Association ofβ-lactam antimicrobial's exposure with carbapenem-resistant Pseudomonas aeruginosa infection:a cumulative meta-analysis

Background:Carbapenems are effective against severe Pseudomonas aeruginosa nosocomial infections.Therefore,carbapenem-resistant Pseudomonas aeruginosa is a serious public health threat.An understanding of the risk of inappropriate exposure to different antimicrobials in resistant Pseudomonas aeruginosa infection could help in elucidating the effective approach towards using antimicrobials in vulnerable patients with CRPA infection.Object:To investigate the association between exposure ofβ-lactam antimicrobials and CRPA infection relative to control patients.Methods:The MEDLINE/PubMed and OVID/Embase databases were used to search case-control and cohort studies in English language which reported antimicrobial exposure as risk factors for CRPA infection.The pooled odds ratios(OR)were calculated using a random-effect and fixed-effect model,and forest plots from a cumulative meta-analysis method were used to better show how pooled OR changed as updated evidence accumulated.Results:A total of 24 studies comprising 7039 participants were included for cumulative meta-analysis.A positive correlation was found between development of CRPA infection and exposure of beta-lactam antimicrobials:carbapenems(OR=7.60,95%CI:3.95 to 14.62,P<0.0001),imipenem(OR=9.81,95%CI:5.56 to 17.33),ampicillin(OR=1.86,95%CI:1.14 to 2.41),piperacillin(OR=2.82,95%CI:1.46 to 2.43),penicillins(OR=1.42,95%CI:0.90 to 2.24),cephalosporins(OR=1.88,95%CI:1.46 to 2.43)andβlactamase inhibitors(OR=1.96,95%CI:1.44 to 2.67).Further,exposure of other antimicrobial agents like quinolone(OR=2.35,95%CI:1.78 to 3.10),ciprofloxacin(OR=2.35,95%CI:1.66 to 3.95),aminoglycoside(OR=2.17,95%CI:1.60 to 2.95),amikacin(OR=3.11,95%CI:2.10 to 4.61),glycopeptides(OR=3.02,95%CI:1.92 to 4.75)and vancomycin(OR=3.26,95%CI:1.48 to 7.18),were also found to be positively associated with development of CRPA infection.Conclusions:Exposure of all kinds ofβ-lactams is significantly associated with development of carbapenemresistant Pseudomonas aeruginosa infection.These findings provide an impetus to take a more active approach while usingβ-lactam antimicrobials in patients with resistant Pseudomonas aeruginosa infections.

Efficacy and safety of pharmacotherapeutic interventions used in visceral leishmaniasis clinical trials:A systematic review and network meta-analysis

Objective:To compare the efficacy and safety outcomes of different antileishmanial agents used in visceral leishmaniasis clinical trials.Methods:A systematic literature search in PubMed/MEDLINE,EMBASE,Cochrane,and Google Scholar was done using keywords“randomized controlled trials”,“antileishmanial”and“visceral leishmaniasis”.The outcomes included were cure rate,overall withdrawals,relapse rate,and treatment-emergent adverse events.Effect estimates through the frequentist network meta-analysis approach were presented as OR with 95%CI.Rankogram plots were used for identifying the“best intervention”based on p-scores obtained using the surface under the cumulative ranking.The risk of bias was evaluated by using Pedro Scale.Results:Seventeen randomized controlled trials with 5143 visceral leishmaniasis patients who received different antileishmanial agents(amphotericin B,miltefosine,paromomycin,meglumine antimoniate,sodium stibogluconate,sitamaquine,and pentavalent antimonials)and met the inclusion criteria were included.For efficacy outcomes of the treatments,the rankogram of the network meta-analysis revealed that paromomycin(p-score=0.8148)has the highest probability of being best in the pool,followed by sodium stibogluconate(OR 0.82,95%CI 0.24-2.79,p-score=0.7580),amphotericin B+miltefosine(OR 0.66,95%CI 0.02-19.04,p-score=0.7329)as compared to the remaining treatments;however,the most of the treatment-emergent adverse events were reported with sitamaquine.Conclusions:Paromomycin reported the highest cure rates,while the maximum treatment-emergent adverse events were seen with sitamaquine.

Non-alcoholic fatty liver disease development:A multifactorial pathogenic phenomena

Non-alcoholic fatty liver disease(NAFLD),characterized by the accumulation of excessive intrahepatic fat,is a leading metabolic disorder also considered as the hepatic manifestation of metabolic syndrome(MS).Though more commonly observed in obese individuals and those with metabolic risk factors,it also develops in a considerable number of non-obese individuals as well as participants without having any component of MS.The basic mechanism involved in the development of fatty liver is the imbalance between lipid uptake,synthesis,and metabolism in the liver,normally controlled by several mechanisms to maintain lipid homeostasis.As a complex progressive liver disorder,the NAFLD pathogenesis is multifactorial,and several new pathogenic phenomena were discovered over time.The available literature suggests the role of both genetic and environmental factors and associated metabolic factors;however,the mechanism of progression is not completely understood.In this review,we discuss different pathogenic mechanisms and their interplay to provide an elaborate idea regarding NAFLD development and progression.Better understanding of pathogenic mechanisms will be useful in finding new treatment for patients with NAFLD.