Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents Disease Specific Recommendations Bacterial Enteric Disease Epidemiology        The three most common causes of bacterial diarrhea among patients with HIV-1 infection in developed countries are Salmonella, Campylobacter, and Shigella species. Patients with HIV-1 infection are at increased risk for developing salmonellosis. Two studies in the United States and Europe reported incidence rates 20--100-fold higher than the incidence in the general population without HIV-1 infection (289--292). As with non-HIV--associated salmonellosis, the probable source for Salmonella infection is ingestion of contaminated food, in particular undercooked poultry and eggs (290). Acquisition of the infection might be facilitated by HIV-1--associated gastric achlorhydria. Campylobacter jejuni has a reported incidence among HIV-1--infected persons, particularly men who have sex with men (MSM), up to 39 times higher than in the general population (293,294). Persons with HIV-1 infection, particularly sexually active MSM, appear to be at increased risk for developing shigellosis. A population-based surveillance study conducted in 1996 found the following incidence ratios compared with the HIV-seronegative and heterosexual population: MSM and HIV-seronegative 4.9 (95% confidence interval [CI] = 2.7--8.1); heterosexual and HIV-1 infected 30.6 (95% CI = 12.8--63.0); and MSM and HIV-1 infected 35.7 (95% CI = 25.1--50.4) (295). Shigella bacteremia is more common among HIV-1--infected persons and might occur in both mild and severe cases of clinical shigellosis (296). Relapses in gastroenteritis and bacteremia after appropriate treatment have also been reported (296).   Clinical Manifestations The three major clinical syndromes of salmonellosis among patients with HIV-1 infection include a self-limited gastroenteritis; a more severe and prolonged diarrheal disease, associated with fever, bloody diarrhea, and weight loss; and Salmonella septicemia, which might present with or without gastrointestinal symptoms. Bacteremia can occur with each of these syndromes and is more likely to occur among those with advanced immunosuppression  In the United States, the majority of cases of Salmonella septicemia are caused by nontyphoidal strains, in particular S. enteritidis and S. typhimurium. Because nontyphoidal Salmonella bacteremia is rare in immunocompetent hosts, its diagnosis should prompt consideration of HIV testing. An additional important feature of Salmonella bacteremia among patients with AIDS is its propensity for relapse. On the basis of data from early in the AIDS epidemic, the rate of recurrent bacteremia was approximately 45% unless chronic suppressive therapy was administered . Campylobacter disease among those with severe or progressive immunodeficiency is often associated with more prolonged diarrhea, invasive disease, bacteremia, and extraintestinal involvement .    The development of antimicrobial resistance during therapy, often associated with clinical deterioration or relapse, is also reported more frequently among HIV-1--infected persons . Shigellosis among persons with HIV-1 infection generally causes an acute, febrile, diarrheal illness with prominent upper and lower gastrointestinal symptoms. Bloody diarrhea is more commonly observed with Shigella infection than with Salmonella infection .     Diagnosis The diagnosis of bacterial enteric infection is established through cultures of stool and blood. Because of the high rate of bacteremia associated with Salmonella gastroenteritis, in particular among patients with advanced HIV-1 disease, blood cultures should be obtained from any HIV-1--infected patient with diarrhea and fever. Persons with HIV-1 are also at risk for disease caused by nonjejuni Campylobacter species, including C. fetus, C. upsaliensis, C. laridis, C. cineadi, and C. fennelliae. Although blood culture systems will generally grow these organisms, routine stool cultures performed by most laboratories will fail to identify these more fastidious Campylobacter species. Endoscopy can be diagnostically useful. If lower endoscopy is performed, ulcerations similar to those seen with cytomegalovirus colitis might be evident and can only be distinguished through histopathologic examination and culture.   Treatment Recommendations Immunocompetent hosts without HIV-1 infection often do not require treatment for Salmonella gastroenteritis; the condition is self-limited and treatment might prolong the carrier state. Although no treatment trials have examined this strategy among patients with HIV-1 infection, the risk for bacteremia is sufficiently high that the majority of specialists recommend treatment of all HIV-1--associated Salmonella infections (BIII). The initial treatment of choice for Salmonella infection is a fluoroquinolone  (AIII). Ciprofloxacin is the preferred agent  (AIII); it is likely that other fluoroquinolones (levofloxacin, gatifloxacin and moxifloxacin) also would be effective in treatment of salmonellosis among HIV-1--infected persons, but these have not been well evaluated in clinical studies (BIII). The length of therapy for HIV-1--related Salmonella infection is poorly defined. For mild gastroenteritis without bacteremia, 7--14 days of treatment is reasonable in an effort to reduce the risk for extraintestinal spread (BIII). Among patients with advanced HIV-1 disease (CD4+ T lymphocyte count <200/mL) or who have Salmonella bacteremia, at least 4--6 weeks of treatment is often recommended (BIII). Depending on antibiotic susceptibility, alternatives to the fluoroquinolone antibiotics for Salmonella spp. include TMP-SMX or expanded spectrum cephalosporins (e.g., ceftriaxone or cefotaxime) (BIII). As with non-HIV--infected patients, the optimal treatment of campylobacteriosis among persons with HIV-1 infection is poorly defined. Among patients with mild disease, certain clinicians might opt to withhold therapy unless symptoms persist for more than several days. Increasing resistance to fluoroquinolones makes the choice of therapy especially problematic. For mild-to-moderate disease, initiating therapy with a fluoroquinolone (ciprofloxacin) or a macrolide (azithromycin), pending susceptibility test results, and treating for 7 days is a reasonable approach (BIII). Patients with bacteremia should be treated for at least 2 weeks (BIII), and adding a second active agent (e.g., an aminoglycoside) might be prudent (CIII). Therapy for shigellosis is indicated both to shorten the duration of illness and to prevent spread of the infection to others  (AIII). The recommended treatment is with a fluoroquinolone for 3--7 days (AIII). Alternatives to this treatment include TMP-SMX for 3--7 days or azithromycin for 5 days (BIII). Cases of Shigella acquired internationally have high rates of TMP-SMX resistance; in addition, HIV-1--infected persons have higher rates of adverse effects related to this agent. As a result, fluoroquinolones are preferred as first-line. Treatment of patients who have Shigella bacteremia is less well defined. Depending on the severity of infection, it might be reasonable to extend treatment to 14 days, using the agents described previously (AIII).   Monitoring and Adverse Events Patients should be monitored closely for response to treatment, as defined clinically by improvement in systemic signs and symptoms and resolution of diarrhea. A follow-up stool culture to demonstrate clearance of the organism is not generally required if a complete clinical response has been demonstrated but should be considered for those who fail to clinically respond to appropriate antimicrobial therapy, or when public health considerations dictate the need to ensure microbiologic cure (e.g., health-care or food service workers).   Management of Treatment Failure Treatment failure is defined by the lack of improvement in clinical signs and symptoms of diarrheal illness and the persistence of organisms in stool, blood, or other relevant body fluids or tissue after completion of appropriate antimicrobial therapy for the recommended duration. Certain patients with Salmonella bacteremia might remain febrile for 5--7 days despite effective therapy. Therefore, careful observation is required to determine the adequacy of the response. Treatment should be guided by drug susceptibility testing of isolates recovered in culture. An evaluation of other factors that might contribute to failure or relapse, such as malabsorption of oral antibiotics, a sequestered focus of infection (e.g., an undrained abscess), or adverse drug reactions that interfere with antimicrobial activity, should be undertaken as indicated.   Prevention of Recurrence HIV-1--infected persons who have Salmonella bacteremia should receive long-term secondary prophylaxis (chronic maintenance therapy) to prevent recurrence. Fluoroquinolones, primarily ciprofloxacin, are usually the drugs of choice for susceptible organisms (BII). Chronic suppressive or maintenance therapy is not generally recommended for Campylobacter or Shigella infections among persons with HIV-1 infection (EIII). Household contacts of HIV-1--infected persons who have salmonellosis or shigellosis should be evaluated for persistent asymptomatic carriage of Salmonella or Shigella so that strict hygienic measures or antimicrobial therapy can be instituted and recurrent transmission to the HIV-1--infected person can be prevented (CIII).   Special Considerations During Pregnancy The diagnosis of bacterial enteric infections among pregnant women is the same as among nonpregnant women. Bacterial enteric infections should be managed as in the nonpregnant adult, with several considerations. Because arthropathy has been observed among immature animals with the use of quinolones during pregnancy, quinolones are generally not recommended in pregnancy and among children aged <18 years. Therefore, expanded spectrum cephalosporins, TMP-SMX or azithromycin, depending on the organism and the results of susceptibility testing, should generally be considered as first-line therapy (CIII). However, >200 cases of ciprofloxacin use in pregnancy have been reported to various pregnancy registries, and its use has not been associated with arthropathy or birth defects after in utero exposure in humans. Therefore, quinolones can be used in pregnancy for drug-resistant disease (CIII). Neonatal-care providers should be informed of maternal sulfa therapy if used near delivery because of the theoretical increased risk to the newborn of hyperbilirubinemia and kernicterus.