Prevalence and factors associated with inappropriate continuation of stress ulcer prophylaxis at discharge.

Stress ulcer prophylaxis is started in the critical care unit to decrease the risk of upper gastrointestinal ulcers in critically ill persons and to decrease mortality caused by stress ulcer complications. Unfortunately, the drugs are often continued after recovery through discharge, paving the way for unnecessary polypharmacy. STUDY DESIGN: We conducted a retrospective cross-sectional study including patients admitted to the adult critical care unit and started on the stress ulcer prophylaxis with a proton pump inhibitor (PPI) or histamine receptor 2 blocker (H2 blocker) with an aim to determine the prevalence of inappropriate continuation at discharge and associated factors. RESULT: 3200 people were initiated on stress ulcer prophylaxis, and the medication was continued in 1666 patients upon discharge. Indication for long-term use was not found in 744 of 1666, with a 44% prevalence of inappropriate continuation. A statistically significant association was found with the following risk factors: discharge disposition (home vs other medical facilities, p=0.002), overall length of stay (more than 10 days vs less than or equal to 10 days, p<0.0001), mechanical ventilator use (p<0.001), number of days on a mechanical ventilator (more than 2 days vs less than or equal to 2 days, p<0.001) and class of stress ulcer prophylaxis drug used (H2 blocker vs PPI, p<0.001). CONCLUSION: The prevalence of inappropriate continuation was found to be higher than prior studies. Given the risk of unnecessary medication intake and the associated healthcare cost, a web-based quality improvement initiative is being considered.

Predictors of Change in the Anemia Status Among Pulmonary Tuberculosis Patients Following Anti-tuberculosis Treatment in Puducherry, India.

Background Pulmonary tuberculosis (PTB) is commonly associated with reversible peripheral blood abnormalities. The evolution of tuberculosis (TB)-associated anemia with anti-tuberculosis treatment (ATT) has not been well elucidated. This study aimed to compare the hematological profiles at the start and end of the ATT among new sputum smear-positive (NSP) PTB patients in Puducherry, India. Methods A prospective cohort study was conducted in the 10 urban primary health centers of Puducherry from 2017 to 2020. All the NSP PTB participants aged ≥18 years registered under the National Tuberculosis Elimination Program (NTEP) were contacted within two weeks of the start of the ATT. All eligible participants were enrolled, and they were followed up till the end of ATT (180 days). Hematological profiles and anthropometric measurements were compared at the start and end of the ATT. Binomial logistic regression analysis was used to assess the predictors of changes in the anemia status at the start and end of the ATT. Results Out of 176 NSP PTB participants, 145 were followed up after treatment. Initially, 63% (111/176) patients had anemia, which decreased to 44% (64/145) by the end of treatment. The risk factors for a negative change in hemoglobin levels were female gender, below poverty level, underweight, and reduced iron intake. The adjusted risk ratios (ARRs) were 1.53 (1.24-1.88), 1.18 (1.01-1.38), 1.29 (1.02-1.64), and 1.26 (1.05-1.51),respectively. Conclusion ATT may lead to the resolution of TB-associated anemia. Moreover, female gender, possession of a red ration card, being underweight, and reduced iron intake were identified as risk factors for negative changes in hemoglobin levels during treatment.

Development and Validation of a Parsimonious Tuberculosis Gene Signature Using the digital NanoString nCounter Platform.

BACKGROUND: Blood-based biomarkers for diagnosing active tuberculosis (TB), monitoring treatment response, and predicting risk of progression to TB disease have been reported. However, validation of the biomarkers across multiple independent cohorts is scarce. A robust platform to validate TB biomarkers in different populations with clinical end points is essential to the development of a point-of-care clinical test. NanoString nCounter technology is an amplification-free digital detection platform that directly measures mRNA transcripts with high specificity. Here, we determined whether NanoString could serve as a platform for extensive validation of candidate TB biomarkers. METHODS: The NanoString platform was used for performance evaluation of existing TB gene signatures in a cohort in which signatures were previously evaluated on an RNA-seq dataset. A NanoString codeset that probes 107 genes comprising 12 TB signatures and 6 housekeeping genes (NS-TB107) was developed and applied to total RNA derived from whole blood samples of TB patients and individuals with latent TB infection (LTBI) from South India. The TBSignatureProfiler tool was used to score samples for each signature. An ensemble of machine learning algorithms was used to derive a parsimonious biomarker. RESULTS: Gene signatures present in NS-TB107 had statistically significant discriminative power for segregating TB from LTBI. Further analysis of the data yielded a NanoString 6-gene set (NANO6) that when tested on 10 published datasets was highly diagnostic for active TB. CONCLUSIONS: The NanoString nCounter system provides a robust platform for validating existing TB biomarkers and deriving a parsimonious gene signature with enhanced diagnostic performance.

Tuberculosis screening among pregnant women attending a tertiary care hospital in Puducherry, South India: is it worth the effort?

BACKGROUND: The national tuberculosis (TB) programme in India recommends screening all pregnant women for TB, but this is rarely implemented. We carried out systematic TB screening among women attending the antenatal clinic of a tertiary care hospital in Puducherry, South India, during February to April 2018. OBJECTIVE: To assess the number screened and number (proportion) with presumptive and active TB, and understand potential implementation from the healthcare providers' perspective. METHODS: We conducted a mixed-methods study. The quantitative phase was a cross-sectional study including 4203 pregnant women. Data were captured using a structured proforma. Any of the following symptoms constituted 'presumptive TB': any cough, haemoptysis, fever, weight loss, night sweats, neck swellings, joint pains, neck stiffness and disorientation. Those screening positive were referred for investigations and evaluation by a chest physician. The qualitative phase involved seven one-to-one interviews with healthcare providers. Manual thematic analysis was performed to generate themes. RESULTS: Among 4203 women (two HIV-positive) screened, 77 (1.8%) had presumptive TB. Cough was the predominant symptom (n = 75). Only 12 women could produce a sputum sample, of whom one (0.02%) was diagnosed with active TB by the Xpert MTB/RIF assay. Challenges cited by healthcare providers were lack of awareness among clients and providers, high case load, lack of dedicated staff, perception that TB screening is a low-yield, low-priority activity and losses in the referral process. Suggested solutions were providing dedicated staff and space for screening, educating women to self-report using posters and videos, and creating a one-stop care provision. CONCLUSIONS: The TB yield among pregnant women was very low, calling into question the value of systematic screening in a low-HIV setting. However, the findings may not be generalizable. Evidence is urgently needed from primary and secondary care facilities. The challenges and solutions identified may help in optimizing the screening process.

Existing blood transcriptional classifiers accurately discriminate active tuberculosis from latent infection in individuals from south India.

Several studies have identified blood transcriptomic signatures that can distinguish active from latent Tuberculosis (TB). The purpose of this study was to assess how well these existing gene profiles classify TB disease in a South Indian population. RNA sequencing was performed on whole blood PAXgene samples collected from 28 TB patients and 16 latently TB infected (LTBI) subjects enrolled as part of an ongoing household contact study. Differential gene expression and clustering analyses were performed and compared with explicit predictive testing of TB and LTBI individuals based on established gene signatures. We observed strong predictive performance of TB disease states based on expression of known gene sets (ROC AUC 0.9007-0.9879). Together, our findings indicate that previously reported classifiers generated from different ethnic populations can accurately discriminate active TB from LTBI in South Indian patients. Future work should focus on converting existing gene signatures into a universal TB gene signature for diagnosis, monitoring TB treatment, and evaluating new drug regimens.

Cerebrospinal fluid matrix metalloproteinase 9 levels, blood-brain barrier permeability, and treatment outcome in tuberculous meningitis.

OBJECTIVES: Tuberculous meningitis is characterized by elevated levels of matrix metalloproteinase 9 (MMP9) in the cerebrospinal fluid (CSF). However, it is unclear whether elevated MMP9 levels are associated with poor treatment outcome. We tested the hypothesis that pretreatment MMP9 levels in the CSF would be higher in tuberculous meningitis patients experiencing a poor treatment outcome. METHODS: We prospectively assessed the treatment outcome in a consecutive sample of human immunodeficiency virus-negative patients with tuberculous meningitis. We defined good outcome as survival without severe neurological disability (modified Rankin scale scores 0-2). We estimated levels of MMP9 and its tissue inhibitor (TIMP1) on pretreatment CSF samples. We used albumin index to assess blood-brain barrier permeability. RESULTS: We studied 40 patients (23 males [58%]) with tuberculous meningitis. Sixteen patients (40%) had stage 3 disease. On follow-up, 18 (45%) patients had a poor treatment outcome-15 patients died and 3 had severe neurological disability. Pretreatment MMP9 levels were not associated with treatment outcome (median [interquartile range], 254 [115-389] vs. 192 [60-383] ng/mL in good vs. poor outcome groups; P = 0.693). MMP9 levels did not correlate with the albumin index (Spearman's rho = 0.142; P = 0.381). However, MMP9 levels significantly correlated with CSF glucose levels (rho = -0.419; P = 0.007) and admission Glasgow coma scale score (rho = 0.324; P = 0.032). Likewise, TIMP1 levels also did not differ by treatment outcome (1239 [889-1511] vs. 1522 [934-1949] ng/mL; P = 0.201). MMP9/TIMP1 ratio that reflects net proteolytic activity was also not different between the two groups (0.191 [0.107-0.250] vs. 0.163 [0.067-0.34]; P = 0.625). CONCLUSION: Our findings do not support the hypothesis that pretreatment levels of MMP9 would be higher in tuberculous meningitis patients experiencing a poor treatment outcome. Further, MMP9 levels in the CSF did not correlate with blood-brain barrier permeability in patients with tuberculous meningitis.

Prevalence of Clostridium difficile infection among the patients attending a tertiary care teaching hospital.

BACKGROUND: Clostridium difficile, a most important nosocomial enteric pathogen, is recognized globally as responsible for antibiotic-associated diarrhea and colitis. It is associated with considerable morbidity and mortality due to widespread use of antibiotics. AIMS: The study was done to determine the prevalence of C. difficile infection (CDI) among the patients attending a tertiary care teaching hospital in Puducherry. SETTINGS AND DESIGN: We performed a prospective cohort study in Mahatma Gandhi Medical College and Research Institute. MATERIALS AND METHODS: Around 150 patients were evaluated along with the patient details. C. difficile toxin detection was done as per the standard algorithm using the C. Diff Quik Chek Complete® assay (TECHLAB, Blacksburg, VA, USA). STATISTICAL ANALYSIS USED: Analysis was done using statistics software (SPSS 16.0, SPSS Inc., Chicago, IL, USA). RESULTS: The prevalence of CDI was found to be 4%. More toxin-positive cases were between 50 and 60 years of age, and there was no difference in gender. Intensive Care Unit showed more toxin-positive cases; however, there was no significant association between the occurrence of CDI and the primary diagnosis of the patients. CONCLUSIONS: The prevalence of CDI in our hospital was found to be 4%, which was relatively lower compared to other Indian studies. However, awareness of the risk factors may assist in identifying patients at higher risk for CDI, guide implementation of appropriate preventive measures, and modulate potential intervention measure during management.

Role of Appropriate Therapy in Combating Mortality among the Ventilated Patients.

CONTEXT: Ventilator associated pneumonia (VAP) is a nosocomial infection prevalent among the intensive care unit (ICU) patients despite proper infection control practices. The diagnosis of VAP still remains controversial and hence the mortality rate is higher among this group of patients. AIM: The aim of our study was to identify the antibiotic pattern and the appropriateness of treatment followed in the ICU in relation with the clinical pulmonary infection score (CPIS) as a tool to diagnose VAP. This was compared with patients who had an inappropriate treatment in comparison to the CPIS and the clinical outcome. RESULTS: Out of the 18 VAP patients, 12 (66.7%) received appropriate therapy based on the antibiotic susceptibility pattern of the causative organism, while 1 (5.5%) received partially inappropriate therapy and 5 (27.8%) received totally inappropriate therapy. Nine of the 18 (50%) VAP patients died, while only 5 of the 58 (8.6%) patients without VAP died. 72.2% patients with VAP received appropriate treatment based on the sensitivity of the isolates. The mortality rate in VAP patients receiving inappropriate therapy was 80%, while in those receiving appropriate therapy the mortality rate was 38.5%. The mortality rate among VAP patients with blood culture positivity was 100%, while it was 43.75% among those with negative blood culture. CONCLUSION: The mortality rate among the patients receiving inappropriate therapy is high compared to other group of patients. Hence, a proper evaluation and administration of appropriate antibiotics can curb mortality among the ventilated patients.

Bacteriophage types of methicillin-resistant Staphylococcus aureus in a tertiary care hospital.

BACKGROUND: Phage typing had been utilised extensively to characterise methicillin-resistant Staphylococcus aureus (MRSA) outbreak strains in the past. It is an invaluable tool even today to monitor emergence and dissemination of MRSA strains. AIMS: The aim of this study was to determine the prevalent phage types of MRSA in south India and the association between phage types, antibiotic resistance pattern and risk factors. METHOD: A total of 48 non-duplicate MRSA strains recovered from various clinical samples during January to December, 2010 were tested against a panel of anti-staphylococcal antibiotics. Phage typing was carried out at the National Staphylococcal Phage Typing Centre, New Delhi. Out of 48, 32 hospitalised patients were followed up for risk factors and response to empirical and post sensitivity antibiotic therapy. The risk factors were compared with a control group of 30 patients with methicillin sensitive Staphylococcus aureus (MSSA) infection. RESULTS: Amongst the five prevalent phage types, 42E was most common (52%), followed by a non-typable variant (22.9%), 42E/47/54/75 (16.6%), 42E/47 (6.2%) and 47 (2%). Phage type 42E was the predominant strain in all wards and OPDs except in the ICU where 42E/47/54/75 was most common. Although not statistically significant, strain 42E/47/54/75 (n=8) showed higher resistance to all drugs, except ciprofloxacin and amikacin, and were mostly D-test positive (87.5%) compared to the 42E strain (32%). Duration of hospital stay, intravenous catheterisation and breach in skin were the most significant risk factors for MRSA infection. CONCLUSION: We found MRSA strain diversity in hospital wards with differences in their antibiotic susceptibility pattern. The findings may impact infection control and antibiotic policy significantly.

Aetiological agents of ventilator-associated pneumonia and its resistance pattern - a threat for treatment.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a common type of nosocomial pneumonia encountered in intensive care units. There are several aetiological agents which make treatment challenging. Improper antibiotic treatment of ventilated patients may lead to the emergence of multidrug resistant (MDR) pathogens. METHOD: A prospective study was performed over a period of 20 months. Our study had two arms: the first, 'Incidence and risk factors of VAP in a tertiary care hospital' was the subject of an earlier publication; we therefore present the second investigative arm in this work. The aetiological agents of patients on mechanical ventilation (MV) were identified by standard bacteriological method. The susceptibility pattern was evaluated by Kirby-Bauer disc diffusion method. Extended spectrum beta lactamase (ESBL) testing was performed by combination disc method, and metallo-beta lactamase (MBL) testing was performed by EDTA disk synergy test (EDS). RESULTS: Late-onset VAP was associated with Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli, while early-onset VAP was commonly caused by members of Enterobacteriaceae, Candida albicans and Staphylococcus aureus. 72.2 per cent of VAP patients had monomicrobial and 27.8 per cent had polymicrobial infection. Out of the 24 isolates obtained from patients with VAP, seven (29.2 per cent) were MDR pathogens. ESBL and MBL production was detected in 40 per cent and 20 per cent of Klebsiella pneumoniae isolated in our study. Around 50 per cent of isolates associated with late-onset VAP were MDR, while 22.2 per cent isolates obtained from patients with earlyonset VAP were MDR. CONCLUSION: VAP is a nosocomial pneumonia that is common among ventilated patients. The aetiological agents vary from common organisms to MDR pathogens that are difficult to treat. A proper knowledge of MDR pathogens and early isolation followed by prevention of prolonged antibiotic therapy can reduce the mortality of late onset VAP.

Incidence and risk factors of ventilator associated pneumonia in a tertiary care hospital.

BACKGROUND: Ventilator associated pneumonia (VAP) is a type of nosocomial pneumonia associated with increased morbidity and mortality. Knowledge about the incidence and risk factors is necessary to implement preventive measures to reduce mortality in these patients. METHOD: A prospective study was conducted at a tertiary care teaching hospital for a period of 20 months from November 2009 to July 2011. Patients who were on mechanical ventilation (MV) for more than 48 hours were monitored at frequent intervals for development of VAP using clinical and microbiological criteria until discharge or death. RESULTS: Of the 76 patients, 18 (23.7%) developed VAP during their ICU stay. The incidence of VAP was 53.25 per 1,000 ventilator days. About 94% of VAP cases occurred within the first week of MV. Early-onset and late-onset VAP was observed in 72.2% and 27.8%, respectively. Univariate analysis showed chronic lung failure, H2 blockers usage, and supine head position were significant risk factors for VAP. Logistic regression revealed supine head position as an independent risk factor for VAP. CONCLUSION: VAP occurred in a sizeable number of patients on MV. Chronic lung failure, H2 blockers usage, and supine head position were the risk factors associated with VAP. Awareness about these risk factors can be used to inform simple and effective preventive measures.

Keratomycosis caused by Exserohilum rostratum.

We report a case of keratomycosis caused by Exserohilum rostratum. A 46-year-old farmer presented with history of pain, watery discharge and redness of the right eye for the past 2 weeks following trauma with vegetable matter. On ocular examination, a central corneal ulcer of about 8 mm with a greyish-white slough, feathery edges and diffuse corneal edema was seen in the right eye. KOH examination of corneal scrapings revealed thick, brown, branched, septate hyphae. Culture of corneal scrapings on Sabouraud dextrose agar showed velvety greenish-black colony with a black pigment on the reverse. The culture was identified as E. rostratum on the basis of microscopic morphology. The patient responded well to treatment with topical natamycin and oral itraconazole.

Detection of extended spectrum beta lactamases, ampc beta lactamases and metallobetalactamases in clinical isolates of ceftazidime resistant Pseudomonas Aeruginosa

We studied the prevalence of ceftazidime resistance in Pseudomonas aeruginosa and the rates of extended-spectrum β-lactamase (ESBL), AmpC β-lactamase (AmpC) and metallo-β-lactamase (MBL) production among the ceftazidime resistant Pseudomonas aeruginosa. A very high rate of MBL production was observed, which suggested it to be an important contributing factor for ceftazidime resistance among Pseudomonas aeruginosa.

Reliability of Kirby-Bauer disk diffusion method for detecting meropenem resistance among non-fermenting gram-negative bacilli.

BACKGROUND: Meropenem is empirically used as a last resort for the treatment of infections by non-fermenting gram-negative bacilli (NFGNB). Minimum inhibitory concentration (MIC) determined using agar or broth dilution methods is widely used for testing meropenem resistance. However, it is not possible in resource-poor settings. AIM: A prospective study was performed to evaluate the reliability of Kirby-Bauer disk diffusion (KBDD) method for detecting meropenem resistance among NFGNB. MATERIALS AND METHODS: A total of 146 NFGNB consisting of 56 Acinetobacter baumannii, 24 Acinetobacter lwoffii, 48 Pseudomonas aeruginosa and 18 Pseudomonas spp. were included in the study. All the isolates were tested simultaneously by both KBDD method and agar dilution method. RESULTS: Very major errors were not observed with A. baumannii, A. lwoffii and P. aeruginosa, while other Pseudomonas spp. showed a very major error rate of about 5.6%. The major error rates observed with A. baumannii, A. lwoffii, P. aeruginosa and Pseudomonas spp. were 1.8%, 0%, 2.1% and 28.6%, respectively. All the isolates showed a good correlation between zone diameters (KBDD method) and MICs (agar dilution method). The sensitivity and specificity of KBDD method for detecting meropenem resistance was above 90% for all the NFGNB except Pseudomonas spp. CONCLUSIONS: The KBDD method can be reliably used for routine testing of meropenem resistance in A. baumannii, A. lwoffii and P. aeruginosa. However, further studies are needed before employing this technique for detecting meropenem resistance in Pseudomonas spp.

Detection of extended spectrum beta lactamases, ampc beta lactamases and metallobetalactamases in clinical isolates of ceftazidime resistant Pseudomonas Aeruginosa.

We studied the prevalence of ceftazidime resistance in Pseudomonas aeruginosa and the rates of extended-spectrum ß-lactamase (ESBL), AmpC ß-lactamase (AmpC) and metallo-ß-lactamase (MBL) production among the ceftazidime resistant Pseudomonas aeruginosa. A very high rate of MBL production was observed, which suggested it to be an important contributing factor for ceftazidime resistance among Pseudomonas aeruginosa.