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Antimicrobial Resistance and Infection... Sep 2020Clostridioides (Clostridium) difficile is an important pathogen of healthcare- associated diarrhea, however, an increase in the occurrence of C. difficile infection... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Clostridioides (Clostridium) difficile is an important pathogen of healthcare- associated diarrhea, however, an increase in the occurrence of C. difficile infection (CDI) outside hospital settings has been reported. The accumulation of antimicrobial resistance in C. difficile can increase the risk of CDI development and/or its spread. The limited number of antimicrobials for the treatment of CDI is matter of some concern.
OBJECTIVES
In order to summarize the data on antimicrobial resistance to C. difficile derived from humans, a systematic review and meta-analysis were performed.
METHODS
We searched five bibliographic databases: (MEDLINE [PubMed], Scopus, Embase, Cochrane Library and Web of Science) for studies that focused on antimicrobial susceptibility testing in C. difficile and were published between 1992 and 2019. The weighted pooled resistance (WPR) for each antimicrobial agent was calculated using a random- effects model.
RESULTS
A total of 111 studies were included. The WPR for metronidazole and vancomycin was 1.0% (95% CI 0-3%) and 1% (95% CI 0-2%) for the breakpoint > 2 mg/L and 0% (95% CI 0%) for breakpoint ≥32 μg/ml. Rifampin and tigecycline had a WPRs of 37.0% (95% CI 18-58%) and 1% (95% CI 0-3%), respectively. The WPRs for the other antimicrobials were as follows: ciprofloxacin 95% (95% CI 85-100%), moxifloxacin 32% (95% CI 25-40%), clindamycin 59% (95% CI 53-65%), amoxicillin/clavulanate 0% (0-0%), piperacillin/tazobactam 0% (0-0%) and ceftriaxone 47% (95% CI 29-65%). Tetracycline had a WPR 20% (95% CI 14-27%) and meropenem showed 0% (95% CI 0-1%); resistance to fidaxomicin was reported in one isolate (0.08%).
CONCLUSION
Resistance to metronidazole, vancomycin, fidaxomicin, meropenem and piperacillin/tazobactam is reported rarely. From the alternative CDI drug treatments, tigecycline had a lower resistance rate than rifampin. The high-risk antimicrobials for CDI development showed a high level of resistance, the highest was seen in the second generation of fluoroquinolones and clindamycin; amoxicillin/clavulanate showed almost no resistance. Tetracycline resistance was present in one fifth of human clinical C. difficile isolates.
Topics: Anti-Bacterial Agents; Clindamycin; Clostridioides difficile; Clostridium Infections; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Microbial Sensitivity Tests
PubMed: 32977835
DOI: 10.1186/s13756-020-00815-5 -
Journal of Global Antimicrobial... Mar 2021This study aimed to compare the efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for treating... (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for multiple drug-resistant and extensively drug-resistant Acinetobacter baumannii infections: A systematic review and network meta-analysis.
OBJECTIVES
This study aimed to compare the efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for treating multidrug-resistant or extensively drug-resistant Acinetobacter baumannii (MDR-AB or XDR-AB) infections.
METHODS
We systematically searched PubMed, Embase, Cochrane, and Web of Science (through March 30, 2020) for studies that examined high-dose sulbactam or colistin with additional antibacterial agents as therapy for patients with infections with MDR-AB and XDR-AB. Through a network meta-analysis (NMA), using both direct and indirect evidence, we determined risk ratios and 95% confidence intervals. Primary outcomes included clinical improvement, clinical cure, microbiological eradication, and mortality from any cause. Secondary outcomes included nephrotoxicity.
RESULTS
The NMA included 18 studies and 1835 patients. We found that high-dose sulbactam (≥6 g per day), combined with another single antibacterial agent (levofloxacin or tigecycline), which were the highest ranking in clinical improvement and clinical cure. Still colistin-based combination in drug-resistant Acinetobacter baumannii therapy occupied the main position (the number of studies and patients) in most studies. Colistin combined with additional antibacterial agents was associated with a higher risk of nephrotoxicity.
CONCLUSIONS
Therapeutic regimens including high-dose sulbactam in combination with additional antibacterial agents (including colistin) might be one of the promising options for the treatment of MDR-AB or XDR-AB infections and high-quality study will be needed to confirm clinical efficacy.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Network Meta-Analysis; Pharmaceutical Preparations; Sulbactam
PubMed: 32889142
DOI: 10.1016/j.jgar.2020.08.021 -
Clinical Microbiology and Infection :... Apr 2023The aim of the guidelines is to provide recommendations on perioperative antibiotic prophylaxis (PAP) in adult inpatients who are carriers of multidrug-resistant...
SCOPE
The aim of the guidelines is to provide recommendations on perioperative antibiotic prophylaxis (PAP) in adult inpatients who are carriers of multidrug-resistant Gram-negative bacteria (MDR-GNB) before surgery.
METHODS
These evidence-based guidelines were developed after a systematic review of published studies on PAP targeting the following MDR-GNB: extended-spectrum cephalosporin-resistant Enterobacterales, carbapenem-resistant Enterobacterales (CRE), aminoglycoside-resistant Enterobacterales, fluoroquinolone-resistant Enterobacterales, cotrimoxazole-resistant Stenotrophomonas maltophilia, carbapenem-resistant Acinetobacter baumannii (CRAB), extremely drug-resistant Pseudomonas aeruginosa, colistin-resistant Gram-negative bacteria, and pan-drug-resistant Gram-negative bacteria. The critical outcomes were the occurrence of surgical site infections (SSIs) caused by any bacteria and/or by the colonizing MDR-GNB, and SSI-attributable mortality. Important outcomes included the occurrence of any type of postsurgical infectious complication, all-cause mortality, and adverse events of PAP, including development of resistance to targeted (culture-based) PAP after surgery and incidence of Clostridioides difficile infections. The last search of all databases was performed until April 30, 2022. The level of evidence and strength of each recommendation were defined according to the Grading of Recommendations Assessment, Development and Evaluation approach. Consensus of a multidisciplinary expert panel was reached for the final list of recommendations. Antimicrobial stewardship considerations were included in the recommendation development.
RECOMMENDATIONS
The guideline panel reviewed the evidence, per bacteria, of the risk of SSIs in patients colonized with MDR-GNB before surgery and critically appraised the existing studies. Significant knowledge gaps were identified, and most questions were addressed by observational studies. Moderate to high risk of bias was identified in the retrieved studies, and the majority of the recommendations were supported by low level of evidence. The panel conditionally recommends rectal screening and targeted PAP for fluoroquinolone-resistant Enterobacterales before transrectal ultrasound-guided prostate biopsy and for extended-spectrum cephalosporin-resistant Enterobacterales in patients undergoing colorectal surgery and solid organ transplantation. Screening for CRE and CRAB is suggested before transplant surgery after assessment of the local epidemiology. Careful consideration of the laboratory workload and involvement of antimicrobial stewardship teams before implementing the screening procedures or performing changes in PAP are warranted. High-quality prospective studies to assess the impact of PAP among CRE and CRAB carriers performing high-risk surgeries are advocated. Future well-designed clinical trials should assess the effectiveness of targeted PAP, including the monitoring of MDR-GNB colonization through postoperative cultures using European Committee on Antimicrobial Susceptibility Testing clinical breakpoints.
Topics: Male; Adult; Humans; Gram-Negative Bacterial Infections; Antibiotic Prophylaxis; Prospective Studies; Gram-Negative Bacteria; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Carbapenems; Cephalosporins; Monobactams; Fluoroquinolones
PubMed: 36566836
DOI: 10.1016/j.cmi.2022.12.012 -
International Journal of Molecular... Oct 2022Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy,... (Meta-Analysis)
Meta-Analysis Review
Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy, resistance to these drugs occurs mainly due to mutations in the target genes (Folp1, RpoB and GyrA). It is important to monitor antimicrobial resistance in patients with leprosy. Therefore, we performed a meta-analysis of drug resistance in Mycobacterium leprae and the mutational profile of the target genes. In this paper, we limited the study period to May 2022 and searched PubMed, Web of Science (WOS), Scopus, and Embase databases for identified studies. Two independent reviewers extracted the study data. Mutation and drug-resistance rates were estimated in Stata 16.0. The results demonstrated that the drug-resistance rate was 10.18% (95% CI: 7.85-12.51). Subgroup analysis showed the highest resistance rate was in the Western Pacific region (17.05%, 95% CI:1.80 to 13.78), and it was higher after 2009 than before [(11.39%, 7.46-15.33) vs. 6.59% (3.66-9.53)]. We can conclude that the rate among new cases (7.25%, 95% CI: 4.65-9.84) was lower than the relapsed (14.26%, 95 CI%: 9.82-18.71). Mutation rates of Folp1, RpoB and GyrA were 4.40% (95% CI: 3.02-5.77), 3.66% (95% CI: 2.41-4.90) and 1.28% (95% CI: 0.87-1.71) respectively, while the rate for polygenes mutation was 1.73% (0.83-2.63). For further analysis, we used 368 drug-resistant strains as research subjects and found that codons (Ser, Pro, Ala) on RpoB, Folp1 and GyrA are the most common mutation sites in the determining region (DRDR). In addition, the most common substitution patterns of Folp1, RpoB, and GyrA are Pro→Leu, Ser→Leu, and Ala→Val. This study found that a higher proportion of patients has developed resistance to these drugs, and the rate has increased since 2009, which continue to pose a challenge to clinicians. In addition, the amino acid alterations in the sequence of the DRDR regions and the substitution patterns mentioned in the study also provide new ideas for clinical treatment options.
Topics: Humans; Rifampin; Dapsone; Leprostatic Agents; Ofloxacin; Drug Resistance, Bacterial; Mycobacterium leprae; Leprosy; Mutation; Amino Acids; Microbial Sensitivity Tests
PubMed: 36293307
DOI: 10.3390/ijms232012443 -
Emerging Microbes & Infections Dec 2022Antimicrobial resistance (AMR) and hospital-acquired infections (HAIs) are global health challenges. The burden of antibiotic resistance in HAIs is still unclear in low-... (Meta-Analysis)
Meta-Analysis
Antimicrobial resistance (AMR) and hospital-acquired infections (HAIs) are global health challenges. The burden of antibiotic resistance in HAIs is still unclear in low- and lower-middle-income countries (L-LMICs). This study summarizes recent data on antibiotic resistance in priority HAIs (ESKAPE-E) in L-LMICs and compares them with data from high-income countries (HICs). EMBASE, Web of Science, and Global Index Medicus were searched for studies on AMR patterns in HAIs published from 01/2010 to 10/2020. Random-effects meta-analyses were performed to obtain pooled estimates. In total, 163 eligible studies were included in the review and meta-analysis. The pooled methicillin resistance proportion in was 48.4% (95% confidence interval [95%CI] 41·7-55·2, n = 80). Pooled carbapenem resistance proportions were high in Gram-negative pathogens: : 16·6% (95%CI 10·7-23·4, n = 60); : 34·9% (95%CI 24·6-45·9, n = 50); : 37.1% (95%CI 24·6-45·9, n = 56); spp.: 51·2% (95%CI 27·5-74·7, n = 7); and 72·4% (95%CI 62·1-81·7%, n = 36). A higher resistance proportions were observed for third-generation cephalosporins: : 78·7% (95%CI 71·5-85·2, n = 46); 78·5% (95%CI 72·1-84·2%, n = 58); and spp.: 83·5% (95%CI 71·9-92·8, n = 8). We observed a high between-study heterogeneity (I > 80%), which could not be explained by our set of moderators. Pooled resistance proportions for Gram-negative pathogens were higher in L-LMICs than regional and national estimates from HICs. Patients in resource-constrained regions are particularly affected by AMR. To combat the high resistance to critical antibiotics in L-LMICs, and bridge disparities in health, it is crucial to strengthen local surveillance and the health systems in general.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Developing Countries; Drug Resistance, Bacterial; Hospitals; Humans; Klebsiella pneumoniae
PubMed: 35034585
DOI: 10.1080/22221751.2022.2030196 -
Antimicrobial Resistance and Infection... Mar 2022Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients hospitalized with COVID-19 which potentially acts as a catalyst for the development of antimicrobial resistance (AMR).
OBJECTIVES
We conducted a systematic review and meta-analysis during the first 18 months of the pandemic to quantify the prevalence and types of resistant co-infecting organisms in patients with COVID-19 and explore differences across hospital and geographic settings.
METHODS
We searched MEDLINE, Embase, Web of Science (BioSIS), and Scopus from November 1, 2019 to May 28, 2021 to identify relevant articles pertaining to resistant co-infections in patients with laboratory confirmed SARS-CoV-2. Patient- and study-level analyses were conducted. We calculated pooled prevalence estimates of co-infection with resistant bacterial or fungal organisms using random effects models. Stratified meta-analysis by hospital and geographic setting was also performed to elucidate any differences.
RESULTS
Of 1331 articles identified, 38 met inclusion criteria. A total of 1959 unique isolates were identified with 29% (569) resistant organisms identified. Co-infection with resistant bacterial or fungal organisms ranged from 0.2 to 100% among included studies. Pooled prevalence of co-infection with resistant bacterial and fungal organisms was 24% (95% CI 8-40%; n = 25 studies: I = 99%) and 0.3% (95% CI 0.1-0.6%; n = 8 studies: I = 78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and multi-drug resistant Candida auris were most commonly reported. Stratified analyses found higher proportions of AMR outside of Europe and in ICU settings, though these results were not statistically significant. Patient-level analysis demonstrated > 50% (n = 58) mortality, whereby all but 6 patients were infected with a resistant organism.
CONCLUSIONS
During the first 18 months of the pandemic, AMR prevalence was high in COVID-19 patients and varied by hospital and geography although there was substantial heterogeneity. Given the variation in patient populations within these studies, clinical settings, practice patterns, and definitions of AMR, further research is warranted to quantify AMR in COVID-19 patients to improve surveillance programs, infection prevention and control practices and antimicrobial stewardship programs globally.
Topics: Anti-Bacterial Agents; Antifungal Agents; Bacteria; Bacterial Infections; COVID-19; Drug Resistance, Bacterial; Drug Resistance, Fungal; Fungi; Humans; Mycoses; SARS-CoV-2
PubMed: 35255988
DOI: 10.1186/s13756-022-01085-z -
PloS One 2020Currently, various tools exist to evaluate knowledge and awareness of antibiotic use and antimicrobial resistance (AMR) and are applied by various organizations....
BACKGROUND
Currently, various tools exist to evaluate knowledge and awareness of antibiotic use and antimicrobial resistance (AMR) and are applied by various organizations. Previous systematic reviews have focused mainly on study findings such as levels of knowledge and AMR awareness. However, the survey procedures and data instruments used ought to be scrutinized as well, since they are important contributors to credible results. This review aims to assess the study methods and procedures of existing population-based surveys and explore key components which determine the general population's levels of knowledge and awareness of antibiotic use and AMR.
METHODS
We searched existing literature for population -based surveys which sought knowledge and awareness of antibiotic use or AMR in the general population. Databases searched included Ovid, MEDLINE and EMBASE, PsycINFO and Scopus, domestic journals and gray literature sources. Population-based cross-sectional studies published in English or Thai from January 2000 to December 2018 were included in the review. Quality assessment was conducted using the 'Appraisal Tool for Cross-Sectional Studies' (AXIS).
RESULTS
All 22 studies included in the analysis had clear objectives focusing on assessing people's levels of knowledge, awareness, attitudes and behavior relating to antibiotic use and awareness of AMR. These studies had employed appropriate methodologies for population-based cross-sectional surveys relative to research questions. More than half of studies (14 out of 22) had scientifically soundly designed methodologies which captured the representativeness of the population; whereas the remaining studies had unclear sample size estimations, inappropriate sample frames and selection biases. Half of the studies had tested the validity and reliability of the questionnaire. The common questions used by these surveys were categorized into four themes: behavior related to antibiotic use, knowledge and awareness of antibiotic use, knowledge and awareness of AMR and others such as receiving information about antibiotic use and AMR or cross-cutting issues like self-medication.
CONCLUSION
This review identified four key features of good practices in antibiotic use and awareness surveys: a) clear survey objective; b) scientifically sound sampling techniques ensuring representativeness; c) strategies for recruitment of samples and survey administration methods; and d) credible measurement to prevent non-sampling biases. During questionnaire design, the health systems context in terms of access to health services and antibiotics should be taken into account. In conclusion, to maximize the use of surveys, the application of findings in surveys and associated factors related to antibiotic use and AMR should primarily generate public health interventions and target specific groups to make progress in solving AMR problems.
Topics: Anti-Bacterial Agents; Awareness; Bacterial Infections; Databases, Factual; Drug Resistance, Bacterial; Drug Resistance, Microbial; Health Knowledge, Attitudes, Practice; Humans; Surveys and Questionnaires; Thailand
PubMed: 31945117
DOI: 10.1371/journal.pone.0227973 -
Journal of Clinical Pharmacy and... Jun 2021Meropenem, a carbapenem antibiotic, is widely prescribed for the treatment of life-threatening infections. The main parameter associated with its therapeutic success is...
WHAT IS KNOWN AND OBJECTIVE
Meropenem, a carbapenem antibiotic, is widely prescribed for the treatment of life-threatening infections. The main parameter associated with its therapeutic success is the percentage of time that the levels remain above the minimum inhibitory concentration. Inadequate levels of meropenem can lead to therapeutic failure and increase the possibility of microbial resistance. The employment of strategies involving dose regimens and drug pharmacodynamics has become increasingly important to optimize therapies. In the present study, we conducted a review with the purpose of assembling information about the clinical use of meropenem and therapeutic drug monitoring.
METHODS
A literature review emphasizing the application of therapeutic drug monitoring (TDM) of meropenem in clinical practice has been done. To identify articles related to the topic, we performed a standardized search from January 21, 2020 to December 21, 2020, using specific descriptors in PubMed, Lilacs and Embase.
RESULTS AND DISCUSSION
In total, 35 studies were included in the review. The daily dose of meropenem commonly ranged from 3 to 6 g/day. Critically ill patients and those with impaired renal function appear to be the most suitable patients for the application of meropenem TDM, in order to guide therapy. We observed that most of the studies recommend TDM and that, in nine locations, the TDM of meropenem and of other beta-lactams is a routine practice. TDM data can help to maximize the clinical outcomes of the treatment with meropenem. It can also improve the patient care by providing suitable levels of meropenem, guiding the most appropriate dose regimens, which is the main parameter associated with therapeutic success.
WHAT IS NEW AND CONCLUSION
The findings from this review suggest that the therapeutic monitoring of meropenem can be beneficial, since it adjusts the treatment and aids clinical outcomes. It does so by indicating the appropriate dosage and preventing failure, toxicity and possible antimicrobial resistance. The multidisciplinary effort, basic knowledge and communication among the medical team are also essential.
Topics: Anti-Bacterial Agents; Critical Illness; Drug Monitoring; Drug Resistance, Microbial; Humans; Meropenem; Microbial Sensitivity Tests; Severity of Illness Index
PubMed: 33533509
DOI: 10.1111/jcpt.13369 -
JAMA Nov 2022The effectiveness of selective decontamination of the digestive tract (SDD) in critically ill adults receiving mechanical ventilation is uncertain. (Meta-Analysis)
Meta-Analysis
Association Between Selective Decontamination of the Digestive Tract and In-Hospital Mortality in Intensive Care Unit Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis.
IMPORTANCE
The effectiveness of selective decontamination of the digestive tract (SDD) in critically ill adults receiving mechanical ventilation is uncertain.
OBJECTIVE
To determine whether SDD is associated with reduced risk of death in adults receiving mechanical ventilation in intensive care units (ICUs) compared with standard care.
DATA SOURCES
The primary search was conducted using MEDLINE, EMBASE, and CENTRAL databases until September 2022.
STUDY SELECTION
Randomized clinical trials including adults receiving mechanical ventilation in the ICU comparing SDD vs standard care or placebo.
DATA EXTRACTION AND SYNTHESIS
Data extraction and risk of bias assessments were performed in duplicate. The primary analysis was conducted using a bayesian framework.
MAIN OUTCOMES AND MEASURES
The primary outcome was hospital mortality. Subgroups included SDD with an intravenous agent compared with SDD without an intravenous agent. There were 8 secondary outcomes including the incidence of ventilator-associated pneumonia, ICU-acquired bacteremia, and the incidence of positive cultures of antimicrobial-resistant organisms.
RESULTS
There were 32 randomized clinical trials including 24 389 participants in the analysis. The median age of participants in the included studies was 54 years (IQR, 44-60), and the median proportion of female trial participants was 33% (IQR, 25%-38%). Data from 30 trials including 24 034 participants contributed to the primary outcome. The pooled estimated risk ratio (RR) for mortality for SDD compared with standard care was 0.91 (95% credible interval [CrI], 0.82-0.99; I2 = 33.9%; moderate certainty) with a 99.3% posterior probability that SDD reduced hospital mortality. The beneficial association of SDD was evident in trials with an intravenous agent (RR, 0.84 [95% CrI, 0.74-0.94]), but not in trials without an intravenous agent (RR, 1.01 [95% CrI, 0.91-1.11]) (P value for the interaction between subgroups = .02). SDD was associated with reduced risk of ventilator-associated pneumonia (RR, 0.44 [95% CrI, 0.36-0.54]) and ICU-acquired bacteremia (RR, 0.68 [95% CrI, 0.57-0.81]). Available data regarding the incidence of positive cultures of antimicrobial-resistant organisms were not amenable to pooling and were of very low certainty.
CONCLUSIONS AND RELEVANCE
Among adults in the ICU treated with mechanical ventilation, the use of SDD compared with standard care or placebo was associated with lower hospital mortality. Evidence regarding the effect of SDD on antimicrobial resistance was of very low certainty.
Topics: Humans; Anti-Infective Agents; Bacteremia; Bayes Theorem; Gastrointestinal Tract; Hospital Mortality; Intensive Care Units; Pneumonia, Ventilator-Associated; Respiration, Artificial; Critical Illness; Drug Resistance, Microbial; Infection Control
PubMed: 36286098
DOI: 10.1001/jama.2022.19709 -
International Journal of Antimicrobial... May 2021The superiority of combination therapy for carbapenem-resistant Gram-negative bacilli (CR-GNB) infections remains controversial. In vitro models may predict the efficacy... (Meta-Analysis)
Meta-Analysis
The superiority of combination therapy for carbapenem-resistant Gram-negative bacilli (CR-GNB) infections remains controversial. In vitro models may predict the efficacy of antibiotic regimens against CR-GNB. A systematic review and meta-analysis was performed including pharmacokinetic/pharmacodynamic (PK/PD) and time-kill (TK) studies examining the in vitro efficacy of antibiotic combinations against CR-GNB [PROSPERO registration no. CRD42019128104]. The primary outcome was in vitro synergy based on the effect size (ES): high, ES ≥ 0.75, moderate, 0.35 < ES < 0.75; low, ES ≤ 0.35; and absent, ES = 0). A network meta-analysis assessed the bactericidal effect and re-growth rate (secondary outcomes). An adapted version of the ToxRTool was used for risk-of-bias assessment. Over 180 combination regimens from 136 studies were included. The most frequently analysed classes were polymyxins and carbapenems. Limited data were available for ceftazidime/avibactam, ceftolozane/tazobactam and imipenem/relebactam. High or moderate synergism was shown for polymyxin/rifampicin against Acinetobacter baumannii [ES = 0.91, 95% confidence interval (CI) 0.44-1.00], polymyxin/fosfomycin against Klebsiella pneumoniae (ES = 1.00, 95% CI 0.66-1.00) and imipenem/amikacin against Pseudomonas aeruginosa (ES = 1.00, 95% CI 0.21-1.00). Compared with monotherapy, increased bactericidal activity and lower re-growth rates were reported for colistin/fosfomycin and polymyxin/rifampicin in K. pneumoniae and for imipenem/amikacin or imipenem/tobramycin against P. aeruginosa. High quality was documented for 65% and 53% of PK/PD and TK studies, respectively. Well-designed in vitro studies should be encouraged to guide the selection of combination therapies in clinical trials and to improve the armamentarium against carbapenem-resistant bacteria.
Topics: Amikacin; Anti-Bacterial Agents; Azabicyclo Compounds; Carbapenems; Ceftazidime; Cephalosporins; Colistin; Drug Combinations; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; In Vitro Techniques; Microbial Sensitivity Tests; Polymyxins; Rifampin; Tazobactam; Tobramycin
PubMed: 33857539
DOI: 10.1016/j.ijantimicag.2021.106344