Early- vs Late-onset Ventilator-associated Pneumonia in Critically Ill Adults: Comparison of Risk Factors, Outcome, and Microbial Profile.

Background: Ventilator-associated pneumonia (VAP) is one of the most frequent hospital-acquired infections, which develops in mechanically ventilated patients after 48 hours of mechanical ventilation. The purpose of this study was to determine the incidence rate, various risk factors, microbiological profile, and outcome of early- vs late-onset ventilator-associated pneumonia (VAP) in medical intensive care unit (MICU). Materials and methods: This prospective study was conducted on 273 patients admitted to the MICU in JIPMER, Puducherry, from October 2018 to September 2019. Results: The incidence of VAP was 39.59 per 1000 ventilation days of MICU patients (93/273). Of these, 53 (56.9%) patients had early-onset VAP and 40 (43.1%) had late-onset VAP. Multiple logistic regression analysis showed that steroid therapy, supine head position, coma or impaired unconsciousness, tracheostomy, and re-intubation were found to be independent predictors of early- and late-onset VAP, respectively. Most cases of VAP were caused by Gram-negative bacteria (90.6%), with nonfermenters contributing to 61.8%. The most frequent pathogens causing early-onset VAP were Acinetobacter baumannii (28.9%) and Pseudomonas aeruginosa (20.6%), while in late-onset VAP, A. baumannii (32.9%) and Klebsiella pneumoniae (21.9%) were the most common. Maximum death rate was seen in patients infected with Escherichia coli (50%) and Stenotrophomonas maltophilia (38.5%). There was no significant association between the presence of VAP and mortality among the studied population. Conclusion: The incidence of VAP in our study was high. There were no significant differences in the prevalence of pathogens associated with early-onset or late-onset VAP. Our study shows that early-onset and late-onset VAP have different risk factors, highlighting the need for developing different preventive and therapeutic strategies. How to cite this article: Gunalan A, Sastry AS, Ramanathan V, Sistla S. Early- vs Late-onset Ventilator-associated Pneumonia in Critically Ill Adults: Comparison of Risk Factors, Outcome, and Microbial Profile. Indian J Crit Care Med 2023;27(6):411-415.

Concordance between the National Healthcare Safety Network (NHSN) Surveillance Criteria and Clinical Pulmonary Infection Score (CPIS) Criteria for Diagnosis of Ventilator-associated Pneumonia (VAP).

Background: Ventilator-associated pneumonia (VAP) is one of the most common hospital-acquired infections among mechanically ventilated patients and the incidence rates are widely used as an index of quality of care given in an ICU. Since there is no gold standard method available to diagnose VAP, the incidence rate varies based on different criteria used for calculation. Therefore, we conducted a study to determine the concordance between the National Healthcare Safety Network (NHSN) surveillance criteria and clinical pulmonary infection score (CPIS) criteria for the diagnosis of VAP. Materials and methods: This was a prospective study that evaluated patients in the medical intensive care units (MICUs) of a tertiary care hospital, India, who were intubated for >48 hours between October 2018 and September 2019. All the patients (n = 273) were followed up daily and assessed using both CPIS and NHSN surveillance criteria for diagnosing VAP. Results: Of these 273 patients, 93 patients (34.1%) had VAP according to CPIS criteria as compared with 33 patients (12.1%) using the NHSN criteria. The corresponding rates of VAP were 39.59 vs 11.53 cases per 1,000 ventilator days, respectively. The agreement of the two sets of criteria was fairly good (kappa statistics, 0.42) Conclusion: The NHSN surveillance criteria have a lower sensitivity in detecting VAP cases and have to be modified to achieve better results. How to cite this article: Gunalan A, Sistla S, Sastry AS, Venkateswaran R. Concordance between the National Healthcare Safety Network (NHSN) Surveillance Criteria and Clinical Pulmonary Infection Score (CPIS) Criteria for Diagnosis of Ventilator-associated Pneumonia (VAP). Indian J Crit Care Med 2021;25(3):296-298.

Detection of heterogeneous vancomycin-intermediate Staphylococcus aureus: A preliminary report from south India.

Background & objectives: Although there are reports of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) across the globe, there is a lack of reliable data on hVISA in India. The present study was undertaken to determine the rate of hVISA among the methicillin-resistant Staphylococcus aureus (MRSA) isolates, and to compare the brain heart infusion agar with vancomycin 4 µg/ml (BHIV4) method with population analysis profile-area under the curve (PAP-AUC) method for the detection of hVISA and to study the distribution of mobile genetic element that carries methicillin-resistance gene SCCmec (Staphylococcal cassette chromosome mec) types among these isolates. Methods: BHIV4 and PAP-AUC methods were employed to detect hVISA among 500 clinical isolates of MRSA. SCCmec typing of these isolates was performed by multiplex polymerase chain reaction. The clinical presentation, treatment with vancomycin and outcome was documented for patients with hVISA. Results: The rate of hVISA was 12.4 per cent by PAP-AUC method. Sensitivity, specificity, PPV, NPV and kappa agreement of BHIV4 with PAP-AUC was 58.06, 93.15, 54.55, 94.01 per cent and 0.498, respectively. The isolation of hVISA was significantly (P<0.01) higher in patients admitted to intensive care units and wards than in patients attending the outpatient departments. Only 38 per cent of the patients received vancomycin as therapy. Majority of the hVISA isolates carried SCCmec type V or IV. Interpretation & conclusions: The rate of hVISA isolation in our study was 12.4 per cent. The sensitivity of the BHIV4 screening test was low, and was in moderate agreement with PAP-AUC test. SCCmec type V was the predominant type seen in half of the isolates. More studies need to be done in different parts of the country on a large number of isolates to confirm our findings.

Establishing Antimicrobial Resistance Surveillance & Research Network in India: Journey so far.

The Indian Council of Medical Research, in 2013, initiated the Antimicrobial Resistance Surveillance & Research Network (AMRSN) to enable compilation of data on six pathogenic groups on antimicrobial resistance from the country. The overarching aim of this network was to understand the extent and pattern of antimicrobial resistance (AMR) and use this evidence to guide strategies to control the spread of AMR. This article describes the conception and implementation of this AMR surveillance network for India. Also described are the challenges, limitations and benefits of this approach. Data from the Network have shown increasing resistance in Gram-negative bacteria in the hospitals that are part of this network. Combined resistance to third-generation cephalosporins and fluoroquinolones and increasing carbapenem resistance are worrisome, as it has an important bearing on the patients' outcome and thus needs to be addressed urgently. Data generated through this Network have been used to develop treatment guidelines, which will be supportive in harmonizing treatment practices across the tertiary level healthcare institutions in the country. While, the major benefit of having a surveillance system is the collection of real-time accurate data on AMR including the mechanisms of resistance, representativeness to community, sustaining the current effort and expanding the current activities to next levels of healthcare settings are the major challenges. The data emanating from the network besides providing evidence, expose several gaps and lacunae in the ecosystem and highlight opportunities for action by multiple stakeholders.

Molecular characterization of extended-spectrum ß-lactamases among clinical isolates of Escherichia coli & Klebsiella pneumoniae: A multi-centric study from tertiary care hospitals in India.

Background & objectives: The increasing prevalence of extended-spectrum ß-lactamases (ESBLs) has abated therapeutic options worldwide. This study was undertaken to investigate the molecular profile and resistance patterns of ESBLs among clinical isolates of Escherichia coli and Klebsiella pneumoniae at four tertiary care centres in India. Methods: Clinical isolates of E. coli and K. pneumoniae were collected from the All India Institute of Medical Sciences (AIIMS), New Delhi; the Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry; Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh and Christian Medical College (CMC), Vellore, over one and a half year period. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion method. ESBLs were confirmed phenotypically, and multiplex PCR was performed to identify genes for ß-lactamases (blaTEM, blaSHV, blaOXA-1, blaCTXM-1, blaCTXM-2, blaCTXM-9 and blaCTXM-15). Results: Among 341 E. coli isolates collected during the study period, 171 (50%) harboured blaTEM, 145 (43%) blaOXA-1,70 (21%) blaCTXM-1, 19 (6%) blaSHV and four (1%) harboured blaCTXM-2. Phenotypically, combined disc test detected ESBL production in 98/298 (33%) E. coli. Among 304 K. pneumoniae isolates, 115 (38%), 89 (29%), 83 (27%), 64 (21%) and two (0.6%) harboured blaTEM, blaOXA-1, blaCTXM-1, blaSHV and blaCTXM-2, respectively. Combined disc test (CDT) detected ESBL production in 42 per cent K. pneumoniae. Most of the blaCTXM-1positive isolates were also blaCTXM-15 positive. The carbapenem susceptibility ranged from 56 to 88 per cent for E. coli and from 20 to 61 per cent for K. pneumoniae. Antibiotic sensitivity patterns showed that colistin (CST) was the most sensitive drug for both E. coli (271/274, 99%) and K. pneumoniae (229/234, 98%). Interpretation & conclusions: The prevalence of ESBL among four study centres varied, and blaTEM, blaOXA-1 and blaCTXM-15 were the most common genotypes in E. coli and K. pneumoniae isolates in India. The growing carbapenem resistance and emerging colistin resistance warrant the judicious use of these antimicrobials.

Molecular characterization & epidemiology of carbapenem-resistant Acinetobacter baumannii collected across India.

Background & objectives: Acinetobacter baumannii is an opportunistic pathogen responsible for causing nosocomial infections. A. baumannii develops resistance to various antimicrobial agents including carbapenems, thereby complicating the treatment. This study was performed to characterize the isolates for the presence of various ß-lactamases encoding genes and to type the isolates to compare our clones with the existing international clones across five centres in India. Methods: A total 75 non-repetitive clinical isolates of A. baumannii from five different centres were included in this study. All the isolates were confirmed as A. baumannii by bl aOXA-51-likePCR. Multiplex PCR was performed to identify the presence of extended spectrum ß-lactamases (ESBL) and carbapenemases. Multilocus sequence typing was performed to find the sequence type (ST) of the isolates. e-BURST analysis was done to assign each ST into respective clonal complex. Results: blaOXA-51-likewas present in all the 75 isolates. The predominant Class D carbapenemase was blaOXA-23-likefollowed by Class B carbapenemase, blaNDM-like. Class A carbapenemase was not observed. blaPER-likewas the predominant extended spectrum ß-lactamase. ST-848, ST-451 and ST-195 were the most common STs. Eight-novel STs were identified. e-BURST analysis showed that the 75 A. baumannii isolates were clustered into seven clonal complexes and four singletons, of which, clonal complex 208 was the largest. Interpretation & conclusions: Most of the isolates were grouped under clonal complex 208 which belongs to the international clonal lineage 2. High occurrence of ST-848 carrying blaOXA-23-likegene suggested that ST-848 could be an emerging lineage spreading carbapenem resistance in India.

Rare isolation of Fusobacterium varium from a case of Fournier's gangrene.

Fusobacterium is a gram negative obligate anaerobic bacilli, a normal inhabitant of gastrointestinal tract, oropharynx and female genital tract. Here we report a case of Fourniers gangrene from which Fusobacterium varium has been isolated along with certain other pathogens. There are only a few reported cases of Fusobacterium varium in literature and it has never been reported from Fournier's gangrene. Through this report we intend to shed some light on the pathogenic potential of anaerobes which are considered as normal flora.

Brain abscess and cervical lymphadenitis due to Paraclostridium bifermentans: A report of two cases.

Paraclostridium bifermentans (current nomenclature of Clostridium bifermentans since 2016) is a gram-positive, spore-forming anaerobic bacterium. Here, we describe two cases associated with this organism. The first, primarily a case of tubercular brain abscess where P. bifermentans was isolated as part of a polymicrobial flora, following a neurosurgical procedure for the same and the second, a case of cervical lymphadenitis from which it was isolated as the sole causative agent. There are only a few reported cases of P. bifermentans in literature and these cases illustrate the widening spectrum of infections related to it.

Effect of disease-modifying antirheumatic drug therapy on immune response to trivalent influenza vaccine in rheumatoid arthritis.

BACKGROUND & OBJECTIVES: Patients with autoimmune rheumatic diseases may be at an increased risk of infection due to disease and use of disease-modifying antirheumatic drug (DMARD) therapy. The present study was done to evaluate the immune response to influenza vaccination in patients with rheumatoid arthritis (RA). METHODS: Fifty one RA patients on stable methotrexate (MTX) therapy (≥15 mg/wk), 51 newly diagnosed DMARD-naïve RA patients and 45 healthy controls received a single dose of inactivated seasonal trivalent influenza vaccine. Blood samples were collected just prior to and four weeks after vaccination. Pre- and post-vaccination antibody titres against the three virus strains were measured by hemagglutination inhibition assay. The impact of age, gender, DMARD treatment and pre-vaccination seroprotection on response to the vaccine was assessed by binary logistic regression analysis for each of the virus strains. RESULTS: Pre-vaccination antibody titres were found to be high in the three study groups for all influenza strains, except for Yamagata strain, the titres for which were low in healthy controls. Trivalent influenza vaccination was found to be safe and stimulated a good antibody response in all study groups. On regression analysis, there was no association of age, gender or MTX therapy with vaccine response, except for Yamagata strain where healthy controls had higher positive immune response (P=0.008; odds ratio - 3.37, 95% confidence interval: 1.36-8.32). INTERPRETATION & CONCLUSIONS: Our results indicated that influenza vaccination was safe in RA patients with no detrimental effect on disease activity. MTX therapy at a dose ≥15 mg/wk did not affect the vaccine response. Presence of high pre-vaccination seroprotective antibody levels in the study population indicates the need for re-examination of recommended annual influenza vaccination in such subgroups of population.

A case of pyometrocolpos with Bifidobacterium species.

Bifidobacterium species, a normal commensal of the human gastrointestinal tract, female genitourinary tract and vagina is usually considered non-pathogenic and is being used therapeutically as probiotic due to its beneficial effects. However, there are several case reports implicating Bifidobacteria as the causative agent in various infectious conditions. Infections with Bifidobacteria are often ignored or underreported as they are part of the normal gut microbiome. Here we discuss a case of pyometrocolpos with Bifidobacterium species. Clinical outcome of the patient was good after emergency drainage and antibiotic treatment with Cefoperazone sulbactam and Metronidazole.

Clostridium perfringens - A bacterial pathogen gaining recognition in necrotizing pancreatitis.

We report an interesting case of necrotizing pancreatitis due to Clostridium perfringens in an elderly man who came to the hospital with complaints of severe abdominal pain. The infection further worsened with the dissemination to other internal organs. The patient did not show any improvement despite intensive care and treatment. This emphasizies the fact that early diagnosis and appropriate treatment would reduce the morbidity associated with necrotizing pancreatitis.

Evaluation of colorimetric nitrate reductase assay for rapid detection of methicillin resistance in clinical isolates of Staphylococcus aureus.

BACKGROUND & OBJECTIVES: Methicillin resistant Staphylococcus aureus (MRSA) remains a major cause of health care-associated infections. Rapid detection of MRSA facilitates the early initiation of appropriate treatment and infection control. Hence, the present study was undertaken to standardize and evaluate the performance of rapid colorimetric nitrate reductase assay (NRA) for determining methicillin resistance in S.aureus. METHODS: A total of 160 clinical isolates of S. aureus, (80 each of methicillin susceptible and methicillin resistant) were included in the study. Minimum inhibitory concentration (MIC) was determined by NRA and reference broth micro dilution (BMD) methods. Results of NRA were compared with BMD and analyzed. RESULTS: For MRSA, the MIC values ranged from 4 to ≥ 16 µg/ml and for MSSA, ≤ 0.5 to 2 µg/ml. Category and essential agreement for NRA as compared with BMD were found to be 99.4 and 89.7 per cent, respectively. No minor or major discrepancy was observed. A single resistant isolate showed very major discrepancy. INTERPRETATION & CONCLUSIONS: Colorimetric NRA being an inexpensive test requiring no special equipment can be employed as an alternative method for rapid detection of MRSA in resource limited settings.

Utility of quantitative loop mediated isothermal amplification (qLAMP) assay for the diagnosis of invasive pneumococcal disease (IPD).

PURPOSE: Quantitative LAMP (qLAMP) assay is one of the recent and emerging diagnostic tests for infectious diseases. Only a few studies exist comparing this assay with quantitative real-time PCR (qPCR) for the diagnosis of invasive pneumococcal disease (IPD). AIM: To compare the diagnostic performance of qLAMP assay with qPCR targeting autolysin gene for the diagnosis of invasive pneumococcal disease. METHODS: Ninety six blood samples and 73 CSF samples from patients clinically suspected with community acquired pneumonia and acute meningitis were tested by qPCR and qLAMP assays using previously published primers and protocols. The qPCR was considered as the gold standard test and the diagnostic performance was assessed by calculating sensitivity, specificity, positive and negative predictive values, and kappa coefficient for the level of agreement between the tests. Chi-squared/Fisher exact test was used to compare categorical variables (positive/negative). RESULTS: Thirty two blood samples and 22 CSF samples were positive by qPCR while 24 and 20 samples were positive by qLAMP assay respectively. The sensitivity of qLAMP assay was only 86.4% and 75% when tested on CSF and blood samples respectively. However, the qLAMP assay was in substantial to almost perfect agreement when compared with qPCR. The results were statistically significant in both sample types (P < 0.001). CONCLUSIONS: The performance of qLAMP assay can vary based on the specimen type. It has very high specificity and had substantial to almost perfect agreement, and thus may be an alternative to qPCR for the diagnosis of IPD.

Evaluation of different linezolid susceptibility testing methods and detection of linezolid resistance gene (cfr) in staphylococcal isolates.

Linezolid is an effective oxazolidinone antibiotic against multi resistant Gram-positive organisms. Linezolid resistance is an emerging problem and some controversy exists about the reliability of different phenotypic methods of linezolid susceptibility testing. Fifty isolates each of methicillin resistant S. aureus (MRSA) and Staphylococcus haemolyticus were tested for linezolid susceptibility using Kirby-Bauer disc diffusion, E-test, automated system VITEK2, Broth micro-dilution (reference method) and PCR for the cfr gene. Six resistant isolates were identified, three each in MRSA and S. haemolyticus, all carrying the cfr gene. E-test and VITEK2 were found to be more accurate than disc diffusion test.

Species distribution and antimicrobial susceptibility of Burkholderia cepacia complex isolates in clinical infections: Experience from a tertiary care hospital, Southern India.

PURPOSE: Burkholderia cepacia complex (Bcc) is a diverse group of environmental bacteria associated with opportunistic infections. The identification of Bcc using conventional methods poses challenges. Bcc infections are difficult to treat due to intrinsic antibiotic resistance. The study aimed to investigate the species distribution and antimicrobial susceptibility of clinical Bcc isolates. METHODS: A total of 153 Bcc isolates obtained from clinical samples were analysed. Species identification was carried out using automated methods, including MALDI-TOF MS and VITEK2. Antimicrobial susceptibility testing was performed using the disc diffusion method. RESULTS: Burkholderia cenocepacia (70.5%) emerged as the most prevalent species, followed by Burkholderia contaminans (9.8%) and Burkholderia cepacia (7.2%). Ventilator-associated pneumonia (38.6%) was the most common infection, followed by sepsis (28.1%). Co-existence of Bcc with other pathogens in many cases suggested potential co-infection scenarios. Antimicrobial susceptibility revealed that ceftazidime, co-trimoxazole and meropenem were the most effective drugs, while levofloxacin proved to be the least effective. Moderate susceptibility was noted to minocycline, with 4.6% of isolates exhibiting multi-drug resistance. CONCLUSION: This study provides valuable insights into the prevalence, clinical associations, and antibiotic susceptibility of Bcc in India. It highlights the importance of Bcc as a nosocomial pathogen, especially in vulnerable patient populations. The findings contribute to understanding Bcc infections, their distribution, and emphasize the necessity for accurate identification methods in clinical settings.

Outbreak of Burkholderia cenocepacia in an intensive care unit of a tertiary care hospital identified by pulsed-field gel electrophoresis.

Nosocomial outbreaks of Burkholderia cepacia complex, transmitted through contaminated medical surfaces or equipment have been reported. Pulsed-field Gel Electrophoresis (PFGE) is recognized as the "gold standard" for molecular subtyping, yet studies on clonal relationships in India are limited. PFGE was used to study the clonal relationships of 22 isolates of Burkholderia cenocepacia from 12 patients admitted to a critical care unit during 2 months (November and December 2021). PFGE revealed three different profiles with 15 isolates belonging to a single cluster suggesting a common source within the hospital, emphasizing the need for preventive measures to control B. cenocepacia transmission.

Influence of COVID-19 over seasonal influenza activity in southern India.

Basic epidemiological data is urgently needed in order to ascertain the changes brought about by COVID-19 pandemic, and help researchers, clinicians, and policy makers in addressing these issues. Data on influenza positivity from 2009 to 2019 was collected from Regional Influenza laboratory, JIPMER. Being COVID testing centre we tested samples (2020-2023) from Tamilnadu and Pondicherry. All SARI samples which were negative for COVID-19 were subjected to Influenza testing as regular surveillance activity was suspended. On comparison we found significant reduction in detection rates of influenza A H1N1, H3N2 and influenza B (p value = <0.01).