-
Clinical Microbiology and Infection :... Mar 2021There is inconsistency between many guidelines in the recommended dose reduction of renally cleared antibiotics in patients with impaired renal function.
BACKGROUND
There is inconsistency between many guidelines in the recommended dose reduction of renally cleared antibiotics in patients with impaired renal function.
OBJECTIVES
This systematic review summarizes the available evidence on the adequacy of the recommended dose reduction in terms of achieving sufficient antibiotic drug exposure or pharmacokinetic/pharmacodynamic target attainment after treatment with these reduced doses.
DATA SOURCES
We systematically searched Ovid Medline and Embase from inception (respectively 1946 and 1947) through July 2019.
STUDY ELIGIBILITY CRITERIA
All studies reporting antibiotic drug exposure and/or pharmacokinetic/pharmacodynamic (PK/PD) target attainment after dose reduction of antibiotics in patients with impaired renal function.
PARTICIPANTS
Adult patients with or without infections.
INTERVENTIONS
Administration of reduced doses of antibiotics (orally, intravenously or intramuscularly).
METHODS
The reduced dose was considered adequate when the most relevant parameters of drug exposure or PK/PD target attainment in patients with impaired renal function were within a range of 80% to 125% of that patients with adequate renal function receiving a regular dose (reference) or when PK/PD target attainment was attained in at least 90% of the patients with impaired renal function, regardless of the lack of a reference group.
RESULTS
Twenty-seven of the 4202 identified studies were included. The quality of 15 of 27 studies was fair, and most studies were of β-lactams (12/27). Best evidence was available for meropenem: four studies were included, of which two studies were of good quality. Drug exposure for meropenem is 158% to 286% higher in patients with impaired renal function receiving reduced doses compared to patients with adequate renal function receiving regular doses. For all other antibiotics, a maximum of one good-quality study could be identified.
CONCLUSIONS
No good-quality evidence on the recommended dose reduction of renally cleared antibiotics in patients with impaired renal function is present, with the exception of meropenem.
Topics: Anti-Bacterial Agents; Drug Tapering; Humans; Renal Insufficiency
PubMed: 33290864
DOI: 10.1016/j.cmi.2020.11.032 -
BMC Infectious Diseases Nov 2020Helicobacter cinaedi is rarely identified as a cause of infected aneurysms; however, the number of reported cases has been increasing over several decades, especially in...
BACKGROUND
Helicobacter cinaedi is rarely identified as a cause of infected aneurysms; however, the number of reported cases has been increasing over several decades, especially in Japan. We report three cases of aortic aneurysm infected by H. cinaedi that were successfully treated using meropenem plus surgical stent graft replacement or intravascular stenting. Furthermore, we performed a systematic review of the literature regarding aortic aneurysm infected by H. cinaedi.
CASE PRESENTATION
We present three rare cases of infected aneurysm caused by H. cinaedi in adults. Blood and tissue cultures and 16S rRNA gene sequencing were used for diagnosis. Two patients underwent urgent surgical stent graft replacement, and the other patient underwent intravascular stenting. All three cases were treated successfully with intravenous meropenem for 4 to 6 weeks.
CONCLUSIONS
These cases suggest that although aneurysms infected by H. cinaedi are rare, clinicians should be aware of H. cinaedi as a potential causative pathogen, even in immunocompetent patients. Prolonged incubation periods for blood cultures are necessary for the accurate detection of H. cinaedi.
Topics: Adult; Aged; Aged, 80 and over; Aneurysm, Infected; Anti-Bacterial Agents; Aortic Aneurysm; Blood Culture; Female; Follow-Up Studies; Helicobacter; Helicobacter Infections; Humans; Immunocompromised Host; Japan; Male; Middle Aged; RNA, Ribosomal, 16S; Tomography, X-Ray Computed; Treatment Outcome; beta-Lactams
PubMed: 33203370
DOI: 10.1186/s12879-020-05582-7 -
Medicine Oct 2020Febrile neutropenia (FN) in cancer patients can be life threatening and require the timely antimicrobial agents treatment. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Febrile neutropenia (FN) in cancer patients can be life threatening and require the timely antimicrobial agents treatment.
METHODS
To compare the effectiveness and safety of carbapenems versus β-lactams for FN. PubMed, Medline (Ovid SP), Cochrane CENTRAL, and Embase were searched up to March 2019. FN in patients due to undergoing chemotherapy and treated with carbapenems and β-lactams were included. Odds ratio (OR) and 95% confidence interval (CI) were estimated.
RESULTS
Fifty randomized controlled trials (RCTs) studies involving 10,995 participants were included. Carbapenems were more likely to experience treatment success without modification (OR = 1.34, 95% CI = 1.24-1.46) compared with β-lactams. Meropenem (OR = 1.36, 95% CI = 1.18-1.56; OR = 1.24, 95% CI = 1.01-1.53), imipenem/cilastatin (OR = 1.40, 95% CI = 1.19-1.65; OR = 1.31, 95% CI = 1.04-1.67) showed higher effectiveness from that by β-lactams monotherapy or in combination with aminoglycoside, respectively. Carbapenems-aminoglycoside combination therapy does not provide an advantage over carbapenems alone. Meropenem showed similar risk of adverse events (AEs) versus β-lactams. Imipenem/cilastatin was related to higher risk of AEs compared with β-lactams. There was no significant difference between carbapenems and β-lactams monotherapy or in combination.
CONCLUSION
Meropenem and imipenem/cilastatin monotherapy appears to be available treatment for FN compared with β-lactams. Imipenem/cilastatin was related to higher risk of AEs. Balancing the evidence for drug efficacy and side effects, meropenem monotherapy appears to be available treatment for FN. Individual centers should select the best matching therapy regimens according to local epidemiology and susceptibility patterns.
Topics: Anti-Bacterial Agents; Carbapenems; Drug Therapy, Combination; Febrile Neutropenia; Humans; Randomized Controlled Trials as Topic; beta-Lactams
PubMed: 33120768
DOI: 10.1097/MD.0000000000022725 -
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 -
Advances in Clinical and Experimental... Aug 2020The antibiotic meropenem is commonly administered to patients with sepsis and septic shock. The aim of this study was to conduct a meta-analysis to evaluate the clinical... (Meta-Analysis)
Meta-Analysis
The antibiotic meropenem is commonly administered to patients with sepsis and septic shock. The aim of this study was to conduct a meta-analysis to evaluate the clinical efficacy and safety of continuous compared to intermittent meropenem infusion for the treatment of sepsis. Electronic databases such as PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI) were researched to collect clinical trials comparing continuous and intermittent infusion of meropenem in patients with sepsis. After data extraction and quality assessment of the included studies, Stata v. 12.0 software (Stata Corporation LLC, College Station, USA) was used for a meta-analysis of mortality, clinical cure, microbiological eradication, and safety. Seven studies with a total of 1,191 participants met the inclusion criteria and were included in the meta-analysis. The meta-analysis showed that continuous meropenem infusion was superior to intermittent infusion in terms of mortality (combined risk ratio (RR) = 0.66, 95% confidence interval (95% CI) = 0.46-0.98, p = 0.03), clinical cure rate (combined RR = 1.15, 95% CI = 1.02-1.30, p = 0.026) and microbiological eradication (combined RR = 1.20, 95% CI = 1.01-1.42, p = 0.04), although it may increase the incidence of some adverse events (AEs). Compared with intermittent dosing, administration of meropenem antibiotics through continuous infusion in patients with sepsis is associated with decreased hospital mortality, increased clinical cure rates and greater microbiological eradication. Further high-quality studies should be conducted to confirm our findings.
Topics: Anti-Bacterial Agents; China; Humans; Infusions, Intravenous; Meropenem; Sepsis
PubMed: 32783408
DOI: 10.17219/acem/121934 -
JAMA Network Open Feb 2020High levels of antimicrobial resistance in neonatal bloodstream isolates are being reported globally, including in Asia. Local hospital antibiogram data may include too...
IMPORTANCE
High levels of antimicrobial resistance in neonatal bloodstream isolates are being reported globally, including in Asia. Local hospital antibiogram data may include too few isolates to meaningfully examine the expected coverage of antibiotic regimens.
OBJECTIVE
To assess the coverage offered by 3 antibiotic regimens for empirical treatment of neonatal sepsis in Asian countries.
DESIGN, SETTING, AND PARTICIPANTS
A decision analytical model was used to estimate coverage of 3 prespecified antibiotic regimens according to a weighted-incidence syndromic combination antibiogram. Relevant data to parameterize the models were identified from a systematic search of Ovid MEDLINE and Embase. Data from Asian countries published from 2014 onward were of interest. Only data on blood culture isolates from neonates with sepsis, bloodstream infection, or bacteremia reported from the relevant setting were included. Data analysis was performed from April 2019 to July 2019.
EXPOSURES
The prespecified regimens of interest were aminopenicillin-gentamicin, third-generation cephalosporins (cefotaxime or ceftriaxone), and meropenem. The relative incidence of different bacteria and their antimicrobial susceptibility to antibiotics relevant for determining expected concordance with these regimens were extracted.
MAIN OUTCOMES AND MEASURES
Coverage was calculated on the basis of a decision-tree model incorporating relative bacterial incidence and antimicrobial susceptibility of relevant isolates. Data on 7 bacteria most commonly reported in the included studies were used for estimating coverage, which was reported at the country level.
RESULTS
Data from 48 studies reporting on 10 countries and 8376 isolates were used. Individual countries reported 51 (Vietnam) to 6284 (India) isolates. Coverage varied considerably between countries. Meropenem was generally estimated to provide the highest coverage, ranging from 64.0% (95% credible interval [CrI], 62.6%-65.4%) in India to 90.6% (95% CrI, 86.2%-94.4%) in Cambodia, followed by aminopenicillin-gentamicin (from 35.9% [95% CrI, 27.7%-44.0%] in Indonesia to 81.0% [95% CrI, 71.1%-89.7%] in Laos) and cefotaxime or ceftriaxone (from 17.9% [95% CrI, 11.7%-24.7%] in Indonesia to 75.0% [95% CrI, 64.8%-84.1%] in Laos). Aminopenicillin-gentamicin coverage was lower than that of meropenem in all countries except Laos (81.0%; 95% CrI, 71.1%-89.7%) and Nepal (74.3%; 95% CrI, 70.3%-78.2%), where 95% CrIs for aminopenicillin-gentamicin and meropenem were overlapping. Third-generation cephalosporin coverage was lowest of the 3 regimens in all countries. The coverage difference between aminopenicillin-gentamicin and meropenem for countries with nonoverlapping 95% CrIs ranged from -15.9% in China to -52.9% in Indonesia.
CONCLUSIONS AND RELEVANCE
This study's findings suggest that noncarbapenem antibiotic regimens may provide limited coverage for empirical treatment of neonatal sepsis in many Asian countries. Alternative regimens must be studied to limit carbapenem consumption.
Topics: Anti-Bacterial Agents; Asia; Bacteria; Clinical Decision-Making; Decision Trees; Drug Resistance, Bacterial; Drug Therapy, Combination; Gentamicins; Humans; Incidence; Infant, Newborn; Microbial Sensitivity Tests; Neonatal Sepsis; beta-Lactams
PubMed: 32049298
DOI: 10.1001/jamanetworkopen.2019.21124 -
Pathogens and Global Health Feb 2020The present study was conducted to investigate the antimicrobial susceptibility profiles of serotypes, especially fluoroquinolone-resistant strains, recovered from... (Meta-Analysis)
Meta-Analysis
The present study was conducted to investigate the antimicrobial susceptibility profiles of serotypes, especially fluoroquinolone-resistant strains, recovered from clinical samples in Iran. A full electronic search using related keywords was conducted in Persian and English languages in ISI Web of Knowledge, PubMed, Scopus, Google Scholar and the Scientific Information Database (SID) search engines to find papers published between 1983 and 1 July 2019. According to the inclusion and exclusion criteria, 46 eligible articles were selected for the final analysis out of the initial 13,186 studies retrieved. The pooled prevalence of quinolone-resistant serotypes in clinical specimens in Iran was 2.9% to ciprofloxacin and 48.1% to nalidixic acid. Additional data on antibiotic resistance was as follows: 54.3% to tetracycline, 50.6% to ceftizoxime, 50.2% to streptomycin, 37.9% to ampicillin, 36.5% to kanamycin, 33.5% to trimethoprim-sulfamethoxazole, 27.2% to chloramphenicol, 19.1% to cephalothin, 8.8% to ceftriaxone, 7.6% to cefotaxime, 7.4% to aztreonam, 7.2% to gentamicin, 7% to cefepime, 6.8% to ceftazidime, 5.8% to cefixime, 2.7% to imipenem and 2.2% to meropenem. Findings of the present study showed a rising trend of resistance to the drugs of choice for the treatment of infections, i.e. ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole in Iran. However, ciprofloxacin, third-generation cephalosporins and carbapenems are still effective antibiotics especially against multi-drug resistant strains in Iran.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Iran; Salmonella; Salmonella Infections
PubMed: 32013798
DOI: 10.1080/20477724.2020.1719701 -
Medicine Jan 2020Complicated urinary tract infections (cUTI) are universal reasons for hospitalization, and highly likely to develop into sepsis or septic shock. Carbapenem antibiotics... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Complicated urinary tract infections (cUTI) are universal reasons for hospitalization, and highly likely to develop into sepsis or septic shock. Carbapenem antibiotics with potentially higher efficacy or with fewer and milder side effects have increased in popularity, but evidence is limited by a scarcity of randomized controlled trials (RCTs) comparing different carbapenem antibiotics for cUTI. Network meta-analysis is a useful tool to compare multiple treatments when there is limited or no direct evidence available.
OBJECTIVE
The aim of this study is to compare the efficacy and safety of different carbapenems with alternative antibiotics for the treatment of cUTI.
METHODS
Pubmed, Medline, CENTRAL, and Embase were searched in November 2018. Studies of cUTI patients receiving carbapenem were included. We performed network meta-analysis to estimate the risk ratio (RR) and 95% credible interval (CrI) from both direct and indirect evidence; traditional meta-analysis was also performed. Primary outcomes were clinical and microbiological treatment success.
RESULTS
A total of 19 studies and 7380 patients were included in the analysis. Doripenem (DOPM) was associated with lower clinical treatment success rates than other carbapenems. Although the efficacy of other carbapenems by RRs with 95% CrIs did not show statistical differences, the cumulative rank probability indicated that meropenem/vaborbactam (MV), ertapenem (ETPM), and biapenem (BAPM) had higher clinical and microbiological treatment success rates; imipenem/cilastatin (IC) and MV showed higher risk of adverse events (AEs).
CONCLUSIONS
MV was associated with higher treatment success rates for cUTI, especially for cUTI caused by carbapenem-resistant uropathogens, but also with higher risk of AEs. Our findings suggest MV as a first-choice treatment of carbapenem-resistant cUTI. ETPM, BAPM, and meropenem (MEPM) is another reasonable choice for cUTI empiric therapy.
Topics: Anti-Bacterial Agents; Carbapenems; Humans; Network Meta-Analysis; Urinary Tract Infections
PubMed: 31914101
DOI: 10.1097/MD.0000000000018769 -
Antimicrobial Resistance and Infection... 2019Antimicrobial resistance is an increasingly serious threat to public health, and the increased occurrence of multidrug-resistant (MDR) bacteria is a concern in both... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antimicrobial resistance is an increasingly serious threat to public health, and the increased occurrence of multidrug-resistant (MDR) bacteria is a concern in both high-income and low- and middle-income countries. The purpose of this systematic review was to identify and critically appraise current antimicrobial treatment options for infections with MDR Gram-negative bacteria.
METHODS
A literature search for treatment of MDR extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, and was conducted in MEDLINE in January 2019. Relevant studies published in English, German, and French that evaluated clinical success, microbiological success, and 30-day mortality outcomes were included. The population of interest was adult patients.
RESULTS
Of 672 studies, 43 met the inclusion criteria. Carbapenems are the most common antibiotics used for the treatment of ESBL-producing Enterobacteriaceae The clinical and microbiological success was similar for group 1 carbapenems (imipenem, meropenem, or doripenem), group 2 carbapenems (ertapenem), and non-carbapenem antibiotics. Mortality data were contradictory for group 1 carbapenems compared to group 2 carbapenems. The most common treatment option for and infections was intravenous colistin, regardless of infection site. Clinical success and mortality were similar in infections treated with colistin combination therapy vs. colistin monotherapy, whereas heterogeneous results were found with respect to microbiological success. Monotherapy and colistin combination therapy were used against with clinical and microbiological success (70-100%) depending on the infection site and severity, and the antibiotic used. Ceftazidime-avibactam therapy for ESBL-producing Enterobacteriaceae and showed good clinical success in one study.
CONCLUSION
We did not find robust evidence for antibiotic treatment of any infection with MDR Gram-negative bacteria, including ESBL-producing Enterobacteriaceae, and that would lead to a firm recommendation for one specific antibiotic over another or for monotherapy over combination therapy. The choice of antibiotic treatment should be based on susceptibility testing balancing the expected clinical success rate against the risk of development of antibiotic resistance and the risk of severe side effects.
Topics: Anti-Bacterial Agents; Clinical Decision-Making; Disease Management; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Prognosis; Publication Bias; Treatment Outcome; beta-Lactamases
PubMed: 31709047
DOI: 10.1186/s13756-019-0624-1 -
Medicine Oct 2019Complicated intra-abdominal infections (cIAIs) are common in clinical practice, caused by a mixture of aerobic and anaerobic bacteria, increase the risk of mortality.... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Complicated intra-abdominal infections (cIAIs) are common in clinical practice, caused by a mixture of aerobic and anaerobic bacteria, increase the risk of mortality. Carbapenems and tigecycline (TGC) are recommended for antimicrobial therapies for cIAIs.
OBJECTIVE
To compare the effectiveness and safety of different carbapenems vs TGC for the treatment of cIAIs.
METHODS
PubMed, Embase, Medline (via Ovid SP) and Cochrane library databases were systematically searched. We included randomized controlled trials (RCTs) comparing different carbapenems vs TGC for the treatment of cIAIs. The pooled odds ratio (OR) with 95% credible interval (CrI) was calculated by Markov chain Monte Carlo methods. We estimated summary ORs using pairwise and network meta-analysis with random effects.
RESULTS
Fifteen studies involving 6745 participants were included in the analysis. Five different carbapenems and TGC were ultimately evaluated in this study. Although, the efficacy of carbapenems and TGC by ORs with corresponding 95% CrIs had not yet reached statistical differences, the cumulative rank probability indicated that clinical treatment success from best to worst was doripenem (DOPM), meropenem (MEPM), imipenem/cilastatin (IC), biapenem (BAPM), TGC and imipenem/cilastatin/relebactam (ICRB); microbiological treatment success from best to worst was DOPM, MEPM, IC, BAPM, ICRB and TGC. As for the risk of adverse events (AEs), TGC showed higher risk of AEs compared with IC (OR = 1.53, 95% CrI = 1.02-2.41), the remain antibiotic agents from lower to higher was MEPM, IC, BAPM, DOPM, ICRB and TGC. The risk of mortality from lower to higher was BAPM, DOPM, MEPM, IC, TGC and ICRB.
CONCLUSION
No differences in clinical and microbiological outcomes were observed between different carbapenems and TGC. Balancing the evidence for drug efficacy and side effects, DOPM appears to be the best available treatment for cIAIs. Therefore, it is reasonable to consider that DOPM is one of the best carbapenem monotherapy for cIAIs. MEPM and IC was also associated with higher rates of clinical and microbiological treatment success following DOPM. Empiric antimicrobial treatment of patients with cIAIs should be selected in light of the local bacterial epidemiology and patterns of resistance.
Topics: Anti-Bacterial Agents; Bayes Theorem; Carbapenems; Humans; Intraabdominal Infections; Network Meta-Analysis; Tigecycline
PubMed: 31577763
DOI: 10.1097/MD.0000000000017436