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Clinical Microbiology and Infection :... May 2024The optimal empiric antibiotic regimen for non-ventilator-associated hospital-acquired pneumonia (HAP) is uncertain. (Review)
Review
Empiric antibiotic regimens in adults with non-ventilator-associated hospital-acquired pneumonia: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
The optimal empiric antibiotic regimen for non-ventilator-associated hospital-acquired pneumonia (HAP) is uncertain.
OBJECTIVES
To compare the effectiveness and safety of alternative empiric antibiotic regimens in HAP using a network meta-analysis.
DATA SOURCES
Medline, EMBASE, Cochrane CENTRAL, Web of Science, and CINAHL from database inception to July 06, 2023.
STUDY ELIGIBILITY CRITERIA
RCTs.
PARTICIPANTS
Adults with clinical suspicion of HAP.
INTERVENTIONS
Any empiric antibiotic regimen vs. another, placebo, or no treatment.
ASSESSMENT OF RISK OF BIAS
Paired reviewers independently assessed risk of bias using a modified Cochrane tool for assessing risk of bias in randomized trials.
METHODS OF DATA SYNTHESIS
Paired reviewers independently extracted data on trial and patient characteristics, antibiotic regimens, and outcomes of interest. We conducted frequentist random-effects network meta-analyses for treatment failure and all-cause mortality and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.
RESULTS
Thirty-nine RCTs proved eligible. Thirty RCTs involving 4807 participants found low certainty evidence that piperacillin-tazobactam (RR compared to all cephalosporins: 0.65; 95% CI: 0.42, 1.01) and carbapenems (RR compared to all cephalosporins: 0.77; 95% CI: 0.53, 1.11) might be among the most effective in reducing treatment failure. The findings were robust to the secondary analysis comparing piperacillin-tazobactam vs. antipseudomonal cephalosporins or antipseudomonal carbapenems vs. antipseudomonal cephalosporins. Eleven RCTs involving 2531 participants found low certainty evidence that ceftazidime and linezolid combination may not be convincingly different from cephalosporin alone in reducing all-cause mortality. Evidence on other antibiotic regimens is very uncertain. Data on other patient-important outcomes including adverse events was sparse, and we did not perform network or pairwise meta-analysis.
CONCLUSIONS
For empiric antibiotic therapy of adults with HAP, piperacillin-tazobactam might be among the most effective in reducing treatment failure. Empiric methicillin-resistant Staphylococcus aureus coverage may not exert additional benefit in reducing mortality.
REGISTRATION
PROSPERO (CRD 42022297224).
PubMed: 38823453
DOI: 10.1016/j.cmi.2024.05.017 -
Frontiers in Medicine 2022Eravacycline is a novel, fully synthetic fluorocycline antibiotic for the treatment of adults with complicated intra-abdominal infections (cIAIs). However, the efficacy...
The efficacy and safety of eravacycline compared with current clinically common antibiotics in the treatment of adults with complicated intra-abdominal infections: A Bayesian network meta-analysis.
BACKGROUND
Eravacycline is a novel, fully synthetic fluorocycline antibiotic for the treatment of adults with complicated intra-abdominal infections (cIAIs). However, the efficacy and safety of eravacycline compared with current clinically common antibiotics remain unknown.
OBJECTIVE
This study aims to compare the efficacy and safety of eravacycline and other clinically common antibiotics in China, including tigecycline, meropenem, ertapenem, ceftazidime/avibactam+metronidazole, piperacillin/tazobactam, imipenem/cilastatin, and ceftriaxone+metronidazole, for the treatment of adults with cIAIs and to provide a reference for clinical choice.
METHODS
The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were electronically searched to collect clinical randomized controlled studies (RCTs) comparing different antibiotics in the treatment of patients with cIAIs from inception to June 1, 2021. Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies.
RESULTS
A total of 4050 articles were initially retrieved, and 25 RCTs were included after screening, involving eight treatment therapies and 9372 patients. The results of network meta-analysis showed that in the intention-to-treat (ITT) population, the clinically evaluable (CE) population, and the microbiologically evaluable (ME) population, the clinical response rate of eravacycline was not significantly different from that of the other 7 therapies ( > 0.05). In terms of microbiological response rate, eravacycline was significantly better than tigecycline [tigecycline vs. eravacycline: RR = 0.82, 95%CI (0.65,0.99)], and there was no significant difference between the other 6 regimens and eravacycline ( > 0.05). In terms of safety, the incidence of serious adverse events, discontinuation rate, and all-cause mortality of eravacycline were not significantly different from those of the other 7 treatment therapies ( > 0.05).
CONCLUSION
Based on the evidence generated by the current noninferiority clinical trial design, the efficacy and safety of eravacycline for the treatment of adults with cIAIs are not significantly different from those of the other 7 commonly used clinical antibiotics in China. In terms of microbiological response rate, eravacycline was significantly better than tigecycline. In view of the severe multidrug-resistant situation in China, existing drugs have difficulty meeting the needs of clinical treatment, and the new antibacterial drug eravacycline may be one of the preferred options for the treatment of cIAIs in adults.
PubMed: 36186801
DOI: 10.3389/fmed.2022.935343 -
Antibiotics (Basel, Switzerland) Dec 2023Burn injury causes profound pathophysiological changes in the pharmacokinetic/pharmacodynamic (PK/PD) properties of antibiotics. Infections are among the principal... (Review)
Review
BACKGROUND
Burn injury causes profound pathophysiological changes in the pharmacokinetic/pharmacodynamic (PK/PD) properties of antibiotics. Infections are among the principal complications after burn injuries, and broad-spectrum beta-lactams are the cornerstone of treatment. The aim of this study was to review the evidence for the best regimens of these antibiotics in the burn patient population.
METHODS
We performed a systematic review of evidence available on MEDLINE (from its inception to 2023) of pharmacology studies that focused on the use of 13 broad-spectrum beta-lactams in burn patients. We extracted and synthetized data on drug regimens and their ability to attain adequate PK/PD targets.
RESULTS
We selected 35 studies for analysis. Overall, studies showed that both high doses and the continuous infusion (CI) of broad-spectrum beta-lactams were needed to achieve internationally-recognized PK/PD targets, ideally with therapeutic drug monitoring guidance. The most extensive evidence concerned meropenem, but similar conclusions could be drawn about piperacillin-tazobactam, ceftazidime, cefepime, imipenem-clinastatin and aztreonam. Insufficient data were available about new beta-lactam-beta-lactamase inhibitor combinations, ceftaroline, ceftobiprole and cefiderocol.
CONCLUSIONS
Both high doses and CI of broad-spectrum beta-lactams are needed when treating burn patients due to the peculiar changes in the PK/PD of antibiotics in this population. Further studies are needed, particularly about newer antibiotics.
PubMed: 38136771
DOI: 10.3390/antibiotics12121737 -
Open Forum Infectious Diseases Apr 2021In hospital settings, restriction of selected classes of antibiotics is usually believed to contribute to containment of resistance development. We performed a...
BACKGROUND
In hospital settings, restriction of selected classes of antibiotics is usually believed to contribute to containment of resistance development. We performed a systematic review and meta-analysis to assess the effect of restricting the use of specific antibiotic classes on the prevalence of resistant bacterial pathogens.
METHODS
We conducted a systematic literature search in Embase and PubMed/OVID MEDLINE. We included studies until June 4, 2020 in which a restrictive antibiotic policy was applied and prevalence of resistance and use of antibiotics were reported. We calculated the overall effect of antimicrobial resistance between postintervention versus preintervention periods using pooled odds ratios (ORs) from a mixed-effects model. We stratified meta-analysis by antibiotic-pathogen combinations. We assessed heterogeneity between studies using the I statistic and sources of heterogeneity using meta-regression.
RESULTS
We included 15 individual studies with an overall low quality of evidence. In meta-analysis, significant reductions in resistance were only observed with nonfermenters after restricting fluoroquinolones (OR = 0.77, 95% confidence interval [CI] = 0.62-0.97) and piperacillin-tazobactam (OR = 0.81, 95% CI = 0.72-0.92). High degrees of heterogeneity were observed with studies restricting carbapenem (Enterobacterales, I = 70.8%; nonfermenters, I = 81.9%), third-generation cephalosporins (nonfermenters, I = 63.3%), and fluoroquiolones (nonfermenters, I = 64.0%). Results were comparable when excluding studies with fewer than 50 bacteria. There was no evidence of publication bias for any of the antibiotic-pathogen combinations.
CONCLUSIONS
We could not confirm that restricting carbapenems or third-generation cephalosporins leads to decrease in prevalence of antibiotic resistance among Enterobacterales, nonfermenters, or Gram-positive bacteria in hospitalized patients. Nevertheless, reducing fluoroquinolone and piperacilline-tazobactam use may decrease resistance in nonfermenters.
PubMed: 33880388
DOI: 10.1093/ofid/ofab070 -
Antimicrobial Agents and Chemotherapy Sep 2019Concomitant use of vancomycin plus piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this...
Concomitant use of vancomycin plus piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this systematic review and meta-analysis, we searched PubMed and EMBASE for pediatric studies examining this hypothesis, with reference to vancomycin monotherapy or in combination with another beta-lactam antibiotic. Out of 1381 non-duplicate studies, 10 met our inclusion criteria. We performed a random effects meta-analysis, based on crude odds ratios, and we accounted for both quality of included studies and publication bias. In primary analysis, concomitant vancomycin and TZP use yielded a statistically significant association with the development of AKI. More specifically, children with AKI had higher odds to have been exposed to vancomycin plus TZP, in comparison with vancomycin monotherapy (OR 8.15; 95% CI: 3.49-18.99), or vancomycin plus any other beta-lactam antibiotic (OR 3.48; 95% CI: 2.71-4.46). Based on the results of the Newcastle Ottawa Scale quality assessment, a secondary analysis including only higher quality studies (6 out of 10 studies) yielded again higher odds of exposure to vancomycin plus TZP, compared to vancomycin plus another beta-lactam antibiotic (OR 3.76; 95% CI: 2.56-5.51). Notably, even after controlling for possible publication bias our results remained statistically significant (OR 3.09; 95% CI: 2.30-4.14). In conclusion, the concomitant use of vancomycin and TZP could be associated with AKI development and the clinical significance of this potential association needs to be studied further in the pediatric population.
PubMed: 31591125
DOI: 10.1128/AAC.01572-19 -
Frontiers in Public Health 2023(), a Gram-positive anaerobic bacterium, exhibits colonization tendencies on oral mucosal and skin surfaces, potentially evolving into a pathogenic entity associated... (Review)
Review
BACKGROUND
(), a Gram-positive anaerobic bacterium, exhibits colonization tendencies on oral mucosal and skin surfaces, potentially evolving into a pathogenic entity associated with diverse diseases. The diagnostic trajectory for -related diseases encounters delays, often with severe consequences, including fatality, attributed to the absence of symptom specificity and challenges in culture. The absence of a consensus on the diagnostic and therapeutic approaches to exacerbates the complexity of addressing associated conditions. This study aims to elucidate and scrutinize the clinical manifestations linked to , drawing insights from an extensive literature review of pertinent case reports.
CASE PRESENTATION
A 53-year-old male sought medical attention at our institution presenting with recurrent hemoptysis. Empirical treatment was initiated while awaiting pathogen culture results; however, the patient's symptoms persisted. Subsequent metagenomic next-generation sequencing (mNGS) analysis revealed a pulmonary infection attributable to . Resolution of symptoms occurred following treatment with piperacillin sulbactam sodium and moxifloxacin hydrochloride. A comprehensive literature review, utilizing the PubMed database, was conducted to assess case reports over the last decade where was identified as the causative agent.
CONCLUSION
The literature analysis underscores the predilection of for immunocompromised populations afflicted by cardiovascular diseases, diabetes, orthopedic conditions, and tumors. Risk factors, including oral and periodontal hygiene, smoking, and alcohol consumption, were found to be associated with infections. Clinical manifestations encompassed fever, cough, sputum production, and back pain, potentially leading to severe outcomes such as Spondylodiscitis, septic arthritis, lung abscess, bacteremia, sepsis, and mortality. While conventional bacterial culture remains the primary diagnostic tool, emerging technologies like mNGS offer alternative considerations. In terms of treatment modalities, β-lactam antibiotics and nitroimidazoles predominated, exhibiting recovery rates of 56.10% (46/82) and 23.17% (19/82), respectively. This case report and literature review collectively aim to enhance awareness among clinicians and laboratory medicine professionals regarding the intricacies of -associated infections.
Topics: Humans; Male; Middle Aged; Base Composition; Firmicutes; Hemoptysis; Phylogeny; Piperacillin; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Gram-Positive Bacterial Infections
PubMed: 38389952
DOI: 10.3389/fpubh.2023.1307902 -
Frontiers in Pediatrics 2020This study aimed to identify alterations in pharmacokinetics in children on extracorporeal membrane oxygenation (ECMO), identify knowledge gaps, and inform future...
This study aimed to identify alterations in pharmacokinetics in children on extracorporeal membrane oxygenation (ECMO), identify knowledge gaps, and inform future pharmacology studies. We systematically searched the databases MEDLINE, CINAHL, and Embase from earliest publication until November 2018 using a controlled vocabulary and keywords related to "ECMO" and "pharmacokinetics," "pharmacology," "drug disposition," "dosing," and "pediatrics." Inclusion criteria were as follows: study population aged <18 years, supported on ECMO for any indications, received any medications while on ECMO, and reported pharmacokinetic data. Clearance and/or volume of distribution values were extracted from included studies. Forty-one studies (total patients = 574) evaluating 23 drugs met the inclusion criteria. The most common drugs studied were antimicrobials ( = 13) and anticonvulsants ( = 3). Twenty-eight studies (68%) were conducted in children <1 year of age. Thirty-three studies (80%) were conducted without intra-study comparisons to non-ECMO controls. Increase in volume of distribution attributable to ECMO was demonstrated for nine (56%) drugs: cefotaxime, gentamicin, piperacillin/tazobactam, fluconazole, micafungin, levetiracetam, clonidine, midazolam, and sildenafil (range: 23-345% increase relative to non-ECMO controls), which may suggest the need for higher initial dosing. Decreased volume of distribution was reported for two drugs: acyclovir and ribavirin (50 and 69%, respectively). Decreased clearance was reported for gentamicin, ticarcillin/clavulanate, bumetanide, and ranitidine (range: 26-95% decrease relative to non-ECMO controls). Increased clearance was reported for caspofungin, micafungin, clonidine, midazolam, morphine, and sildenafil (range: 25-455% increase relative to non-ECMO controls). There were substantial pharmacokinetic alterations in 70% of drugs studied in children on ECMO. However, studies evaluating pharmacokinetic changes of many drug classes and those that allow direct comparisons between ECMO and non-ECMO patients are still lacking. Systematic evaluations of pharmacokinetic alterations of drugs on ECMO that incorporate multidrug opportunistic trials, physiologically based pharmacokinetic modeling, and other methods are necessary for definitive dose recommendations. : CRD42019114881.
PubMed: 32670992
DOI: 10.3389/fped.2020.00260 -
Antibiotics (Basel, Switzerland) Apr 2022The study aims to comparatively assess the nephrotoxicity of vancomycin when combined with piperacillin-tazobactam (V + PT) or meropenem (V + M) in adult patients...
Comparative Risk of Acute Kidney Injury Following Concurrent Administration of Vancomycin with Piperacillin/Tazobactam or Meropenem: A Systematic Review and Meta-Analysis of Observational Studies.
The study aims to comparatively assess the nephrotoxicity of vancomycin when combined with piperacillin-tazobactam (V + PT) or meropenem (V + M) in adult patients hospitalized in general wards or intensive care units. We searched MEDLINE, Google Scholar, and Web of Science for observational studies evaluating incidences of AKI in adult patients receiving V + PT or V + M for at least 48 h in general wards or intensive care units. The primary outcome was AKI events, while the secondary outcomes were hospital length of stay, need for renal replacement therapy (RRT), and mortality events. The odds ratio (OR), or mean difference for the hospital length of stay, with a corresponding 95% confidence interval (CI) from the inverse variance weighting random-effects model were estimated for the risk of AKI, RRT, and mortality. Of the 112 studies identified, twelve observational studies were included in this meta-analysis with a total of 14,511 patients. The odds of having AKI were significantly higher in patients receiving V + PT compared with V + M (OR = 2.31; 95%CI 1.69-3.15). There were no differences between V + PT and V + M in the hospital length of stay, RRT, or mortality outcomes. Thus, clinicians should be vigilant while using V + PT, especially in patients who are at high risk of AKI.
PubMed: 35453276
DOI: 10.3390/antibiotics11040526 -
Frontiers in Veterinary Science 2024Antibiotic resistance in represents a significant global public health concern. Among various serovars, enterica serovar Typhimurium is prevalent in multiple...
OBJECTIVE
Antibiotic resistance in represents a significant global public health concern. Among various serovars, enterica serovar Typhimurium is prevalent in multiple countries. This study aims to conduct a systematic review and meta-analysis to evaluate the pattern of antibiotic resistance in . Typhimurium isolates from diverse sources in Iran.
METHODS
We conducted a comprehensive and systematic search for relevant articles until December 2023 in the following databases: PubMed, Scopus, Web of Science, and SID. The collected data were analyzed using Stata software version 17.
RESULTS
Eighteen studies examined the pattern of antibiotic resistance in . Typhimurium for various antibiotics in Iran. Piperacillin and tetracycline exhibited the highest resistance rates, at 79 and 60% respectively, while cefixime and ceftriaxone had the lowest resistance rates at 0%.
CONCLUSION
Our findings indicate a high level of antibiotic resistance among the studied antibiotics. This high level of antibiotic resistance raises concerns and underscores the necessity for monitoring the use of antibiotics. Moreover, resistance to these antibiotics was more prevalent in samples isolated from animals compared to other sources. This highlights the importance of animal screening to detect the presence of drug-resistant isolates, with the ultimate goal of reducing antibiotic resistance and preventing the transmission of resistant strains to humans.
PubMed: 38860007
DOI: 10.3389/fvets.2024.1388790 -
The Brazilian Journal of Infectious... 2019Papiliotrema laurentii is one of several non-neoformans cryptococci that have rarely been associated with human infection, since it was previously considered saprophyte...
BACKGROUND
Papiliotrema laurentii is one of several non-neoformans cryptococci that have rarely been associated with human infection, since it was previously considered saprophyte and thought to be non-pathogenic to humans. Nevertheless, increasing number of reports of human infection have emerged in recent years, mostly in oncologic patients.
AIM
To report a case of a female patient with pyloric obstructive cancer with a catheter-related Papiliotrema laurentii blood stream infection and systematically review the available evidence on P. laurentii infection in humans.
METHODS
Retrieval of studies was based on Medical Subject Headings and Health Sciences Descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), BIREME (Biblioteca Regional de Medicina), LILACS (Latin American and Caribbean Health Sciences Literature), Cochrane Library for Systematic Reviews and Opengray.eu. There was no language or date of publication restrictions. The reference lists of the studies retrieved were searched manually.
RESULTS
The search strategy retrieved 1703 references. In the final analysis, 31 references were included, with the description of 35 cases. Every patient but one had a previous co-morbidity - 48.4 % of patients had a neoplasm. Amphotericin B was the most used treatment and only a single case of resistance to it was reported. Most patients were cured of the infection.
CONCLUSION
P. laurentii infection in humans is usually associated to neoplasia and multiple co-morbidities, and amphotericin B seems to be a reliable agent for treatment.
Topics: Aged; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Biopsy; Catheter-Related Infections; Cryptococcus; Female; Fluconazole; Humans; Piperacillin, Tazobactam Drug Combination; Stomach Neoplasms; Tomography, X-Ray Computed; Vancomycin
PubMed: 31738886
DOI: 10.1016/j.bjid.2019.10.005