BackgroundIndia 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/FindingsRetrospective 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/SignificanceThere 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.

Increasing rates of ESBL producers have been noted, which is alarming. Further, carbapenem resistance was also gradually increasing, which needs much attention. Overall, this study data show that carbapenems, amikacin and colistin continue to be the best agents available to treat drug-resistant infections. Thus continuous monitoring of susceptibility profile of the clinically important Gram-negative pathogens is of great importance to guide effective antimicrobial therapy.

ObjectivesIn rural pregnant Indian women, multiple missed antenatal screening opportunities due to inadequate public health facility-based screening result in undiagnosed HIV and sexually transmitted bloodborne infections (STBBIs) and conditions (anaemia). Untreated infections complicate pregnancy management, precipitate adverse outcomes and risk mother-to-child transmission. Additionally, a shortage of trained doctors, rural women’s preference for home delivery and health illiteracy affect health service delivery. To address these issues, we developed AideSmart!, an innovative, app-based, cloud-connected, rapid screening strategy that offers multiplex screening for STBBIs and anaemia at the point of care. It offers connectivity, integration, expedited communications and linkages to clinical care throughout pregnancy.MethodsIn a cross-sectional study, we evaluated the AideSmart! strategy for feasibility, acceptability, preference and impact. We trained 15 healthcare professionals (HCPs) to offer the AideSmart! strategy to 510 pregnant women presenting for care to outreach rural service units of Christian Medical College, Vellore, India.ResultsWith the AideSmart! screening strategy, we recorded an acceptability of 100% (510/510), feasibility (completion rate) of 91.6% (466/510) and preference of 73%. We detected 239 infections/conditions (239/510, 46.8%) at the point-of-care, of which 168 (168/239; 70%) were lab confirmed, staged and treated rapidly. Of the 168 confirmed infections/conditions, 127 were anaemia, 11 Trichomonas and 30 hepatitis B virus (HBV) (25 resolved naturally, 5 active infections). Four infants (4/5; 80%) were prophylaxed for HBV and were declared disease-free at 9 months. Recruited participants were young; mean age was 24 years (range: 17–40) and 74% (376/510) were in their second trimester. Furthermore, 95% of the participants were retained throughout their pregnancy.ConclusionThe AideSmart! strategy was deemed feasible to operationalise by HCPs. It was accepted and preferred by participants, resulting in timely screening and treatment of HIV/STIs and anaemia, preventing mother-to-child transmission. The strategy could be reverse-innovated to any context to maximise its health impact.

Fosfomycin exhibits good in vitro activity against both the uropathogens tested. Therefore, it might be considered as a treatment option for urinary tract infections in India; however, clinical trials should first reinforce the in vitro findings.

Oral amoxicillin/clavulanate is a community workhorse antibiotic, routinely prescribed for respiratory tract infections, skin infections as well as urinary tract infections (UTIs). Multiple adult and paediatric dose formulations of amoxicillin/clavulanate are available in different parts of the world. In adult formulations, clavulanic acid dose is restricted to 125 mg because of tolerability issues. Despite its popular use for 40 years, few pharmacokinetic/pharmacodynamic (PK/PD) studies were undertaken to justify the doses and breakpoints currently in use for various infections. Clavulanate has a minimal role in the combination’s use for respiratory infections. In the context of rising extended spectrum beta-lactamase (ESBL) prevalence globally, empirical and overuse of orally administered amoxicillin/clavulanate may select resistance in Gram-negative pathogens. The susceptibility test methods and interpretive criteria differ between the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST). Third-generation oral cephalosporins such as ceftibuten or cefpodoxime can be combined with amoxicillin/clavulanate to tackle UTIs involving ESBL producing Escherichia coli and Klebsiella spp. Clinicians who routinely prescribe amoxicillin/clavulanate in outpatient settings should be aware of potential benefits and limitations of this combination.

The treatment of urinary tract infections (UTIs) has been complicated by the emergence of multidrug-resistant, b-lactamase-expressing pathogens. As a result of the limited treatment options, patients often require hospitalization and intravenous therapy. In essence, a strong unmet need for oral antibiotics, active against extended-spectrum b-lactamase (ESBL) uropathogens has emerged. Oral carbapenems (tebipenem and sulopenem) and oral cephalosporin/b-lactamase inhibitor combinations are in various stages of clinical development for the treatment of uncomplicated and complicated UTI. Tebipenem, if approved, will be the first oral treatment for complicated UTI while sulopenem will be for uncomplicated UTI. The b-lactamase inhibitors ETX0282, VNRX7145, ARX1796, and QPX7728 are combined with cefpodoxime proxetil or ceftibuten that achieve favorable exposures in urine compared to other uropathogen-active oral cephalosporins.The combination ceftibuten-QPX7728 has potential broad-spectrum coverage against carbapenemase producers including metallo b-lactamase producers. Other novel combinations, namely cefpodoxime/ETX0282, ceftibuten/VNRX-7145, and ceftibuten/ ARX1796, have also demonstrated excellent activity against Klebsiella pneumoniae carbapanemase (KPC) and OXA-48-like producers. All these agents, upon their arrival for commercial use, would strengthen the outpatient therapy.

Objective:To estimate the prevalence of group B Streptococcus (GBS) carriage among pregnant women attending the antenatal clinic, and the colonization rates among newborn born to colonized mothers.Material and Methods:Women attending the antenatal clinic between 35-37 weeks were screened using rectal and lower vaginal swab. Swabs were initially plated on sheep blood agar and LIM broth. The LIM broth was subcultured after 24 hours onto blood agar and CHROMagar StrepB plates with all plates checked for growth at 24 and 48 hours. All babies born to mothers in the study had surface swabs taken to estimate the vertical transmission rate.Results:Between September 2012 and March 2013, 305 consecutive mothers were screened. Of these, eight mothers were GBS positive in 5% blood agar (2.6%) and 23 mothers showed GBS positivity in enriched media (7.6%). Sixteen of 238 babies (6.7%) were colonized.Conclusion:Though lower than rates from most countries, 7.6% of mothers attending an antenatal clinic in south India were colonized with GBS. Use of enrichment media markedly increased the detection rate. Approximately two-thirds of newborn born to colonized mothers were also colonized. There were no instances of invasive GBS disease, indirectly proving the efficacy of intrapartum prophylaxis in preventing neonatal GBS disease.

ObjectivesTo determine the in vitro activity of antibiotics, including arbekacin, cefminox, fosfomycin and biapenem which are all still unavailable in India, against Gram-negative clinical isolates.MethodsWe prospectively collected and tested all consecutive isolates of Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa and Acinetobacter spp. from blood, urine and sputum samples between March and November 2012. The minimum inhibition concentration (MIC) of 16 antibiotics was determined by the broth micro-dilution method.ResultsOverall 925 isolates were included; 211 E. coli, 207 Klebsiella spp., 153 P. aeruginosa, and 354 Acinetobacter spp. The MIC50 and MIC90 were high for cefminox, biapenem and arbekacin for all pathogens but interpretative criteria were not available. The MIC50 was categorized as susceptible for a couple of antibiotics, including piperacillin/tazobactam, carbapenems and amikacin, for E. coli, Klebsiella spp. and P. aeruginosa. However, for Acinetobacter spp., the MIC50 was categorized as susceptible only for colistin. On the other hand, fosfomycin was the only antibiotic that inhibited 90% of E. coli and Klebsiella spp. isolates, while 90% of P. aeruginosa isolates were inhibited only by colistin. Finally, 90% of Acinetobacter spp. isolates were not inhibited by any antibiotic tested.ConclusionFosfomycin and colistin might be promising antibiotics for the treatment of infections due to E. coli or Klebsiella spp. and P. aeruginosa, respectively, in India; however, clinical trials should first corroborate the in vitro findings. The activity of tigecycline should be evaluated, as this is commonly used as last-resort option for the treatment of multidrug-resistant Acinetobacter infections.