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 of β-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 stud-ies 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 cumula-tive meta-analysis method were used to better show how pooled OR changed as updated evidence accumulated.Results:A total of 24 studies comprising 7 039 participants were included for cumulative meta-analysis.A posi-tive 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),ampi-cillin(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)and β lactamase 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 infec-tion.Conclusions:Exposure of all kinds of β-lactams is significantly associated with development of carbapenem-resistant Pseudomonas aeruginosa infection.These findings provide an impetus to take a more active approach while using β-lactam antimicrobials in patients with resistant Pseudomonas aeruginosa infections.

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 5 143 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=0.814 8) 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=0.758 0), amphotericin B+miltefosine (OR 0.66, 95% CI 0.02-19.04, p-score=0.732 9) 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.