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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 -
The Journal of Hospital Infection May 2024Bacteria commonly adhere to surfaces and produce polymeric material to encase the attached cells to form communities called biofilms. Within these biofilms, bacteria can... (Review)
Review
Bacteria commonly adhere to surfaces and produce polymeric material to encase the attached cells to form communities called biofilms. Within these biofilms, bacteria can appear to be many times more resistant to antibiotics or disinfectants. This systematic review explores the prevalence and microbial profile associated with biofilm production of bacteria isolated from endotracheal tubes and its associations with antimicrobial resistance. A comprehensive search was performed on databases PubMed, Embase, and Google Scholar for relevant articles published between 1 January 2000 and 31 December 2022. The relevant articles were exported to Mendeley Desktop 1.19.8 and screened by title and abstract, followed by full text screening based on the eligibility criteria of the study. Quality assessment of the studies was performed using the Newcastle-Ottawa Scale (NOS) customized for cross-sectional studies. Furthermore, the prevalence of antimicrobial resistance in biofilm-producers isolated from endotracheal tube specimens was investigated. Twenty studies encompassing 981 endotracheal tubes met the eligibility criteria. Pseudomonas spp. and Acinetobacter spp. were predominant isolates among the biofilm producers. These biofilms provided strong resistance against commonly used antibiotics. The highest resistance rate observed in Pseudomonas spp. was against fluoroquinolones whereas the least resistance was seen against piperacillin-tazobactam. A similar trend of susceptibility was observed in Acinetobacter spp. with a very high resistance rate against fluoroquinolones, third-generation cephalosporins and carbapenems. In conclusion, endotracheal tubes were associated with colonization by biofilm forming bacteria with varying levels of antimicrobial resistance. Biofilms may promote the occurrence of recalcitrant infections in endotracheal tubes which need to be managed with appropriate protocols and antimicrobial stewardship. Research focus should shift towards meticulous exploration of biofilm-associated infections to improve detection and management.
Topics: Biofilms; Humans; Intubation, Intratracheal; Drug Resistance, Bacterial; Anti-Bacterial Agents; Bacteria
PubMed: 38522561
DOI: 10.1016/j.jhin.2024.03.004 -
Journal of Critical Care Aug 2019To summarize selected original critical care pharmacotherapy research published in 2018.
PURPOSE
To summarize selected original critical care pharmacotherapy research published in 2018.
MATERIALS AND METHODS
The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 32 journals monthly for impactful articles and reviewed 100 articles during 2018. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria were applied to all relevant articles included in the monthly CCPLU. Articles with a 1A grade, including one clinical practice guideline, two meta-analyses, and ten original research trials, were selected for review.
RESULTS
Clinical practice guidelines for the management of pain, agitation, delirium, immobility, and sleep disruption were summarized. Meta-analyses on the role of corticosteroids in sepsis and early enteral nutrition were reviewed. Included original research trials evaluated corticosteroids in sepsis, enteral and parenteral nutrition in patients with shock, tenecteplase in acute ischemic stroke, antipsychotics for the treatment of intensive care unit delirium, vasopressors in cardiogenic shock, balanced crystalloids and saline for fluid administration, and meropenem and piperacillin-tazobactam for treatment of resistant Gram-negative organisms.
CONCLUSION
This clinical review and expert commentary of impactful critical care pharmacotherapy publications in 2018 provides perspectives and insights for the critical care practitioner.
Topics: Brain Ischemia; Critical Care; Delirium; Drug Therapy; Enteral Nutrition; Fluid Therapy; Humans; Intensive Care Units; Meta-Analysis as Topic; Pain; Periodicals as Topic; Practice Guidelines as Topic; Sepsis; Stroke
PubMed: 31100708
DOI: 10.1016/j.jcrc.2019.04.029 -
European Journal of Hospital Pharmacy :... Nov 2022In order to use aseptically prepared elastomeric infusers, outpatient parenteral antimicrobial therapy (OPAT) services require extended stability data for antimicrobial...
Systematic review of the stability of antimicrobial agents in elastomeric devices for outpatient parenteral antimicrobial therapy services based on NHS Yellow Cover Document standards.
BACKGROUND
In order to use aseptically prepared elastomeric infusers, outpatient parenteral antimicrobial therapy (OPAT) services require extended stability data for antimicrobial agents to assign a product shelf-life. In the UK, the relevant standards for stability testing and shelf-life assignment are published in 'A Standard Protocol for Deriving and Assessment of Stability-Part 1 (Aseptic Preparations-Small Molecules), commonly called the Yellow Covered Document (YCD). A previous systematic review published in 2017 failed to identify data on the stability of antimicrobials in elastomeric devices for OPAT services that met YCD requirements in force at the time. The aim of this review was to update that search, following a subsequent change to YCD requirements in 2017 and 2019 and expand that dataset to identify progress made in providing assurance about the stability of antimicrobial agents for OPAT services.
METHODS
Searches were undertaken for papers relating to extended stability of antimicrobials. Citations were included when antimicrobial shelf-life was assessed using a stability-indicating method and considered a period of storage, either refrigerated or at room temperature, followed by in-use testing at a temperature at or above 32°C.
RESULTS
Of 267 initial citations, six met the inclusion criteria and underwent full text review for data extraction. Included antimicrobials were cefazolin, ceftazidime, piperacillin/tazobactam, flucloxacillin and ceftolozane/tazobactam. Of these, only flucloxacillin and piperacillin demonstrated YCD compliant stability over the 24-hour infusion period while cefazolin, ceftazidime and ceftolozane/tazobactam could be infused over 12-hour period.
CONCLUSIONS
Contrary to the position found in 2017 review, high-quality data are now available to support the use of a number of antimicrobial agents in extended infusion in elastomeric devices for OPAT services. There is a need to expand the dataset, as well as developing international consensus on the ideal parameters for stability assessment of such infusions in elastomeric devices.
Topics: Humans; Anti-Bacterial Agents; Anti-Infective Agents; Cefazolin; Ceftazidime; Floxacillin; Outpatients; Piperacillin; State Medicine; Tazobactam
PubMed: 33990388
DOI: 10.1136/ejhpharm-2021-002729 -
Langenbeck's Archives of Surgery Nov 2022Septic complications after pancreatic surgery are common. However, it remains unclear if and how a shift of the microbiological spectrum affects morbidity. The aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Septic complications after pancreatic surgery are common. However, it remains unclear if and how a shift of the microbiological spectrum affects morbidity. The aim of the present study was to assess the microbiological spectrum and antibiotic resistance patterns and their impact on outcome.
METHODS
We conducted a retrospective study including patients undergoing pancreatic surgery at our center between 2005 and 2018. A systematic literature review and descriptive meta-analysis of the published and original data was performed according to the PRISMA guidelines.
RESULTS
A total of 318 patients were included in the analysis. Patients with biliary drainage had a significantly higher incidence of bacterobilia (93% vs. 25%) and received preoperative antibiotics (46% vs. 12%). The analyzed bile cultures showed no resistance to piperacillin/tazobactam, fluoroquinolones, or carbapenems. Resistance to cefuroxime was seen in 58% of the samples of patients without biliary drainage (NBD) and 93% of the samples of those with drainage (BD). In general, there was no significant difference in overall postoperative morbidity. However, superficial surgical site infections (SSIs) were significantly more common in the BD group. We included a total of six studies and our own data (1627 patients) in the descriptive meta-analysis. The percentage of positive bile cultures ranged from 53 to 81%. In patients with BD, the most frequent microorganisms were Enterococcus spp. (58%), Klebsiella spp. (29%), and E. coli (27%). Almost all studies demonstrated resistance to first- and second-generation cephalosporins and to third- and fourth-generation cephalosporins for patients with BD.
CONCLUSION
A change in perioperative antibiotic strategy according to local resistance patterns, especially after BD, might be useful for patients undergoing pancreatic surgery. Appropriate perioperative antibiotic coverage may help to prevent abdominal infectious complications and especially superficial SSIs.
Topics: Humans; Bile; Retrospective Studies; Escherichia coli; Preoperative Care; Pancreaticoduodenectomy; Anti-Bacterial Agents; Drug Resistance, Microbial; Cephalosporins; Surgical Wound Infection
PubMed: 35654872
DOI: 10.1007/s00423-022-02559-9 -
Infection & Chemotherapy Mar 2022The use of antibiotics in diabetic foot ulcer infections (DFUI) is essential in reducing morbidity. Optimal administration of antibiotics can improve clinical outcomes...
BACKGROUND
The use of antibiotics in diabetic foot ulcer infections (DFUI) is essential in reducing morbidity. Optimal administration of antibiotics can improve clinical outcomes and reduce the risk of antibiotic resistance. This study aims to review the efficacy, in terms of clinical cure, of various regimens and the duration of antibiotic administration in DFUI patients, based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The efficacy based on microbiological response is also reviewed as the secondary outcome.
MATERIALS AND METHODS
We used three databases, namely PubMed, Scopus, and ScienceDirect, to search for randomized controlled trials (RCTs) in patients with DFUI who required antibiotics.
RESULTS
A total of 16 studies were included in the systematic review. The study locations and bacterial patterns varied, with the most common pathogen being . Most studies did not demonstrate a significant difference in clinical cure and pathogen eradication, either in the comparison between systemic and topical antibiotics or in the duration of administration. Some studies had similar characteristics and were analyzed to conclude. These studies showed that ertapenem had comparable efficacy to piperacillin/tazobactam. Similar results were also conducted from studies of piperacillin-tazobactam+amoxicillin-clavulanic acid moxifloxacin.
CONCLUSION
Most studies have heterogeneous characteristics, possibly due to differences in research location. Therefore, there is no strong evidence to recommend a specific antibiotic with the highest efficacy. However, since all included studies are RCTs, this review provides a good summary in considering antibiotic choices when treating DFUI patients.
PubMed: 35384424
DOI: 10.3947/ic.2021.0144 -
Revista Do Instituto de Medicina... 2021The aim of this systematic review was to determine the causal role of Erysipelatoclostridium ramosum in specific invasive infections in humans, and to assess the...
The aim of this systematic review was to determine the causal role of Erysipelatoclostridium ramosum in specific invasive infections in humans, and to assess the clinical outcome of antibiotic therapy used to treat them. Several electronic databases were systematically searched for clinical trials, observational studies or individual cases on patients of any age and gender with a systemic inflammatory response syndrome (SIRS) due to E. ramosum isolated from body fluids or tissues in which it is not normally present. Only reports identifying E. ramosum as the only microorganism isolated from a patient with SIRS were included. This systematic review included 15 studies reporting 19 individual cases in which E. ramosum caused invasive infections in various tissues, mainly in immunocompromised patients. E. ramosum was most often isolated by blood cultures and identified by specific biochemical tests. Severe infections caused by E. ramosum were in most cases effectively treated with antibiotics, except in two patients, one of whom died. More than one isolate of E. ramosum exhibited 100% susceptibility to metronidazole, amoxicillin/clavulanate and piperacillin/tazobactam. On the other hand, individual resistance of this bacterium to penicillin, ciprofloxacin, clindamycin, imipenem and ertapenem was reported. This systematic review confirmed the clinical relevance of E. ramosum as a cause of a number of severe infections mainly in immunocompromised inpatients. Metronidazole and meropenem appear to be the antibiotics of choice that should be used in combination or as monotherapy to treat E. ramosum infections, depending on the type and severity of the infection.
Topics: Anti-Bacterial Agents; Firmicutes; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests
PubMed: 33852713
DOI: 10.1590/S1678-9946202163030 -
Journal of Global Antimicrobial... Sep 2019This meta-analysis aimed to evaluate the current prevalence and trends over the past 10 years of Pseudomonas aeruginosa (P. aeruginosa) antimicrobial resistance. Two... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This meta-analysis aimed to evaluate the current prevalence and trends over the past 10 years of Pseudomonas aeruginosa (P. aeruginosa) antimicrobial resistance. Two researches independently searched two national (ULAKBİM, Türk Medline) and two international databases (PubMed, Web of Science) to identify studies on P. aeruginosa resistance to antimicrobials from 2007 to 2017.
METHODS
Homogeneity across studies was assessed using Cochrane guidelines, and total variability due to between-study variations was reflected in the I index. A random effects model was developed to estimate the antimicrobial resistance rates and their corresponding 95% CI. Pooled antibiotic resistance rates between 2007-2011 and 2012-2016 were compared to calculate the change in antibiotic resistance over time. Electronic searches with MeSH terms and text words identified 1017 papers. After applying exclusion and inclusion criteria, 45 articles were selected.
RESULTS
Pooled resistance prevalence of P. aeruginosa to piperacillin-tazobactam, ceftazidime, cefepime, meropenem, imipenem, ciprofloxacin, gentamicin, amikacin, tobramycin and colistin were 33.9%, 38.6%, 35.6%, 30.1%, 28.0%, 30.7%, 28.2%, 17.8%, 15.7% and 2.2%, respectively. The resistance rates of piperacillin, piperacillin-tazobactam, imipenem, meropenem, amikacin and colistin significantly increased in the second 5 years (P<0.05); however, gentamicin, tobramycin and ciprofloxacin resistance rates significantly decreased (P<0.05). Comparing the resistance rates between the isolates of intensive care unit (ICU) patients and non-ICU patients, meropenem and piperacillin-tazobactam resistance in ICU isolates were significantly higher than non-ICU (P<0.05).
CONCLUSIONS
These results suggest that antibiotic resistance is high in P. aeruginosa and the trends in antimicrobial resistance continue to increase, mainly in carbapenems and penicillins, in Turkey.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Microbial Sensitivity Tests; Prevalence; Pseudomonas Infections; Pseudomonas aeruginosa; Turkey
PubMed: 30753904
DOI: 10.1016/j.jgar.2019.01.032 -
International Journal of Antimicrobial... Dec 2019The increasing incidence of infections caused by extended-spectrum beta-lactamase (ESBL)/AmpC-producing bacteria leads to increasing use of carbapenems and risk of... (Meta-Analysis)
Meta-Analysis
Clinical cure rate and cost-effectiveness of carbapenem-sparing beta-lactams vs. meropenem for Gram-negative infections: A systematic review, meta-analysis, and cost-effectiveness analysis.
The increasing incidence of infections caused by extended-spectrum beta-lactamase (ESBL)/AmpC-producing bacteria leads to increasing use of carbapenems and risk of carbapenem resistance. Treatment success of carbapenem-sparing beta-lactams (CSBs) for ESBL infections is unclear. The aim of this study was to appraise the clinical cure rate and estimate the cost-effectiveness of meropenem vs. CSBs (piperacillin-tazobactam, temocillin, ceftazidime-avibactam, and ceftolozane-tazobactam) for urinary tract infections (UTIs) or intra-abdominal infections (IAIs) due to ESBL/AmpC-producing bacteria. A systematic literature search of the Cochrane library, EMBASE, PubMed, and Web of Science was conducted to identify studies assessing the clinical cure rate of the antibiotics. To assess the cost-effectiveness of CSBs vs. meropenem, a combined decision analytic and Markov model was probabilistically analysed over a 5-year period. The main outcome was presented as the incremental cost-effectiveness ratio and evaluated with a threshold of €20 000 per life year gained (LYG). From 656 identified articles, 17 and 14 studies were included in the qualitative synthesis and quantitative synthesis, respectively. A clinical cure of ceftazidime-avibactam and ceftolozane-tazobactam was comparable to meropenem in patients with complicated IAIs (cIAIs) due to ESBL (Risk ratio [RR]=1·04, 95% confidence interval [CI]=0·95-1·13). Both temocillin and ceftolozane-tazobactam were deemed cost-effective compared to meropenem with €157·58 and €13 398·34 per LYG, respectively, in patients with UTIs due to ESBL. However, only ceftazidime-avibactam (plus metronidazole) was cost-effective for the treatment of IAIs, with €16 916·77 per LYG. These results show that several CSBs can be considered as viable candidates for the treatment of UTIs and IAIs caused by ESBL.
Topics: Anti-Bacterial Agents; Cost-Benefit Analysis; Gram-Negative Bacterial Infections; Humans; Meropenem; beta-Lactams
PubMed: 31284041
DOI: 10.1016/j.ijantimicag.2019.07.003 -
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