Sikhamani Rajasekaran

Decreased Bioavailability of Rifampin and Other Antituberculosis Drugs in Patients with Advanced Human Immunodeficiency Virus Disease

ABSTRACT We evaluated the effects of human immunodeficiency virus (HIV) disease on pharmacokinetics of antituberculosis medications by measuring concentrations of isoniazid and rifampin in blood and of pyrazinamide and ethambutol in urine. Peak concentration and exposure were reduced for rifampin, and rapid acetylators of isoniazid had lower drug levels. HIV and HIV-tuberculosis patients who have diarrhea and cryptosporidial infection exhibit decreased bioavailability of antituberculosis drugs.

Malabsorption of Rifampin and Isoniazid in HIV-Infected Patients With and Without Tuberculosis

The absorption of rifampin, isoniazid, and D-xylose in patients with human immunodeficiency virus (HIV) infection and diarrhea, in patients with HIV infection and tuberculosis (TB), in patients with pulmonary TB alone, and in healthy subjects was studied. Percentage of dose of the drugs, their metabolites, and D-xylose excreted in urine were calculated. A significant reduction in the absorption of drugs and D-xylose in both the HIV infection/diarrhea and HIV infection/TB groups was observed (P<.05), and the correlation between them was significant. Our results indicate that patients with HIV infection and diarrhea and those with HIV infection and TB have malabsorption of rifampin and isoniazid.

CYP2B6 G516T Polymorphism but Not Rifampin Coadministration Influences Steady-State Pharmacokinetics of Efavirenz in Human Immunodeficiency Virus-Infected Patients in South India

ABSTRACT The dose of efavirenz during concomitant rifampin (RMP) administration is a matter of debate. We studied the influence of RMP coadministration on the steady-state pharmacokinetics of efavirenz in human immunodeficiency virus type 1 (HIV-1)-infected patients in South India. Fifty-seven HIV-tuberculosis (TB)-coinfected and 15 HIV-1-infected patients receiving combination antiretroviral therapy (CART) with an efavirenz (600 mg once daily)-containing regimen were recruited. HIV-TB-coinfected patients were receiving treatment with RMP-containing regimens. A complete pharmacokinetic study was conducted with 19 HIV-TB patients on two occasions (with and without RMP). Trough concentrations of efavirenz were measured in the remaining 38 patients during RMP coadministration. The 15 HIV-infected patients underwent complete pharmacokinetic sampling on one occasion. Plasma efavirenz was estimated by high-performance liquid chromatography, and genotyping of CYP2B6 G516T polymorphism was performed by sequencing. Peak and trough concentrations and exposure to efavirenz were significantly higher in TT than in GT and GG genotype patients (P < 0.001). Although RMP coadministration decreased the peak and trough concentrations and exposure to efavirenz by 17.8, 20.4, and 18.6%, respectively, the differences were not statistically significant. The trough concentration of efavirenz was subtherapeutic (less than 1.0 μg/ml) in 6 (8%) of 72 patients. In this South Indian population of HIV-infected patients, CYP2B6 G516T polymorphism but not RMP coadministration significantly influenced the pharmacokinetics of efavirenz; patients with the TT genotype had very high blood levels of efavirenz. While a small proportion of patients had subtherapeutic efavirenz levels, the clinical implications are uncertain, as all had good immunological responses to CART.

Association of high T allele frequency of CYP2B6 G516T polymorphism among ethnic south Indian HIV-infected patients with elevated plasma efavirenz and nevirapine

location and similar symptoms after 35 months of follow-up, but refused further diagnostic or therapeutic attempts. Another four patients experienced local infectious complications probably related to the former actinomycosis at 4, 25, 27 and 30 months after the end of treatment, respectively. Treatment duration in 5 of these 6 patients had a length of ,3 months and was significantly shorter than that of the 35 patients with an uneventful follow-up (P1⁄40.001, two-sided Mann–Whitney U-test). According to reviews, the recommended treatment length consists of several weeks of intravenous therapy followed by 6–12 months of oral treatment. Recently, the concept of shorter treatment courses has been introduced, especially for cervicofacial actinomycosis. Case series involving patients with pulmonary actinomycosis, treated exclusively medically with short course regimens, are sparse: a few series with a maximum number of 15 patients showed treatment successes after antibiotic regimens shortened to a median duration of 4–20 weeks; however, follow-up data were often missing or incomplete. – 6 In our series, 24 patients (56%) were treated for ,6 months without prior surgical debulking and with a clinical cure rate of 100%. On the other hand, 10 of 13 patients with evidence of abscess formation or chest wall involvement were treated for .6–14 months because of slow resolution of the radiographic lesions. Six of 41 patients (15%) with complete follow-up data developed either documented or possible recurrence or local complications. These patients received significantly shorter antibiotic courses when compared with the other patients, and duration was below 3 months in five of them. We suggest that antibiotic treatment duration should be individualized, and termination of treatment can probably be considered 1 or 2 months after complete clinical and radiological disease resolution in most patients. However, treatment durations below 3 months in medically treated patients without prior surgical debulking should probably be avoided, as they might be associated with an increased risk of complications. The main limitations of our study are those generally inherent in retrospective analyses. We were not able to calculate the diagnostic accuracy of the applied procedures in detail, and we cannot provide a prospective comparison between different antibiotics and treatment durations. However, due to the sporadic occurrence of actinomycosis, prospective trials might be nearly impossible to perform, and our case series represents the largest report on pulmonary actinomycosis in the recent literature. We conclude that (i) surgical diagnostic procedures can be avoided in the majority of patients by performing transbronchial catheter biopsies and/or transthoracic needle aspiration, (ii) antibiotic treatment with penicillin and alternatively doxycycline is associated with an excellent clinical cure rate despite high rates of penicillin intolerance, and (iii) individual treatment duration can be shortened below the recommended 6–12 months; however, treatment below 3 months in exclusively medically treated patients might be associated with complications during follow-up.

Actividad esterasa en especies de Candida procedentes de pacientes inmunodeficientes

A total of 149 clinical isolates of Candida species isolated from immunocompromised patients were examined to ascertain their esterase activity by the Tween 80 opacity test, which is a biochemical test used mainly to differentiate between Candida albicans and Candida dubliniensis. Our results showed that C. albicans (92.3%), Candida tropicalis (92.3%), Candida parapsilosis (25%), C. dubliniensis (16.6%), Candida inconspicua (100%), and Candida lipolytica (100%) produced opacity halos through the 10-day post-inoculation period. The remaining Candida species did not produce a positive test response. These findings indicate that Tween 80 opacity test cannot be used as the sole phenotypic trait in the differentiation of C. albicans and C. dubliniensis.

Carriage of Candida species in oral cavities of HIV infected patients in South India.

Fifty‐four patients with human immunodeficiency virus (HIV) infection were studied to assess the load of oral carriage of Candida spp. The mean oral Candida carriage density (30 305.93 ± 56 643.93 CFU ml−1) in HIV patients was significantly higher than that seen in the control population (93.48 ± 358.48 CFU ml−1; P = 0.000). The mean Candida load in HIV patients with oral thrush (46 591.43 ± 65 002.57 CFU ml−1) was significantly higher than in the HIV subjects without oral thrush (306.32 ± 699.50 CFU ml−1; P = 0.000). Non‐C. albicans Candida species (56%) were more predominant than the C. albicans (44%) isolates. 25S rDNA PCR analysis of C. albicans revealed preponderance of genotype A strains. Interestingly, 42.6% of rinse specimens grew multiple Candida species, with the combination of C. albicans and C. krusei (39.1%) being the most frequent.

Immune reconstitution syndrome in a child with TB and HIV

Immune reconstitution syndrome (IRS) is the transient worsening or appearance of new signs, symptoms, or radiological manifestation of an opportunistic infection occurring after the initiation of Highly active antiretroviral therapy (HAART) and is not due to treatment failure or new infection. We describe a case of a HIV infected child with tubercular (mediastinal) lymphadenitis with worsening of clinical and radiological features on starting HAART.

Evaluation of a diagnostic algorithm for sputum smear-negative pulmonary tuberculosis in HIV-infected adults.

Background:The Revised National TB Control Program bases diagnosis of tuberculosis (TB) on sputum smear examination and response to a course of antibiotics, whereas World Health Organization recommends early chest radiography [chest x-ray (CXR)] for HIV-infected symptomatic patients. We evaluated the utility of initial CXR in the diagnostic algorithm for symptomatic HIV-infected patients with negative sputum smears. Methods:HIV-infected ambulatory patients with cough or fever of ≥2 weeks and 3 sputum smears negative for acid-fast bacilli were enrolled in Chennai and Pune, India, between 2007 and 2009. After a CXR and 2 sputum cultures, a course of broad-spectrum antibiotics was given and patients were reviewed after 14 days. Sensitivity, specificity, positive and negative predictive values of symptoms, CXR, and various combinations for diagnosing pulmonary tuberculosis (PTB) were determined, using sputum culture as gold standard. Results:Five hundred four patients (330 males; mean age: 35 years; median CD4: 175 cells per cubic millimeter) were enrolled. CXR had a sensitivity and specificity of 72% and 57%, respectively, with positive predictive value (PPV) of 21% and negative predictive value (NPV) of 93% to diagnose PTB. TB culture was positive in 49 of 235 patients (21%) with an abnormal initial CXR and 19 of 269 patients (7%) with a normal CXR (P < 0.001). Sensitivity and specificity of cough ≥2 weeks for predicting PTB was 97% and 6%, with PPV and NPV of 14% and 94%, respectively. Conclusions:Although moderately sensitive, basing a diagnosis of TB on initial CXR leads to overdiagnosis. An absence of weight loss had a high NPV, whereas none of the combinations had a good PPV. A rapid and accurate diagnostic test is required for HIV-infected chest symptomatic.

Extended-spectrum β-lactamase/AmpC-producing uropathogenic Escherichia coli from HIV patients: do they have a low virulence score?

Extended-spectrum β-lactamase (ESBL) production and quinolone resistance are often associated in enterobacteria. Prior exposure to 3G cephalosporins/quinolones accelerates the risk of resistance to both these groups of antibiotics. Hence, information on the antimicrobial resistance pattern of uropathogenic Escherichia coli (UPEC) isolates is important to better formulate the guidelines for the empirical therapy of urinary tract infection in the context of HIV/AIDS. The aim of this study was to determine the incidence of ESBL/AmpC and fluoroquinolone (FQ) resistance among urinary E. coli isolates and to establish the association of extraintestinal virulence and phylogenetic distribution with antibiotic resistance and host immunocompromisation. Accordingly, 118 urinary Escherichia coli isolates from HIV (n = 76) and non-HIV antenatal patients (n = 42) from Chennai, South India, were analysed for the presence of five virulence-associated genes (VAGs): pap, sfa/foc, afa/dra, iutA and kpsMII. Compared with the susceptible HIV isolates, the majority of the ESBL(+)AmpC(+)FQ(R) isolates harboured iutA (66.7%) and pap (40%). The FQ-resistant HIV isolates were significantly enriched for iutA (67.8%) and kpsMII (47.5%) and qualified as UPEC (54.2%), while a majority of the FQ-susceptible isolates from the non-HIV patients were found to harbour pap (48.4%), sfa/foc (41.9%) and kpsMII (48.4%) and were classified as UPEC (40.5%). We conclude that antibiotic-resistant (ESBL(+)AmpC(+)and/or FQ(R)) phylogroup D isolates with limited virulence are competent enough to establish infections in HIV patients, while among non-HIV patients, an array of virulence factors is essential for E. coli to overcome host defences irrespective of antibiotic resistance.

Fluoroquinolone resistance among CTX-M producing uropathogenic Escherichia coli from HIV and non-HIV patients in South India

Background Extended spectrum b-lactamase (ESBL) especially, the CTX-M producing Escherichia coli has emerged world wide as the leading cause of community onset UTI in the era of antibiotic resistance. The CTX-M producers often exhibit co-resistance towards fluoroquinolones and are a growing challenge to patient care. The purpose of this study was to determine the incidence of fluoroquinolone resistance among CTX-M producing uropathogenic E.coli (UPEC).