Renu Bharadwaj

The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4–6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8–19). HIV infection (aIRR = 29.08, 95% CI: 2.38–355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89–20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.

Influenza-like illness (ILI) and acute respiratory infection (ARI) are common presentations during winter, and indiscriminate antibiotic use contributes significantly to the emerging post-antibiotic era. Although viral agents causing ILI are predominant, they are indistinguishable from the bacterial agents based on the clinical features alone. The present study was aimed at determining the bacterial agents associated with ILI and their susceptibility pattern during a study done in a community setting in Pune during a surveillance of ILI between March 2013 to November 2016. Throat swabs from 512 suspected ILI cases were processed, and organisms were identified by the standard conventional method. An antimicrobial susceptibility testing was done as per the Clinical Laboratory Standard Institute (CLSI) guidelines. The patients comprised 238 males and 274 females with the majority (38.7%) in the age group of ≤10 years. Bacteria could be isolated from 9.8 % of the patients. The predominant bacteria included beta-hemolytic Streptococcus (42%) followed by group G Streptococcus (30%) and group A Streptococcus (20%). All organisms were sensitive to Penicillin except two isolates of Staphylococcus aureus (50%). Tetracycline (98.8%) and ciprofloxacin (87%) were the next most effective drugs. Overall resistance was observed for erythromycin (37%) and co-trimoxazole (32%).

Healthcare exposure may increase drug-resistant Enterobacteriaceae colonization risk. Nascent antimicrobial stewardship efforts in low- and middle-income countries require setting-specific data. We aimed to evaluate risk factors for inpatient drug resistant Enterobacteriaceae colonization in a resource-limited setting in India. Patients age ≥ 6 months admitted with ≥24 h of fever to a tertiary hospital in Pune, India were enrolled in a prospective cohort. Perirectal swabs, collected on admission and hospitalization day 3 or 4, were cultured in vancomycin- and ceftriaxone-impregnated media to assess for ceftriaxone-resistant Enterobacteriaceae (CTRE) and carbapenem-resistant Enterobacteriaceae (CPRE). Multivariable analyses assessed risk factors for drug-resistant Enterobacteriaceae colonization among participants without admission colonization. Admission perirectal swabs were collected on 897 participants; 87 (10%) had CTRE and 14 (1.6%) had CPRE colonization. Admission CTRE colonization was associated with recent healthcare contact (p < 0.01). Follow-up samples were collected from 620 participants, 67 (11%) had CTRE and 21 (3.4%) had CPRE colonization. Among 561 participants without enrollment CTRE colonization, 49 (9%) participants were colonized with CTRE at follow-up. Detection of CTRE colonization among participants not colonized with CTRE at admission was independently associated with empiric third generation cephalosporin treatment (adjusted odds ratio [OR] 2.9, 95% CI 1.5–5.8). Follow-up transition to CPRE colonization detection was associated with ICU admission (OR 3.0, 95% CI 1.0–8.5). Patients who receive empiric third generation cephalosporins and are admitted to the ICU rapidly develop detectable CTRE and CPRE colonization. Improved antimicrobial stewardship and infection control measures are urgently needed upon hospital admission.

Acute febrile illness (AFI) is a major cause of morbidity and mortality in India and other resource-limited settings, yet systematic etiologic characterization of AFI has been limited. We prospectively enrolled adults (N = 970) and children (age 6 months to 12 years, N = 755) admitted with fever from the community to Sassoon General Hospital in Pune, India, from July 2013 to December 2015. We systematically obtained a standardized clinical history, basic laboratory testing, and microbiologic diagnostics on enrolled participants. Results from additional testing ordered by treating clinicians were also recorded. A microbiological diagnosis was found in 549 (32%) participants; 211 (12%) met standardized case definitions for pneumonia and meningitis without an identified organism; 559 (32%) were assigned a clinical diagnosis in the absence of a confirmed diagnosis; and 406 (24%) had no diagnosis. Vector-borne diseases were the most common cause of AFI in adults including dengue (N = 188, 19%), malaria (N = 74, 8%), chikungunya (N = 15, 2%), and concurrent mosquito-borne infections (N = 23, 2%) occurring most frequently in the 3 months after the monsoon. In children, pneumonia was the most common cause of AFI (N = 214, 28%) and death. Bacteremia was found in 68 (4%) participants. Central nervous system infections occurred in 58 (6%) adults and 64 (8%) children. Etiology of AFI in India is diverse, highly seasonal, and difficult to differentiate on clinical grounds alone. Diagnostic strategies adapted for season and age may reduce diagnostic uncertainty and identify causative organisms in treatable, fatal causes of AFI.

SETTING: Pune, India.OBJECTIVES: To estimate the prevalence and risk factors of pre-diabetes mellitus (DM) and DM, and its associations with the clinical presentation of tuberculosis (TB).DESIGN: Screening for DM was conducted among adults (age  18 years) with confirmed TB between December 2013 and January 2017. We used multinomial regression to evaluate the risk factors for pre-DM (glycated hemoglobin [HbA1c]  5.7–6.5% or fasting glucose 100–125 mg/dl) and DM (HbA1c  6.5% or fasting glucose  126 mg/dl or random blood glucose > 200 mg/dl or self-reported DM history/treatment) and the association of dysglycemia with the severity of TB disease.RESULTS: Among 1793 participants screened, 890 (50%) had microbiologically confirmed TB. Of these, 33% had pre-DM and 18% had DM; 41% were newly diagnosed. The median HbA1c level among newly diagnosed DM was 7.0% vs. 10.3% among known DM (P < 0.001). DM (adjusted OR [aOR] 4.94, 95%CI 2.33–10.48) and each per cent increase in HbA1c (aOR 1.42, 95%CI 1.01–2.01) was associated with >1+ smear grade or 9 days to TB detection. CONCLUSION: Over half of newly diagnosed TB patients had DM or pre-DM. DM and increasing dysglycemia was associated with higher bacterial burden at TB diagnosis, potentially indicating a higher risk of TB transmission to close contacts.

Background and Objectives: The resistance of uropathogens to commonly prescribed antimicrobials is increasing globally. As the susceptibility of uropathogens varies according to place and time, the present study was undertaken to know the local epidemiology and antimicrobial susceptibility patterns (AMSP) of common bacterial uropathogens. This helps in formulating effective empirical treatment. Methods: This is a prospective observational study, where a total of 3353 consecutive urine specimens over a period of one year in a tertiary care hospital were cultured by semiquantitative method. The pathogens isolated were identified by standard methods and their antimicrobial susceptibility was done by Kirby Bauer disk diffusion method as per Clinical Laboratory Standards Institute (CLSI) guidelines. The data was analyzed by using WHONET 5.6 software. Results: Of the total 3353 samples, 63% were sterile, 24% showed significant growth, 5.27% showed insignificant growth and 7.45% were collection contaminants. The 812 samples with significant growth yielded 988 bacterial isolates with 814 (82%) gram negative bacilli (GNB) and 174 (18%) gram positive cocci (GPC). Gram negative uropathogens had low susceptibility to ampicillin, cotrimoxazole, norfloxacin and cephalosporins. They had good susceptibility to nitrofurantoin and aminoglycosides like amikacin, gentamicin followed by piperacillin-tazobactam and meropenem. ESBL production was observed amongst 40% of Escherichia coli and 60% of Klebiella pneumoniae isolates. Similarly gram positive uropathogens had low susceptibility to fluoroquinolones like norfloxacin, ciprofloxacin and tetracycline. They had good susceptibility to vancomycin, teicoplanin, linezolid and nitrofurantoin. Amongst the isolates from In Patient department (IPD) 36% of Staphylococcus aureus were MRSA and 2% of Enterococcus were Vancomycin Resistant Entercoccus (VRE). Conclusion: Local epidemiology and susceptibility pattern of uropathogens should be studied to formulate effective empirical treatment regimen. Our study recommends use of Nitrofurantoin as best antimicrobial for UTI in uncomplicated, non-hospitalised patients. And use of aminoglycosides, or β lactam - βlactamase inhibitor combination agents like piperacillin/tazobactum and cefaperazone-sulbactam in complicated and serious hospitalized patients.