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

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

An evaluation of the role of noninvasive positive pressure ventilation in the management of acute respiratory failure in a developing country

Objective: Noninvasive positive pressure ventilation (NIPPV) has been shown to decrease the need for invasive mechanical ventilation (MV) in patients presenting with acute respiratory failure (ARF). We conducted a prospective study to assess if NIPPV use, in a developing country, was associated with clinical and physiological improvements. Design: Prospective observational study. Materials and Methods: Forty patients admitted to a medical intensive care unit during a 2-year period who fulfilled criteria for inclusion formed the study cohort to receive NIPPV. Findings: Baseline (mean ± SD) pH, PaCO 2 and PaO 2 were 7.25 ± 0.08, 76.6 ± 20.9 and 79.18 ± 40.56 mmHg respectively. The primary indication for NIPPV was hypercapnic respiratory failure (n = 36, 90%). The success rate with NIPPV was 85%, with 34 of 40 patients weaned successfully. Significant improvements were observed at 1 hour following institution of NIPPV in pH (7.31 ± 0.09, P < 0.001) and PaCO 2 (65 ± 17.9, P < 0.001). These improvements continued up to the time of weaning (pH 7.38 ± 0.08, PaCO 2 54.7 ± 20) and maintained (within 12 h) postweaning from the ventilator (pH 7.39 ± 0.08, PaCO 2 51.9 ± 12.4). No significant change in the PaO 2 was observed during NIPPV; PaO 2 after 1 h, prior to weaning and after weaning was 90.53 ± 42.85, 84.80 ± 33.76, 78.71 ± 43.81 respectively. Conclusion: This study has demonstrated benefits of NIPPV in avoiding the need for invasive MV in patients presenting with ARF of diverse etiology, with results comparable to developed nations. Increased use of NIPPV in ARF is likely to impact favorably in nations with limited resources

Enterococcal Bacteremia is Associated with Prolonged Stay in the Medical Intensive Care Unit

Background: Although enterococci are relatively common nosocomial pathogens in surgical intensive care units (ICUs), their significance in blood cultures from patients in the medical ICU is unclear. Materials and Methods: In this retrospective study spanning 2 years, the clinical and microbiological characteristics of enterococcal bacteremia among medical ICU patients were evaluated. Results: Of 1325 admissions, 35 with enterococcal bacteremia accounted for 14.8% of positive blood cultures. They were significantly older (P=0.03) and had various co-morbidities. Most had vascular (96.9%) and urinary (85.3%) catheters, and 67.7% were mechanically ventilated. In addition to blood, enterococci were isolated from vascular catheters (8.6%) and other sites (20%), while no focus was identified in 77% of patients. Prior use of broad-spectrum antimicrobials was nearly universal. All isolates tested were sensitive to vancomycin and linezolid. Resistance to ampicillin and gentamicin were 44.7% and 52.6%, respectively. Compared with other medical ICU patients, patients with enterococcal bacteremia had a longer ICU stay (P<0.0001) and a trend toward higher ICU mortality (P=0.08). Conclusions: Enterococcal bacteremia is an important nosocomial infection in the medical ICU, with a predilection for older patients with multiple comorbidities. Its occurrence is associated with a significantly longer ICU stay and a trend to a higher mortality. The choice of antibiotics should be dictated by local susceptibility data

Recruitment.

<p>Recruitment.</p

Description of Cases.

<p>*More than 20% data unavailable.</p