Thambu David Sudarsanam

Risk factors for MDR and XDR-TB in a tertiary referral hospital in India.

Background India has a high burden of drug resistant TB, although there are few data on XDR-TB. Although XDR-TB has existed previously in India, the definition has not been widely applied, and surveillance using second line drug susceptibility testing has not been performed. Our objective was to analyze clinical and demographic risk factors associated with isolation of MDR and XDR TB as compared to susceptible controls, at a tertiary center. Methodology/Findings Retrospective chart review based on positive cultures isolated in a high volume mycobacteriology laboratory between 2002 and 2007. 47 XDR, 30 MDR and 117 susceptible controls were examined. Drug resistant cases were less likely to be extrapulmonary, and had received more previous treatment regimens. Significant risk factors for XDR-TB included residence outside the local state (OR 7.43, 3.07-18.0) and care costs subsidized (OR 0.23, 0.097-0.54) in bivariate analysis and previous use of a fluoroquinolone and injectable agent (other than streptomycin) (OR 7.00, 95% C.I. 1.14-43.03) and an initial treatment regimen which did not follow national guidelines (OR 5.68, 1.24-25.96) in multivariate analysis. Cavitation and HIV did not influence drug resistance. Conclusions/Significance There is significant selection bias in the sample available. Selection pressure from previous treatment and an inadequate initial regimen increases risk of drug resistance. Local patients and those requiring financial subsidies may be at lower risk of XDR-TB.

One year trends in the gram-negative bacterial antibiotic susceptibility patterns in a medical intensive care unit in South India

PURPOSE To describe the changes in antibiotic susceptibility patterns of common intensive care unit pathogens with time from the medical intensive care unit of a tertiary care hospital. METHODS A prospective observational study was conducted in the medical intensive care unit (MICU) of a 2100 bed tertiary care hospital in South India. All data regarding patient characteristics, disease characteristics, infective agents, identified along with their antibiotic sensitivity patterns and patient outcomes were prospectively recorded in MICU data base. Various bacterial pathogen antibiotic sensitivity patterns from August 2004 to May 2005 were prospectively documented. During this period 491 patients were admitted to the MICU. Data were analyzed using excel spreadsheets. RESULTS Ceftazidime resistance reduced in Klebsiella spp. while cefotaxime resistance increased. In E. coli however, ceftazidime and cefotaxime resistance increased. Klebsiella resistance to cefotaxime and ceftazidime ranged from 25-50% and 14-91%, while E. coli resistance to these antibiotics ranged from 50-70% and 50 to 80% respectively. In Pseudomonas and the non-fermenting gram-negative bacteria (NFGNB) ceftazidime resistance decreased. Third generation cephalosporin resistance seemed to be reducing in the NFGNB, however, carbapenem resistance appeared to be increasing, possibly due to their increasing use. CONCLUSIONS This study demonstrates the trend in antibiotic susceptibility pattern (AST) of common gram negative infections seen in intensive care units. It demonstrates the changes seen especially after a change in the protocol antibiotic. Changes in the AST patterns of Klebsiella, E. coli, Pseudomonas and non-fermenting gram negative bacteria were seen. The data on the changing antibiotic susceptibility trends we believe is an important pillar in our efforts at infection control especially in intensive care settings.

Leflunomide: a possible alternative for gangciclovir sensitive and resistant cytomegalovirus infections

The search for newer more cost effective treatments for infectious diseases remains a challenge. Cytomegalovirus (CMV) infection, which is especially common in the immunosupressed, is an important challenge for treating physicians. Gangciclovir’s cost is a major hurdle in developing countries. Leflunomide is cheaper and is easily given orally. It works by a novel mechanism inhibiting virion assembly. It also has immunosuppressive properties. It and has been shown to be effective in both gangciclovir sensitive as well as resistant cases of CMV infection. Given these considerations we believe that leflunomide is an exiting new drug for CMV infection. However, hepatotoxicity and teratogenicity are known side effects. The exact dose and duration of treatment for CMV infection, for secondary prophylaxis, and in situations of gangciclovir resistance need further study.

Predictors of mortality in mechanically ventilated patients

Objectives: There are scarce data from India validating scoring systems used to predict outcome in patients requiring mechanical ventilation. This study prospectively compared the organ system failure (OSF), the acute physiology and chronic health evaluation (APACHE) II, and the APACHE III, scores on patients requiring mechanical ventilation in the medical intensive care unit, to predict outcome. Methods: 200 consecutive patients requiring mechanical ventilation in a medical intensive care unit were recruited. OSF, APACHE II, and APCHE III scores were calculated at admission and daily for one week or until discharge in all patients. Other variables recorded include age, sex, diagnosis, oxygen therapy before ventilation, complications on ventilation, duration in hospital before ventilation, duration of ventilation, type of respiratory failure, alveolar arterial oxygen gradient, P/F ratio, use of tracheostomy, time on ventilator before tracheostomy, muscle relaxant used, fluid balance, inotrope support. Logistic regression analysis and area under the curve were computed to determine which variables independently predict outcome. Results: Of the 200 patients, at discharge 143 patients (71.5%) had died. The factors that independently predicted outcome among these patients on mechanical ventilation were the type of respiratory failure (type I) OR = 2.7 (p = 0.02), the use of inotropes OR 2.4 (p = 0.04), and the APACHE II score OR = 1.8 (p = 0.008) for every five point increase in APACHE II score. Conclusions: Type 1 respiratory failure, the use of inotropes, and the APACHE II score measured at admission are significant independent predictors of mortality in the patients on mechanical ventilation.

Evidence for lower CD4+ T cell and higher viral load in asymptomatic HIV-1 infected individuals of India: Implications for therapy initiation

PURPOSE We have earlier documented that the south Indian population had lower CD4 counts. The aim of this study was to investigate a previous suggestion on a new CD4+ T cell cut off and association with HIV-1 RNA levels for decision on anti retroviral therapy in India (south). METHODS We evaluated a new methodology i.e., artus real-time PCR and CD4+ T cell count by Guava EasyCD4 system. From 146 HIV infected individuals seen at a tertiary care centre, blood was collected for CD4+ T cell and HIV-1 RNA estimation. RESULTS The receiver operating characteristic curve cut off value for the CD4 counts to distinguish between CDC clinical categories A and B was 243 cells/microL, and to distinguish B and C was 153 cells/microL. The RNA level that differentiated CDC A and B was 327473 RNA copies/mL, while for CDC B and C was 688543 copies/mL. There was a significant negative correlation (r = -0.55, P + T cell counts in HIV infected individuals. CONCLUSIONS A majority with CD4 counts of 201-350 cells/microL in our population had higher viral load than the treatment threshold suggested by the International AIDS society and the above two methodologies are useful in monitoring HIV infections.

Acute undifferentiated febrile illness in patients presenting to a Tertiary Care Hospital in South India: clinical spectrum and outcome

Background: Acute undifferentiated febrile illness (AUFI) may have similar clinical presentation, and the etiology is varied and region specific. Materials and Methods: This prospective observational study was conducted in a tertiary hospital in South India. All adult patients presenting with AUFI of 3-14 days duration were evaluated for etiology, and the differences in presentation and outcome were analyzed. Results: The study cohort included 1258 patients. A microbiological cause was identified in 82.5% of our patients. Scrub typhus was the most common cause of AUFI (35.9%) followed by dengue (30.6%), malaria (10.4%), enteric fever (3.7%), and leptospirosis (0.6%). Both scrub typhus and dengue fever peaked during the monsoon season and the cooler months, whereas no seasonality was observed with enteric fever and malaria. The mean time to presentation was longer in enteric fever (9.9 [4.7] days) and scrub typhus (8.2 [3.2] days). Bleeding manifestations were seen in 7.7% of patients, mostly associated with dengue (14%), scrub typhus (4.2%), and malaria (4.6%). The requirement of supplemental oxygen, invasive ventilation, and inotropes was higher in scrub typhus, leptospirosis, and malaria. The overall mortality rate was 3.3% and was highest with scrub typhus (4.6%) followed by dengue fever (2.3%). Significant clinical predictors of scrub typhus were breathlessness (odds ratio [OR]: 4.96; 95% confidence interval [CI]: 3.38-7.3), total whole blood cell count >10,000 cells/mm 3 (OR: 2.31; 95% CI: 1.64-3.24), serum albumin <3.5 g % (OR: 2.32; 95% CI: 1.68-3.2). Overt bleeding manifestations (OR: 2.98; 95% CI: 1.84-4.84), and a platelet count of <150,000 cells/mm 3 (OR: 2.09; 95% CI: 1.47-2.98) were independent predictors of dengue fever. Conclusion: The similarity in clinical presentation and diversity of etiological agents demonstrates the complexity of diagnosis and treatment of AUFI in South India. The etiological profile will be of use in the development of rational guidelines for control and treatment of AUFI.

Genotypic resistance profile of HIV-1 protease gene: A preliminary report from Vellore, south India

HIV-1 subtypes other than B are responsible for most new HIV infections worldwide; virus sequence data for drug resistance is described only from a limited number of non-B subtype HIV-1. This study is on mutations and polymorphisms of HIV-1 protease gene that can predict drug resistance in subtype C. The genotypic resistance assay was carried out on 38 HIV-1 strains with their plasma RNA and in nine, the proviral protease gene was sequenced. The treatment naïve strains showed minor resistance mutations, there were no major resistance mutations in the protease gene. We suggest the use of resistance testing to monitor individuals on therapy and also before initiation of therapy, gathering more sequence information for a data bank of Indian strains.

Acute abdomen: an unusual presentation of disseminated Penicillium marneffei infection.

Varied clinical presentations of Penicillium marneffei, an opportunistic pathogen in HIV disease has been rarely described in literature. We report a patient with advanced AIDS who presented to us with prolonged fever and had features of an acute abdomen. On radiologic imaging he had features of intestinal obstruction and mesenteric lymphadenitis. A diagnosis was made possible by endoscopic biopsies of the small bowel and bone marrow culture which grew P. Marneffei. He was treated with intravenous amphotericin for 2 weeks followed by oral itraconazole. This case is reported for its rarity and unusual presentation and to sensitise clinicians and microbiologists to consider this as an aetiology in patients with advanced HIV/AIDS who present with acute abdomen, more so in patients from a distinct geographic region--South-East Asia.

Postmortem trucut transnasal brain biopsy in the diagnosis of encephalitis

Diagnosing encephalitis is often difficult with a definitive diagnosis being reached at best in only 40% of cases. This clinical condition is associated with a high morbidity and mortality. A brain biopsy is the gold standard for the diagnosis of this disease. However, this procedure is rarely done, resulting in the cause of death being largely speculative. We propose a simple procedure for postmortem brain biopsy through the transnasal transcribriform route that will possibly be more acceptable to clinicians and relatives alike due to lack of external disfigurement, relative ease of the procedure and economy of time and manpower. This could also prove to be of immense benefit in an epidemic of encephalitis, especially in remote areas.

COST OF INTENSIVE CARE IN INDIA.

OBJECTIVES The majority of patients in India access private sector providers for curative medical services. However, there is scanty information on the cost of treatment of critically ill patients in this setting. The study evaluates the cost and extent of financial subsidy required for patients admitted to an intensive care unit (ICU) in India. METHODS Data on direct medical, direct nonmedical, and indirect cost were prospectively collected from critically ill patients admitted to a tertiary teaching hospital in India. Willingness-to-pay (WTP) amount was obtained from the next-of-kin following admission and the actual cost paid by the family at discharge was recorded. RESULTS The main diagnoses (n = 499) were infection (26 percent) and poisoning (21 percent). The mean APACHE-II score was 13.9 (95 percent confidence interval [CI], 13.3-14.5); 86 percent were ventilated. ICU stay was 7.8 days (95 percent CI, 7.3-8.3). Hospital mortality was 27.9 percent. Direct medical cost accounted for 77 percent (US