Bacterial infections
Tuberculosis in HIV infection is treated in the standard way with isoniazid and rifampicin plus either pyrazinamide or ethambutol. Rifampicin is a potent enzyme inducer and increases the metabolism of drugs such as oral contraceptives, dapsone, fluconazole, ketoconazole and anticonvulsants.
Clinicians should also be aware of drug interactions between rifamycins (rifampicin and rifabutin) and antiretroviral drugs, particularly the protease inhibitors (Pls) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs). Certain combinations of each are contraindicated or require dose adjustment toBox 9.4 Treatment of MAC
Clarithromycin 1 g—2 g daily in divided doses +
Ethambutol 15mg∕kg∕day daily
+
Either Rifabutin 450-600mg daily Rifampicin 450-600mg daily Ciprofloxacin 500mg twice daily Clofazimine 100mg daily
3 or 4 drug regimens are recommended maintain therapeutic levels. Knowledge of these potential interactions is essential to avoid loss of clinical efficacy or increased risk of drug toxicity.
Although extrapulmonary disease is more common in HIV seropositive patients than in uninfected controls, the responses to treatment appear similar in the developed world if patients are compliant. Over the last few years there have been several outbreaks of tuberculosis with multiple drug-resistance (MDR) in the USA and Europe including the UK. Transmission of drug-resistant strains has occurred between patients and from patients to family members, healthcare workers and prison guards. Mortality from drug-resistant tuberculosis in this setting is high, around 70-90%. To reduce the risk of MDR TB it is essential to ensure adherence to antituberculosis therapy by patients and for healthcare facilities to have in place procedures and facilities to reduce the risk of nosocomial transmission.
Disseminated infection with Mycobacterium avium complex (MAC) causes considerable morbidity and mortality in the later stages of HIV infection (when CD4 counts are persistently below 50 ? 106∕l).
Various combinations of drugs have been shown to decrease mycobacteraemia and improve symptoms in uncontrolled studies. Four, three and two drug regimens have and are being assessed in clinical trials. A commonly used regimen in clinical practice is rifampicin or rifabutin (450-600 mg∕day), ethambutol (15 mg∕kg, max 1 g∕day) and clarithromycin (500mg twice a day). Other drugs that have been studied and may be considered include: clofazimine (100 mg∕day), ciprofloxacillin (500-75 mg twice a day), parental amikacin (7.5-15 mg daily for 2-4 weeks) and another macrolide azithromycin.Primary prophylaxis has been shown to significantly reduce the incidence of M.avium complex bacteriaemia and should be considered in patients whose CD4 counts are less than 75 ? 106∕l. A variety of agents have been shown to be effective including rifabutin 300mg daily, clarithromycin 500 mg twice daily or azithromycin 1200 mg once weekly. Resistant strains on clarithromycin and azithromycin prophylaxis can occur in those who develop breakthrough bacteriaemia, and there is crossresistance. A combination of once weekly azithromycin and once daily rifabutin is probably the most effective prophylaxis regimen and may also provide additional prophylaxis against PCP.
Salmonella infections are treated with either co-trimoxazole or ciprofloxacin and campylobacter with ciprofloxacin. In salmonella infections relapses of enteritis or bacteraemia are common.