm labor and a mniotic infection if pregnant. Diagnosis: Stippled vaginal epithelial \200\234clue cells \200\235 may be seen on wet microscopy. Treatment: Metronidazole 500 mg/12 h PO for 7 d, me tronidazole or clindamycin cream. Gonorrhea ( Neisseria gonorrhea ; gonococcus, GC) infect any columnar epithelium (e.g., urethra, cervix, rectum, pharynx and conjunctiva). Incubatio n: 2 \200\22310 d. Symptoms: Purulent urethral discharge, dysuria, proctitis, tenesmus, pha ryngitis, vaginal discharge; many patients are asymptomatic. Complications \200\224Local: P rostatitis, cystitis, epididymitis, salpingitis, bartholinitis. Systemic: Septicemia; e.g., with petechiae, hand/ foot pustules, arthritis; Reiter \200\231s syndrome; endocarditis (r are). Long-term: Urethral stricture, infertility. Diagnosis: Gram stain, culture of relevan t specimen, nucleic acid amplification test. Treatment: Uncomplicated infection: Ceftriaxon e 250 mg IM \227 1. Cefixime 400 mg \227 1 is another option but does not cover pharyngea l disease well. Treat for Chlamydia too (e.g., doxycycline 100 mg/12 h PO for 7 d, or a sin gle dose of azithromycin 1 g PO) as 50% of patients with urethritis or cervicitis will have concomitant C. trachomatis infection. Trace contacts. No intercourse or alcohol until cure d. Nongonococcal urethritis is commoner than GC. Discharge is thinner and signs less acute, but this may not help diagnosis. Women (typically asymptomatic) may have cervicitis, ureth ritis, or salpingitis (pain, fever, infertility). Rectum and pharynx are not infected. Orga nisms: C. trachomatis (nucleic acid amplification tests can detect this), Ureaplasma urealy ticum , Mycoplasma genitalium , Trichomonas vaginalis , Gardnerella , gram-negative and ana erobic bacteria, Candida . Complications: Similar to local complications of GC. Chlamydia m ay cause Reiter \200\231s syndrome and neonatal conjunctivitis. Treatment: Azithromycin 1 g \227 1 or doxycycline 100 mg/12 h PO. Trace contacts. Avoid intercourse during treatment and alcohol for 4 wks. Noninfective urethritis Traumatic, chemicals, cancer, foreign body. can Infections associated with animal contact Bites Most common bite is from dogs (about 80%). Typical organisms in dog and cat bites are oral flora from animal ( Pasteurella, Capnocytop haga, Porphyromonas, Bacteroides, and S. aureus ) and human skin flora. Approach: Cleanse w ound, update tetanus vaccination, and give antibiotics for all obviously infected wounds an d for all human bites, all wounds that are moderate to severe, associated with edema, at ha nds or near a bone or joint, and in immunocompromised patients. Infected wounds should not be closed. Empiric therapy: Amoxicillin 500 mg/clavulanate 875 mg/12 h PO, ampicillin/sulba ctam 1.5 \200\2233 g/6 \200\2238 h IV. History of contact with speci \201 c animals can be helpful: Rabbits ( Francisella tularensis -tularemia), kittens ( Bartonella henselae: Cat scratch disease), parturient cats ( Coxiella burnetii : Q fever), cat litter (toxoplasmosis ), sick cats and wild rodents ( Yersinia pestis ), birds ( Salmonella, Chlamydia psittaci, Cryptococcus neoformans ), reptiles ( Salmo- nella species ), raccoons ( Baylisascaris ), b at guano (histoplasmosis), rodents including pets (lymphocytic choriomeningitis virus,) wil d mice (hantavirus), macaque monkeys (herpes B), farm animal and petting zoos ( E. coli 015 7:H7, Campylobacter, cryptosporidiosis), fish tanks ( Mycobacterium marinum ). Rabies is a rhabdovirus spread by bites from any infected mammal. Most common rabid species in the Unit ed States are raccoons, skunks, bats, foxes; beware of contact with rabid dogs and cats (es pecially with travel 578 outside the United States). Nearly all cases in the United States are from bat bites (bewar e of any exposure; bat bites may be unapparent); nearly all in developing world are dog bit es. Incubation is usually 9 \200\22390 d, so give prophylaxis even several months after exp osure. Prodrome symptoms include headache, malaise, abnormal behavior, agitation, fever, an d itching at the site of the bite. Disease progresses to \200\234furious rabies \200\235; e.g., with water provoking muscle spasms and may be accompanied by profound terror (hydroph obia). In 20%, \200\234dumb rabies \200\235 starts with flaccid paralysis in the bitten li mb and spreads. Treatment if bitten where rabies is endemic (if unvaccinated): Seek expert help. If bite is from a domestic dog, cat, or ferret, the animal can be ob- served for 10 d . If bite is from skunk, raccoon, fox, or bat, the animal can be euthanized and tested. If this is not possible, give postexposure prophylaxis (previously not vaccinated); wound clea nsing, human rabies immune globu- lin (HRIG) 20 IU/kg, give as much as possible into wound, give rest IM + vaccine (HDCV or PCECV)1.0 m L IM (not HRIG site) on days 0,3,7,14. For tho se previously vaccinated, give IM vaccine at day 0 and 3 and no HRIG. Pre-exposure prophyla xis (e.g., veterinarians, zoo-keepers, customs officials, bat handlers, and certain travele rs): Give three doses of vaccine IM (days 0, 7, 21 \200\22328). Rabies is usually fatal onc e symptoms begin, but survival has been docu- mented in a handful of patients. A neuroprote ctive protocol is available through Children \200\231s Hospital of Wisconsin. s e s a e s i d s u o i t c e f n I Miscellaneous gram-positive bacteria Staphylococci When pathogenic, these are usually eithe r S. aureus or co- agulase - negative Staphylococci (CONS). Typically, S. aureus cause loca lized infection of skin, lids, or wounds, as well as invasive bloodstream and deep tissue i nfections. Severe infections with S. aureus include pneumonia, osteo- myelitis, septic arth ritis, endocarditis, and septicemia. S. aureus toxins may cause food poisoning (or the toxi c shock syndrome toxin [TSST \200\2231]). The latter presents as shock, confusion, fever, r ash with desquamation of digits, diarrhea, myalgias, CPK elevation, and thrombocytopenia an d is associated with colonization or infection by toxin-producing staphylococci. CONS are t he most common cause of bloodstream infections in hospitalized pa- tients and important cau ses of medical device-associated infections. When isolated from a culture, CONS are frequen tly contaminants. Up to 80% of CONS in blood cultures are contaminants. Clues to actual inf ection are recovery from a normally sterile site in the appropriate clinical context. Methi cillin-resistant S. aureus (MRSA) is a major issue in health care system- acquired and comm unity-acquired infection, causing pneumonia, septicemia, wound infections, and deaths. In t he United States, about 50% of nosocomi- al S. aureus infections are MRSA. Management of he alth care system MRSA: The usual drug is vancomycin; more recently, linezolid and daptomyci n have been introduced. All three are essentially universally active against MRSA. However, daptomycin should not be used in cases of pneumonia as it is inactivated by surfactant. Co mmunity-acquired MRSA (USA 300 strain) has emerged as an important cause of skin and soft-t issue infection. Such staph- ylococcal infections are due to strains that are clonal, globa l, and harbor genes for the Panton-Valentine leukocidin that is associated with virulence. These strains usually harbor the mec IV element that confers resistance to \222 -lactams. Sensitivity tests usually show susceptibility to clindamycin, doxy- cycline, gentamicin, an d TMP/SMX. The most common infections are large furuncles that require surgical drainage. O ther less common infections are necrotizing fasciitis, necrotizing pneumonia, and pyomyosit is. Management: Simple cutaneous abscess require drainage, and antibiotics are optional. 579 Antibiotics should be used in cases of systemic illness; cellulitis; rapid pro- gression; d eeper or extensive infection;, hand, face, or genital involvement; and in patients with imm unosuppression, significant comorbid illness, septic phlebitis, and the elderly. If used, t he usual recommendation is TMP/SMX or doxycycline, clindamycin, or linezolid (much more exp ensive). For patients requiring hospitalization vancomycin, linezolid, and daptomycin (exce pt in lung) can be used. Ceftaroline and telavancin can be considered in skin and soft-tiss ue infections. Preventive measures: Isolate recently admitted patients with suspected MRSA. Group MRSA patients together or place in single isolation rooms. Cleanse hands (alcohol ge l is good) and use gloves and gowns in patient rooms. Use dedicated stethoscope or cleanse it after con- tact. Ask about the need for eradication (with mupirocin). Be meticulous in l ooking after intravascular catheters. Perform surveillance swabs of patients and possibly s taff during outbreaks. Masks may be needed during contact with MRSA pneumonia. Management o f recurrent MRSA skin infection: Cover draining wounds to reduce spread; maintain good pers onal hygiene; cleanse towels, linens, and clothes that have come in contact with MRSA wound ; trim long fingernails because under surfaces may be sites of colonization. Cleanse high-t ouch surfaces in the home. Consider personal decolonization with mupirocin twice daily to a nterior nares for 5 \200\22310 d and skin antiseptic (e.g., chlorhexidine) for 5 \200\22314 d. Streptococci Group A streptococci (e.g., S. pyogenes ) are common pathogens, causing wo und and skin infections (e.g., impetigo, erysipelas), tonsillitis, scarlet fever, necrotizi ng fasciitis, toxic shock, or septicemia. Late complications are rheumatic fever and postst reptococcal glomerulo- nephritis. S. pneumoniae ( Pneumococcus, gram-positive diplococcus) causes pneumonia, otitis media, meningitis, septicemia, and peritonitis (rare). Resistance to penicillin is a problem. S. sanguis, S. mutans , and S. mitis (of the \200\234viridans \200\235 group), S. bovis , and Enterococcus faecalis all cause SBE. E. faecalis also cause s UTI, wound infections, and septicemia. S. mutans is a very common cause of dental caries. S. milleri forms abscesses (e.g., in CNS, lungs, and liver). Most streptococci are sensiti ve to the penicillins, but E. faecalis and E. faecium may present some difficulties. They u sually respond to a combination of ampicillin and an aminoglycoside (e.g., gentamicin). Van comycin-resistant enterococci (VRE) are generally sensitive to linezolid and daptomycin, al though resistance is emerging. Anthrax ( Bacillus anthracis ): Occurs in Africa, Asia, Chin