Multidrug resistance mediated by co‑carriage of extended‑spectrum beta‑lactamases, AmpC and New Delhi metallo‑beta‑lactamase‑1 genes among carbapenem‑resistant Enterobacteriaceae at five Indian medical centres.

In this study, we evaluated the coexistence of extended‑spectrum beta‑lactamases (ESBL), AmpC and New Delhi metallo‑beta‑lactamase‑1 (NDM‑1) genes among carbapenem‑resistant Enterobacteriaceae (CRE) recovered prospectively from patients at multiple sites. The study included 285 CRE strains from 2782 Gram‑negative Bacilli collected from multiple centres during 2007–2010, of which 87 were characterised. Standard and reference laboratory methods were used for resistance determination. Detection of blaNDM‑1, blaAmpC, blaTEM, blaSHV and blaCTX‑M was done by polymerase chain reaction. High levels of antimicrobial resistance observed among study isolates. Co‑carriage of ESBLs, AmpC and NDM‑1 was 26.3%. Nosocomial origin among the co‑carriage isolates was 64.3%, with 9.2% associated mortality.

Assessing effect of climate on the incidence of dengue in Tamil Nadu.

Incidence of dengue is reported to be influenced by climatic factors. The objective of this study is to assess the association of local climate with dengue incidence, in two geographically distinct districts in Tamil Nadu. The study uses climate data, rainfall and mean maximum and minimum temperature to assess its association if any, with dengue incidence in two districts of Tamil Nadu, South India. According to this study while precipitation levels have an effect on dengue incidence in Tamil Nadu, non-climatic factors such as presence of breeding sites, vector control and surveillance are important issues that need to be addressed.

"The Chennai declaration" Recommendations of "A roadmap- to tackle the challenge of antimicrobial resistance" - A join meeting of medical societies of India.

"A Roadmap to Tackle the Challenge of Antimicrobial Resistance - A Joint meeting of Medical Societies in India" was organized as a pre-conference symposium of the 2 nd annual conference of the Clinical Infectious Disease Society (CIDSCON 2012) at Chennai on 24 th August. This was the first ever meeting of medical societies in India on issue of tackling resistance, with a plan to formulate a road map to tackle the global challenge of antimicrobial resistance from the Indian perspective. We had representatives from most medical societies in India, eminent policy makers from both central and state governments, representatives of World Health Organization, National Accreditation Board of Hospitals, Medical Council of India, Drug Controller General of India, and Indian Council of Medical Research along with well-known dignitaries in the Indian medical field. The meeting was attended by a large gathering of health care professionals. The meeting consisted of plenary and interactive discussion sessions designed to seek experience and views from a large range of health care professionals and included six international experts who shared action plans in their respective regions. The intention was to gain a broad consensus and range of opinions to guide formation of the road map. The ethos of the meeting was very much not to look back but rather to look forward and make joint efforts to tackle the menace of antibiotic resistance. The Chennai Declaration will be submitted to all stake holders.

Correlation of TEM, SHV and CTX-M extended-spectrum beta lactamases among Enterobacteriaceae with their in vitro antimicrobial susceptibility.

Purpose: The present study was carried out to characterize the ESBL types and evaluated their in vitro activity against a collection of Gram negative bacteria (GNB) from a multicentric Indian surveillance study. Material and Methods: During January 2005 to June 2006, six tertiary care centres in India forwarded 778 non-duplicate GNB to our reference laboratory. Three hundred GNB from this collection were selected based on clinical significance and were used in the present study. Tested isolates included Escherichia coli (167), Klebsiella spp. (122) and Enterobacter spp. (11). ESBL screening and confirmation was performed for all the isolates. Minimum inhibitory concentration of imipenem, meropenem, ertapenem, levofloxacin, amikacin, piperacillin/tazobactam and ceftriaxone was determined by the E-test method. Molecular typing of the ESBLs was performed by polymerase chain reaction among the 121 selected isolates. Results: The study showed excellent susceptibility among the strains to imipenem (100%), meropenem (100%) and ertapenem (98.7%); good susceptibility to amikacin (89.7%) and piperacillin/tazobactam (85.3%) was observed. TEM and CTX-M were predominantly found in E. coli (39.2%) while, among the Klebsiella spp., TEM, SHV and CTX-M occurred together in 42.6% of the isolates. Conclusion: More than one ESBL was produced by many strains, and this was correlated with increased resistance levels. Carbapenems continue to show good in vitro activity and ertapenem is a potential alternative to imipenem and meropenem. Continued antimicrobial resistance surveillance is warranted in light of these findings.

Detection and characterization of metallo beta lactamases producing Pseudomonas aeruginosa.

This study was undertaken to evaluate phenotypic and genotypic methods for detection of Metallo-Beta-Lactamases (MBLs) among nosocomial Pseudomonas aeruginosa. Sixty one among 176 P. aeruginosa isolates, collected as part of a multicentric study (2005-2007), were evaluated for carbapenem resistance (CARB-R; resistant to either imipenem/meropenem) and screened for MBL by Combination Disk Diffusion Test (CDDT) using imipenem (IMP), meropenem (MER) and ceftazidime (CAZ) with EDTA. MBL positives were further confirmed by IMP + EDTA Etest. Twenty strains (42.6%) were found to be MBL producers among the 61 P. aeruginosa. PCR for IMP and VIM MBL was performed on 48 of the 61, 15 were positive for VIM MBL type. CDDT using IMP + EDTA had the highest sensitivity and specificity of 87.8% and 84.4% when compared to Etest, which was higher than the values obtained for CAZ + EDTA and MER + EDTA. CDDT using IMP + EDTA also compared very well with the PCR (specificity = 90.9%, sensitivity = 93.3%). CARB-R among P. aeruginosa is mediated predominantly via MBL production. Clinical P. aeruginosa isolates can be screened routinely using the less expensive IMP + EDTA CDDT in clinical microbiology laboratories.

Granulomatous hepatitis following open heart surgery with cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) initiates an inflammatory cascade, predisposing the patient to a number of infections. The stress of surgery and anaesthesia further expose the patient to a variety of non-infectious complications. We report a group of patients who developed granulomatous disease after open heart surgery. METHODS: We retrospectively analysed a subset of patients who developed a syndrome of fever, jaundice and hepatomegaly after open heart surgery. We recruited age- and sex-matched controls who underwent open heart surgery during the same period (July 2002-July 2004). Details of demographic profiles, diagnostic evaluation and drug treatment were noted and compared between the two groups using the SPSS software. RESULTS: Five patients were identified to have the specific syndrome of high grade intermittent fever with jaundice and hepatomegaly with investigations revealing an intrahepatic cholestasis. A detailed evaluation revealed granulomas in tissue specimens of the bone marrow and/or liver in these patients. An extensive evaluation for an alternative aetiological agent was non-contributory. CONCLUSION: We found granulomatous hepatitis in 5 patients following open heart surgery and they were given conventional antituberculous therapy to which they responded. It is possible that in these patients, tuberculosis was re-activated from a dormant focus due to a period of transient immunodeficiency caused by an extracorporeal circulation.

Subtype & cytokine profiles of HIV infected individuals from south India.

BACKGROUND & OBJECTIVE: The global surveillance of human immunodeficiency virus (HIV) subtypes (clades) helps understand the global distribution and incidence of different HIV subtypes. As knowledge about subtypes circulating in an area is needed for developing a candidate vaccine, prevalence of the subtypes HIV-1 and HIV-2 were studied in south India. The profile of cytokines interleukin 10 (IL10) and interferon gamma (IFNgamma) in both types of infection were also analysed as these are considered indicators of disease progression. METHODS: Patients who belonged to the 4 south Indian States i.e. Tamil Nadu, Kerala, Karnataka and Andhra Pradesh were included. HIV-1 subtyping was carried out by the heteroduplex mobility analysis (HMA) while that of HIV-2 was done by direct sequencing. The quantitation of IFNgamma and IL-10 was carried out using commercial ELISA kits. RESULTS: Among the 82 HIV-1 infected individuals subtyped, 78 (95.1%) were subtype C while all 12 HIV-2 strains were subtype A. IL-10 concentration was significantly higher among HIV infected individuals compared to normal healthy controls. IFNgamma was significantly higher among symptomatic and AIDS groups compared to asymptomatic HIV-1 infected individuals. INTERPRETATION & CONCLUSION: HIV-1 subtype C and the HIV-2 subtype A are the major subtypes circulating in south India. The study showed a trend towards a shifting of the cytokine profile from Th1 to Th2/Th0 in HIV-1, HIV-2 infections, and HIV-1 and HIV-2 dual infected individuals as the disease progresses. This trend observed is not unlike that reported from the West, despite the difference in subtype profile.

Disseminated histoplasmosis.

OBJECTIVE: To study the clinical features and natural history of disseminated histoplasmosis(DH) in India. METHODS: We retrospectively analyzed the data obtained from the in-patient medical records of adults (age > 13 years) diagnosed to have DH during the period from January 1989 to December 1999. DH was diagnosed when histologically compatible intracellular organisms were present or Histoplasma capsulatum was obtained in culture from the extrapulmonary sites. RESULTS: Nineteen patients (18 male and 1 female) were diagnosed to have DH. Diabetes mellitus and HIV infection were the most common co-morbid conditions. Weight loss, fever and oropharyngeal ulcers were the commonest symptoms. Physical signs included hepatosplenomegaly, oropharyngeal ulcers and lymphadenopathy. The diagnosis was confirmed by histopathology and/or culture from the following sites: bone marrow, adrenal gland, lymph node, oropharyngeal ulcers, rectal mucosa and skin. Two patients were treated with Amphotericin B, 6 with various azoles and 3 had Amphotericin B followed by various azoles. Among the eleven treated, 7 were cured, 2 improved, 1 had a relapse and 1 patient died. CONCLUSION: DH is not uncommon in India and should be considered in the diagnosis of patients with prolonged fever, weight loss, oropharyngeal ulcers, hepatosplenomegaly, lymphadenopathy and adrenal enlargement. Correct diagnosis and treatment leads to a favourable outcome.

Clinical manifestations and management of cryptococcal infection.

Cryptococcus neoformans is an important fungal pathogen causing invasive infection, especially of the central nervous system in this era of the HIV/AIDS epidemic. The choice of treatment depends on site(s) of infection and the patient's immune status. Use of appropriate antifungal agents decreases mortality significantly, but requires continued therapy and long-term maintenance to prevent relapses. The use of liposomal amphotericin B (L Amp B) has overcome some of the difficulties usually found in this setting. The major advantage of these liposomal formulations are faster clearance of C. neoformans [cerebrospinal fluid (CSF) negative] and a reduction in amphotericin toxicity. The majority of clinical efficacy data related to L Amp B are derived from compassionate use studies and case series. Use of liposomal amphotericin has also shown to be a cost effective approach.

Pacemaker endocarditis caused by Pseudomonas aeruginosa treated successfully.

Infective endocarditis (IE) is a rare but serious complication of permanent cardiac pacemaker placement. Endocarditis in the presence of prosthetic valves and pacemakers is usually due to staphylococci. We present a case of pacemaker endocarditis caused by Pseudomonas aeruginosa that was successfully treated with a combination of antimicrobial therapy and percutaneous removal of the colonized lead.

The immunological and virological response in human immunodeficiency virus type-1 (HIV-1) infected Indian individuals on haart therapy: A one-year follow up study.

Currently, antiretroviral therapy has become more affordable even in developing countries and it is being used in India. Fifteen HIV-1 infected individuals, who were on highly active antiretroviral therapy (HAART), were followed up for an average period of one year. The plasma viral load and CD4+ T cell estimation done at mean intervals of 5 months and 11 months after initiation of therapy showed a good response to therapy in 14 (93%) individuals.

Antituberculous therapy-induced toxicity.

Antituberculous drugs are generally safe but can occasionally be associated with life-threatening complications. This is a case report of neurotoxicity, acute respiratory distress syndrome (ARDS) and drug fever, occurring in a patient after initiation of antituberculous therapy (ATT).

CD4 counts of normal and HIV-infected south Indian adults: do we need a new staging system?

BACKGROUND: The normal range of CD4 lymphocyte count varies among different ethnic groups. In populations with CD4 counts inherently lower than in the West, the Centers for Disease Control and Prevention (CDC) classification system of HIV-infected individuals may not be appropriate. No such criterion is currently available for ethnic south Indian HIV-infected individuals. We undertook this study to assess the applicability of the western case definition to south Indian HIV patients. METHODS: The CD4 counts of 104 normal and 79 HIV-infected south Indian adults were estimated by flowcytometry. The mean CD4 counts were estimated and compared between CDC groups A, B and C and controls. Receiver operator characteristics curves were generated to determine the cut-off that correlated best with clinical staging for this population. RESULTS: The mean CD4 and CD8 cell counts/microl and the CD4/CD8 ratio of the control group were 799.0, 919.6 and 0.94, respectively. For CDC groups A, B and C, the mean CD4 counts/microl were 454.4, 254.4 and 168; mean CD8 counts/microl were 1156, 1070.9 and 1191.3; and mean CD4/CD8 ratios were 0.44, 0.25 and 0.15, respectively. CONCLUSION: The mean CD4 count among normal south Indians is significantly lower than that in the western population and parallels that of the Chinese. When categorized based on the CDC classification system, the mean CD4 count of HIV-infected individuals was lower. Categories of CD4 counts > 300, 81-300 and < or =80 cells/microl and CD4% > 14, 7-14 and < or = 6 correlate better with disease progression among HIV-infected individuals. A longitudinal study is required before guidelines for the Indian population can be devised.

Enteric pathogens in southern Indian HIV-infected patients with & without diarrhoea.

This study was undertaken to determine the carriage rate of various enteric pathogens in southern Indian patients with HIV infection, both with and without diarrhoea. Stool from 111 consecutive HIV-positive patients (50 without and 61 with diarrhoea) was examined by microscopy and culture. Jejunal biopsy and fluid examination were carried out if diarrhoea persisted, with negative stool examination. Enteric pathogens were detected from stool in 57.4 per cent of diarrhoeal patients compared to 40 per cent of those without diarrhoea (P > 0.05). Jejunal biopsy and fluid examination provided 11 additional diagnoses. Protozoa accounted for 71.8 per cent of all pathogens isolated. Isospora was significantly more common in patients with (11/61) than in those without (2/50) diarrhoea (P < 0.05). Bacterial pathogens were isolated more commonly from patients with diarrhoea (12/61 compared to 2/50, P < 0.05). Isolation rate of pathogens was higher from patients with diarrhoea for more than 2 wk, compared to those with less than 2 wk duration. Remission of diarrhoea either spontaneously or with symptomatic therapy was observed in 22 patients with acute diarrhoea. A high enteric carriage of a number of pathogens was noted in HIV patients without diarrhoea, but I. belli and bacterial enteropathogens were more likely to be associated with diarrhoea.

Predictors of mortality in a medical intensive care unit.

BACKGROUND: Scoring systems to predict mortality in intensive care units have been developed in western populations. There is a need to identify and validate prognostic variables in the Indian context. We compared two scoring systems to predict the discharge outcome in patients admitted to a medical intensive care unit. METHODS: Five hundred patients admitted to a medical intensive care unit were studied prospectively. Modified acute physiology and chronic health evaluation II (APACHE II) score and modified organ system failure (OSF) score were applied on the day of admission to the intensive care unit. The scores obtained by the two systems were compared using the area under the curve approach. The likelihood ratios were calculated for predicting discharge outcome. RESULTS: The modified OSF score predicted discharge outcome better than the modified APACHE II score--receiver operating characteristic curve area (standard error-area) 0.7062 (0.0244) and 0.6068 (0.0267) for the modified OSF and the modified APACHE II scores, respectively. This was statistically significant (p < 0.001). The likelihood ratio for the modified OSF score for different cut-off points varied from 0.27 to 5.49, while the likelihood ratio for the modified APACHE II score varied from 0.11 to 2.08. This means that for an intensive care unit with a 30% overall mortality, the modified OSF score could separate patients with 10% to 70% mortality, while the modified APACHE II score could predict only 5% to 47% mortality. CONCLUSION: The modified OSF score was superior to the modified APACHE II score in predicting mortality in patients admitted to the medical intensive care unit.

Epidemiological features of acquired immunodeficiency syndrome in southern India.

AIDS was diagnosed in 187 men and 24 women (M:F = 8:1) from April 1987 till December 1994 at the Christian Medical College Hospital, Vellore. The doubling time of the occurrence of AIDS cases was 14 months; during 1987-90 there were an average of 5.7 cases per year; in 1991-93 there were 28 per year; in 1994 there were 104 cases. The mean age of patients was 33 yr for men and 31 for women. Among men, the primary mode of infection was heterosexual contact with female commercial sex workers. Among women, the most common source of infection was their husbands. There were 4 bisexuals and one homosexual subject who might have acquired infection by having sex with other men. There were 135 subjects from urban and 76 from rural communities. Most subjects belonged to the lower socio-economic classes. These data show that HIV infection had been very widespread in this region, both urban and rural.

Evaluation of an ELISA for the diagnosis of brucellosis.

Brucela serology using ELISA and standard agglutination test was performed on 23 patients with prolonged fever where the test was requested, on 26 randomly chosen patients with prolonged fever where it was not requested and on 17 controls. ELISA was positive in 39.1, 26.9 and 0 per cent respectively in these groups. Brucellosis may often be unsuspected because of its varied clinical manifestations and may be a more important cause of fever than previously considered. Our data reaffirm that ELISA is superior to the standard agglutination test for the diagnosis of brucellosis.

Melioidosis In India: the tip of the iceberg?

Diagnosis of melioidosis by the isolation of Burkholderia pseudomallei from one or more body fluid/tissue specimens of 6 Indian subjects, 5 of whom had not travelled outside India, is reported. The places of residence of these 6 and one patient previously reported, namely Tripura (2), Kerala (2), Orissa (1), Tamil Nadu (1) and Maharashtra (1) are therefore potentially endemic for melioidosis. B.pseudomallei closely resembles common contaminant Pseudomonas sp. and are easily mis-identified in microbiology laboratories. We surmise that melioidosis is underdiagnosed and underreported in India and we alert clinicians, microbiologists and public health professionals to the possibility of melioidosis being far more common than previously recognised.