Health care associated Clostridioides difficile infection and colonization in patients admitted at tertiary care hospital Pakistan.

Objectives: To evaluate the epidemiology of clostridioides difficile infections and colonisation in a tertiary-care setting. METHODS: The cross-sectional study was conducted at the Combined Military Hospital, Rawalpindi, Pakistan, from June 1, 2017, to October 31, 2019, and comprised adult patients admitted in high-risk units of the hospital for any disease experiencing watery stools after 48 hours of hospital admission and passing more than 3 stools per day with no other recognised aetiology. Stool samples of the participants, diagnosed with antibiotic associated diarrhoea, were submitted for glutamate dehydrogenase antigen assay and clostridioides toxin A/B assay detected by enzyme-linked immunosorbent assay and clostridioides difficile toxin gene detection by polymerase chain reaction. Clostridium difficile-associated diarrhoea was diagnosed by a positive toxin assay or polymerase chain reaction. Data was analysed using SPSS25. RESULTS: Of the 715 subjects, 322(45%) were males and 393(55%) were females. The overall mean age was 56.64±8.57 years, and 488(68.3%) were aged <60 years, while 227(31.7%) were aged >60 years. The incidence of clostridioides difficile-associated diarrhoea was found in 10(1.4%) patients and was highest in oncology unit 3(4.3%). No positive case was detected from the high dependency unit and the surgical ward. All the10(1.4%) positive cases were on >2 antibiotics with a combination of oral vancomycin and intravenous metronidazole. Mortality rate was significantly higher in the positive cases compared to those with clostridioides difficile colonisation (p<0.05). CONCLUSIONS: The incidence of clostridioides difficile-associated diarrhoea was found to be low.

Divergent synthesis and elaboration of structure activity relationship for quinoline derivatives as highly selective NTPDase inhibitor.

Quinoline derivatives have interesting biological profile. In continuation for the comprehensive evaluations of substituted quinoline derivatives against human nucleoside triphosphate diphosphohydrolases (h-NTPDases) a series of substituted quinoline derivatives (2a-g, 3a-f, 4, 5a-c, 6) was synthesized. The inhibitory activities of the synthesized compounds were evaluated against four isoenzymes of human nucleoside triphosphate diphosphohydrolases (h-NTPDases). These quinoline derivatives had IC50 (µM) values in the range of 0.20-1.75, 0.77-2.20, 0.36-5.50 and 0.90-1.82 for NTPDase1, NTPDase2, NTPDase3 and NTPDase8, respectively. The derivative 3f was the most active compound against NTPDase1 (IC50, 0.20 ± 0.02 µM) that also possessed selectivity towards NTPDase1. Similarly, derivative 3b (IC50, 0.77 ± 0.06), 2h (IC50, 0.36 ± 0.01) and 2c (IC50, 0.90 ± 0.08) displayed excellent activity corresponding to NTPDase2, NTPDase3 and NTPdase8. The compound 5c emerged as a selective inhibitor of NTPDase8. The most active compounds were then investigated to determine their mode of inhibition and finally binding interactions of the active compounds were analyzed through molecular docking studies. The obtained results strongly support the quinoline scaffold's potential as potent and selective NTPDase inhibitor.

Evaluation of galactomannan and beta-d-glucan assays for the diagnosis of invasive aspergillosis in clinically suspected cases.

OBJECTIVE: To assess the utility of galactomannan and beta-D-glucan assays in the diagnosis of invasive aspergillosis in clinically suspected cases, and to compare their diagnostic potential to determine whether a combination of the two may result in an early and specific diagnosis. METHODS: The descriptive cross-sectional case-control study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from April 1, 2017, to March 31, 2018, and comprised serum samples from clinically suspected invasive aspergillosis patients and healthy controls. The sera were tested for galactomannan and beta-D-glucan detection. Proven, probable and possible categories of invasive aspergillosis according to European Organisation for Research and Treatment of Cancer / Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria. Galactomannan antigen was detected using a one-stage immunoenzymatic sandwich microplate assay. Beta-D-Glucan antigen was detected using a protease zymogen-based colorimetric assay. Sensitivity and positive / negative likelihood ratio of both the cases and the controls were calculated and compared. RESULTS: Of the 178 subjects, 119(67%) were cases and 59(33%) were controls. Beta-D-glucan assay was more sensitive than galactomannan assay (91.6% versus 80.67%) whereas galactomannan assay was more specific than beta-D-glucan assay (86.44% versus 76.27%) in the diagnosis of invasive aspergillosis. The sensitivities of both assays decreased with decreasing probability of invasive aspergillosis, i.e., maximum sensitivities of both beta-D-glucan and galactomannan assays were for proven cases (100% versus 87.5%), followed by probable cases (89.29% versus 85.71%), and possible cases (91.57% versus 78.31%). CONCLUSIONS: Both beta-D-glucan and galactomannan assays seemed to play an encouraging role in the diagnosis of invasive aspergillosis in high-risk clinically suspected cases, with the former assay being more sensitive and the latter assay being more specific.

Linezolid-Resistant Methicillin-Resistant Staphylococcus HemolyticusIsolated from Leukemic Patient: First Case Report from Pakistan.

Methicillin-Resistant Coagulase-Negative Staphylococcusposes a challenging situation in healthcare settings. The spread of resistance among such organisms against major drugs is alarming as it limits the treatment options for serious infections. Traditionally, Vancomycin had remained a mainstay of treatment of Methicillin-Resistant Staphylococci. Linezolid introduction into the clinical practice was a major breakthrough since it provided orally administered treatment of Methicillin-Resistant Staphylococci. Widespread use of Linezolid has gradually turned the impending fear of emergence of resistance against this novel drug into a reality. We report first case of Linezolid-Resistant Methicillin-Resistant Staphylococcushemolyticusfrom Pakistan, isolated from a leukemic patient. The organism caused a necrotic lesion on the right forearm at cannulation site of intravenous catheter. Ooze swab yielded the pure growth of Linezolid-Resistant Methicillin-Resistant Staphylococcushemolyticus.

Dual Infection by Burkholderia Cepaciaand Pseudomonas Putida in an Infective Endocarditis Case.

Infective endocarditis is rarely caused by Burkholderia cepacia. Pseudomonas putidahas not been reported to cause infective endocarditis so far. This is the first case of infective endocarditis being reported, that is caused by Pseudomonas putidaand Burkholderia cepaciain an immunocompetent host with no predisposing factors. Aortic valve replacement surgery was carried out and antibiotics were given, to which the patient responded well and recovered.