We investigated the population pharmacokinetics and pharmacogenetics of efavirenz in 307 patients coinfected with human immunodeficiency virus and tuberculosis and included in the Cambodian Early vs Late Initiation of Antiretrovirals trial (CAMELIA) in Cambodia. Efavirenz (600 mg/d) and stavudine plus lamivudine were administered in addition to standard antituberculosis treatment, including rifampicin and isoniazid. Blood samples were obtained a mean of 14 hours after efavirenz intake at weeks 2 and 6 after initiation of efavirenz and weeks 22 (efavirenz plus antituberculosis drugs) and 50 (efavirenz alone) after initiation of antituberculosis treatment. Ten patients participated in an extensive pharmacokinetic study after week 50. CYP2B6 G516T and C485-18T polymorphisms were the most significant covariates, with weight showing a significant minor effect. Change in efavirenz apparent clearance in patients taking both efavirenz and antituberculosis treatment was highly dependent on NAT2 polymorphism, as a possible surrogate of isoniazid exposure. Patients carrying the CYP2B6 516 TT genotype and slow-acetylation NAT2 phenotype had the lowest efavirenz apparent clearance. These data suggest that the inducing effect of rifampicin is counterbalanced by a concentration-dependant inhibitory effect of isoniazid on efavirenz clearance.

In South-east Asia, acid-fast bacillus smear-negative pneumonia is caused by a wide variety of pathogens. When possible, fiberoptic bronchoscopy must be performed rapidly if clinical data are not highly suggestive of bacterial pneumonia, Pneumocystis jiroveci pneumonia or tuberculosis. In contrast, in Africa, bacterial pneumonia and tuberculosis are responsible for the large majority of cases. Fiberoptic bronchoscopy should be restricted to patients with clinical and/or radiological findings not suggestive of bacterial pneumonia or tuberculosis, antibiotic failure, and three consecutive negative sputum smears.

The PCP score could provide a useful clinical tool to identify PCP among acid-fast bacillus smear-negative pneumonia and start specific therapy.

Melioidosis has never been officially reported from Cambodia. Here we report two cases, a 58-year-old male (case 1) and a 49-year-old female (case 2) who presented with respiratory illnesses featuring multiple lung abscesses. The sputum culture of both patients, taken in the framework of a laboratory-based study on aetiologies of (sub-)acute respiratory infections among hospitalized patients in southern Cambodia, grew Burkholderia pseudomallei. The most striking aspect of these case stories was the extent of the delays in diagnosis. Presenting with a 1-month history of respiratory symptoms, case 1 was first suspected of tuberculosis (TB) infection, and then misdiagnosed as 'metastatic lung cancer' in Phnom Penh, Cambodia. Case 2 suffered from pulmonary infections for >10 years, during which time she was treated for TB four times. Neither patient ever produced acid-fast-bacilli (AFB)-positive sputum. Following our laboratory confirmation, the patients were traced for re-admission. Under the 'classical' trimethoprim sulphamethoxazole, chloramphenicol and doxycycline treatment, their clinical status improved considerably within 2 weeks. The two study cases illustrate issues relating to the misdiagnosis of melioidosis in Cambodia; an unfamiliarity of clinicians with the disease, which is associated with a high prevalence of TB. Therefore, a heightened awareness of melioidosis among clinicians would have a substantial impact on public health as the non-septicaemic form of the disease is potentially treatable with antibiotics that are available in Cambodian public hospitals.

No abstract