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Pathogens and Global Health Mar 2019Clostridium species are ubiquitous and associated with various diseases in animals and humans. However, there is little knowledge about the prevalence of their... (Meta-Analysis)
Meta-Analysis
Clostridium species are ubiquitous and associated with various diseases in animals and humans. However, there is little knowledge about the prevalence of their resistance to antibiotics in Iran. Therefore, the aim of this study was to determine the prevalence of antibiotic-resistant Clostridium species in Iran through a meta-analysis of eligible studies published up until December 2018. Fourteen articles on the drug resistance of Clostridium species in Iran were included in the current study following a search in PubMed, Scopus and Google Scholar databases using relevant keywords and screening based on inclusion and exclusion criteria. Antibiotic resistance rates of C. difficile to ampicillin (42.8%), ciprofloxacin (69.5%), clindamycin (84.3%), erythromycin (61.5%), gentamicin (93.5%), nalidixic acid (92.9%), tetracycline (32.5%), imipenem (39.6%), levofloxacin (93.4%), ertapenem (58.7%), piperacillin/tazobactam (56.5%), kanamycin (100%), colistin (100%), ceftazidime (76%), amikacin (76.5%), moxifloxacin (67.9%) and cefotaxime (95%) were high. In addition, resistance of C. perfringens to ampicillin (25.8%), erythromycin (32.9%), gentamicin (45.4%), nalidixic acid (52.5%), tetracycline (19.5%), penicillin (21.8%), trimethoprim-sulfamethoxazole (32.1%), amoxicillin (19.3%), imipenem (38%), cloxacillin (100%), oxacillin (45.6%), bacitracin (89.1%) and colistin (40%) was high. Metronidazole and vancomycin, as the first-line therapies, fidaxomicin, tetracyclines (except tetracycline), rifampicin and chloramphenicol can still be used for the treatment of C. difficile infections. However, the present results do not recommend the use of penicillin, bacitracin and tetracycline for the treatment of C. perfringens infections in humans and domestic animals in Iran.
Topics: Animal Diseases; Animals; Anti-Bacterial Agents; Clostridium; Clostridium Infections; Drug Resistance, Bacterial; Humans; Iran; Prevalence
PubMed: 30961444
DOI: 10.1080/20477724.2019.1603003 -
British Journal of Clinical Pharmacology Feb 2019Beta-lactam dose optimization in critical care is a current priority. We aimed to review the pharmacokinetics (PK) of three commonly used beta-lactams (amoxicillin ±...
AIMS
Beta-lactam dose optimization in critical care is a current priority. We aimed to review the pharmacokinetics (PK) of three commonly used beta-lactams (amoxicillin ± clavulanate, piperacillin-tazobactam and meropenem) to compare PK parameters reported in critically and noncritically ill neonates, children and adults, and to investigate whether allometric and maturation scaling principles could be applied to describe changes in PK parameters through life.
METHODS
A systematic review of PK studies of the three drugs was undertaken using MEDLINE and EMBASE. PK parameters and summary statistics were extracted and scaled using allometric principles to 70 kg individual for comparison. Pooled data were used to model clearance maturation and decline using a sigmoidal (Hill) function.
RESULTS
A total of 130 papers were identified. Age ranged from 29 weeks to 82 years and weight from 0.9-200 kg. PK parameters from critically ill populations were reported with wider confidence intervals than those in healthy volunteers, indicating greater PK variability in critical illness. The standard allometric size and sigmoidal maturation model adequately described increasing clearance in neonates, and a sigmoidal model was also used to describe decline in older age. Adult weight-adjusted clearance was achieved at approximately 2 years postmenstrual age. Changes in volume of distribution were well described by the standard allometric model, although amoxicillin data suggested a relatively higher volume of distribution in neonates.
CONCLUSIONS
Critical illness is associated with greater PK variability than in healthy volunteers. The maturation models presented will be useful for optimizing beta-lactam dosing, although a prospective, age-inclusive study is warranted for external validation.
Topics: Adult; Age Factors; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Infections; Biological Variation, Population; Child; Critical Illness; Dose-Response Relationship, Drug; Healthy Volunteers; Humans; Infant, Newborn; Meropenem; Microbial Sensitivity Tests; Piperacillin, Tazobactam Drug Combination; beta-Lactamase Inhibitors
PubMed: 30176176
DOI: 10.1111/bcp.13756 -
Antimicrobial Resistance and Infection... 2018Identifying risk factors predicting acquisition of resistant will aid surveillance and diagnostic initiatives and can be crucial in early and appropriate antibiotic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Identifying risk factors predicting acquisition of resistant will aid surveillance and diagnostic initiatives and can be crucial in early and appropriate antibiotic therapy. We conducted a systematic review examining risk factors of acquisition of resistant among hospitalized patients.
METHODS
MEDLINE®, EMBASE®, and Cochrane Central were searched between 2000 and 2016 for studies examining independent risk factors associated with acquisition of resistant , among hospitalized patients. Random effects model meta-analysis was conducted when at least three or more studies were sufficiently similar.
RESULTS
Of the 54 eligible articles, 28 publications (31studies) examined multi-drug resistant (MDR) or extensively drug resistant (XDR) and 26 publications (29 studies) examined resistant The acquisition of MDR , as compared with non-MDR , was significantly associated with intensive care unit (ICU) admission (3 studies: summary adjusted odds ratio [OR] 2.2) or use of quinolones (4 studies: summary adjusted OR 3.59). Acquisition of MDR or XDR compared with susceptible was significantly associated with prior hospital stay (4 studies: summary adjusted OR 1.90), use of quinolones (3 studies: summary adjusted OR 4.34), or use of carbapenems (3 studies: summary adjusted OR 13.68). The acquisition of MDR compared with non- was significantly associated with prior use of cephalosporins (3 studies: summary adjusted OR 3.96), quinolones (4 studies: summary adjusted OR 2.96), carbapenems (6 studies: summary adjusted OR 2.61), and prior hospital stay (4 studies: summary adjusted OR 1.74). The acquisition of carbapenem-resistant compared with susceptible , was statistically significantly associated with prior use of piperacillin-tazobactam (3 studies: summary adjusted OR 2.64), vancomycin (3 studies: summary adjusted OR 1.76), and carbapenems (7 studies: summary adjusted OR 4.36).
CONCLUSIONS
Prior use of antibiotics and prior hospital or ICU stay was the most significant risk factors for acquisition of resistant . These findings provide guidance in identifying patients that may be at an elevated risk for a resistant infection and emphasize the importance of antimicrobial stewardship and infection control in hospitals.
Topics: Adult; Aged; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Cephalosporins; Critical Care; Cross Infection; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Pseudomonas aeruginosa; Quinolones; Risk Factors; Vancomycin
PubMed: 29997889
DOI: 10.1186/s13756-018-0370-9 -
The Indian Journal of Medical Research Mar 2017Neonates present a special subgroup of population in whom optimization of antimicrobial dosing can be particularly challenging. Gram-negative infections are common in... (Review)
Review
BACKGROUND & OBJECTIVES
Neonates present a special subgroup of population in whom optimization of antimicrobial dosing can be particularly challenging. Gram-negative infections are common in neonates, and inpatient treatment along with critical care is needed for the management of these infections. Dosing recommendations are often extrapolated from evidence generated in older patient populations. This systematic review was done to identify the knowledge gaps in the pharmacokinetics-pharmacodynamics (PK-PD)-based optimized dosing schedule for parenteral antimicrobials for Gram-negative neonatal infections.
METHODS
Relevant research questions were identified. An extensive electronic and manual search methodology was used. Potentially eligible articles were screened for eligibility. The relevant data were extracted independently in a pre-specified data extraction form. Pooling of data was planned.
RESULTS
Of the 340 records screened, 24 studies were included for data extraction and incorporation in the review [carbapenems - imipenem and meropenem (n=7); aminoglycosides - amikacin and gentamicin (n=9); piperacillin-tazobactam (n=2); quinolones (n=2); third- and fourth-generation cephalosporins (n=4) and colistin nil]. For each of the drug categories, the information for all the questions that the review sought to answer was incomplete. There was a wide variability in the covariates assessed, and pooling of results could not be undertaken.
INTERPRETATION & CONCLUSIONS
There is a wide knowledge gap for determining the doses of antimicrobials used for Gram-negative infections in neonates. A different profile of newborns in the developing countries could affect the disposition of antimicrobials for Gram negative infections, necessitating the generation of PK-PD data of antimicrobials in neonates from developing countries. Further, guidelines for treatment of neonatal conditions may incorporate the evidence-based PK-PD-guided dosing regimens.
Topics: Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Infant, Newborn; Microbial Sensitivity Tests; Pseudomonas aeruginosa
PubMed: 28749392
DOI: 10.4103/ijmr.IJMR_723_15 -
Clinical Microbiology and Infection :... Oct 2017To compare the effectiveness and safety of antipseudomonal β-lactam empiric monotherapy for febrile neutropenia by network meta-analysis. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVES
To compare the effectiveness and safety of antipseudomonal β-lactam empiric monotherapy for febrile neutropenia by network meta-analysis.
METHODS
Searches using Pubmed, Cochrane CENTRAL, EMBASE and Web of Science Core Collection were carried out in June 2016. English articles, non-English articles, full-length articles, short articles and conference abstracts were allowed. Eligible trial design was a parallel-group individual randomization. We included febrile neutropenia adult and paediatric patients undergoing chemotherapy for either solid tumours or haematological malignancies and treated with intravenous antipseudomonal β-lactams for initial empiric therapy. Protocol was registered with PROSPERO ID 42016043377.
RESULTS
Of 1275 articles detected by the search, 50 studies with 10 872 patients were finally included. Among the guideline-recommended cefepime, meropenem, imipenem/cilastatin, piperacillin/tazobactam and ceftazidime; imipenem/cilastatin showed the highest odds of treatment success without modification, which was the primary endpoint, based on the random-effect model network analysis. Ceftazidime was related to lower treatment success rate without modification compared with imipenem/cilastatin with OR of 0.71 (95% CI 0.57-0.89, p 0.006). Imipenem/cilastatin showed the lowest odds of all-cause death. Patients treated with cefepime had higher risk for all-cause death compared with those treated with imipenem/cilastatin (OR 2.05, 95% CI 1.11-3.78, p 0.029). Any adverse event was significantly more prevalent in the imipenem/cilastatin arm; however, there was no difference concerning adverse events leading to discontinuation.
CONCLUSIONS
Imipenem/cilastatin, piperacillin/tazobactam and meropenem may be reasonable first-choice medications for empiric therapy of febrile neutropenia.
Topics: Anti-Bacterial Agents; Drug-Related Side Effects and Adverse Reactions; Febrile Neutropenia; Humans; Neoplasms; Survival Analysis; Treatment Outcome; beta-Lactams
PubMed: 28377312
DOI: 10.1016/j.cmi.2017.03.024 -
Scientific Reports Nov 2016It has been widely reported that the incidence and severity of Clostridium difficile infection (CDI) have increased dramatically in North America and Europe. However,... (Meta-Analysis)
Meta-Analysis Review
It has been widely reported that the incidence and severity of Clostridium difficile infection (CDI) have increased dramatically in North America and Europe. However, little is known about CDI in Mainland China. In this study, we aimed to investigate the incidence of CDI and the main epidemic and drug-resistant strains of C. difficile in Mainland China through meta-analysis of related studies published after the year 2010. A total of 51 eligible studies were included. The pooled incidence of toxigenic C. difficile among patients with diarrhoea was 14% (95% CI = 12-16%). In Mainland China, ST-37 and ST-3 were the most prevalent strains; fortunately, hypervirulent strains, such as ST-1 (BI/NAP1/027) and ST-11 (RT 078), have only occurred sporadically to date. The rates of C. difficile resistance to ciprofloxacin (98.3%; 95% CI = 96.9-99.7%), clindamycin (81.7%; 95% CI = 76.1-87.3%) and erythromycin (80.2%; 95% CI = 73.5-86.9%) are higher than in other counties; however, none of the C. difficile isolates reported in Mainland China were resistant to metronidazole (n/N = 0/960), vancomycin (n/N = 0/960), tigecycline (n/N = 0/41) or piperacillin/tazobactam(n/N = 0/288).
Topics: Anti-Bacterial Agents; China; Ciprofloxacin; Clindamycin; Clostridioides difficile; Clostridium Infections; Drug Resistance, Bacterial; Erythromycin; Female; Humans; Incidence; Male; Microbial Sensitivity Tests
PubMed: 27897206
DOI: 10.1038/srep37865 -
Journal of Pharmacy & Pharmaceutical... 2016A better dosing strategy can improve clinical outcomes for patients. We systematically reviewed the literatures to determine whether any clinical benefits exist for... (Meta-Analysis)
Meta-Analysis Review
A better dosing strategy can improve clinical outcomes for patients. We systematically reviewed the literatures to determine whether any clinical benefits exist for piperacillin/tazobactam by extended or continuous infusion. Methods - A search of PubMed, Web of Science, ProQuest, ScienceDirect, Cochrane, Embase and related ICAAC and ACCP conferences were conducted up to September 5, 2015. Randomized controlled and observational studies that compared extended or continuous infusion with conventional intermittent infusion of piperacillin/tazobactam were identified from the databases above and analyzed. Two reviewers independently evaluated the methodology and extracted data from primary studies. A meta-analysis was performed using Revman 5.2 software. The quality of each study was assessed. Sensitivity analysis and publication bias were evaluated. Results - Three randomized controlled trials and twelve observational studies were included in this study. All included studies had high quality and no publication bias was found. Compared to the conventional intermittent infusion approach, the extended or continuous infusion group had a significant cost effectiveness (OR -0.89.02, CI (-114.69,-63.35), P<0.00001). No statistical difference was observed for clinical cure rate (OR 1.64, 95% CI (0.88, 3.30), P=0.12) between the two dosing regimens. The sensitivity analysis showed the results were stable. Conclusions - Our systematic review and meta-analysis found that the outcomes associated with alternative dosing strategies of piperacillin/tazobactam have changed compared with conclusions before for several literatures with large samples published. Further data on the outcomes should be generated for a better understanding of the extended or continuous infusion strategy. On the whole, our meta-analysis suggested that the extended or continuous infusion should be recommended for clinical use only considering its economic advantage, but there was no significantly higher clinical cure rate and lower mortality rate compared with the conventional intermittent infusion. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Administration Schedule; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tazobactam; Treatment Outcome
PubMed: 27518175
DOI: 10.18433/jpps.v19i2.27517 -
BMC Infectious Diseases Dec 2015Healthcare-associated infections (HCAI) represent up to 50 % of all infections among patients admitted from the community. The current review intends to provide a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Healthcare-associated infections (HCAI) represent up to 50 % of all infections among patients admitted from the community. The current review intends to provide a systematic review on the microbiological profile involved in HCAI, to compare it with community-acquired (CAI) and hospital-acquired infections (HAI) and to evaluate the definition accuracy to predict infection by potentially drug resistant pathogens.
METHODS
We search for HCAI in MEDLINE, SCOPUS and ISI Web of Knowledge with no limitations in regards to publication language, date of publication, study design or study quality. Only studies using the definition by Friedman et al. were included. This review was registered at PROSPERO Systematic Review Registration with the Number CRD42014013648.
RESULTS
A total of 21 eligible studies with 12,096 infected patients were reviewed; of these 3497 had HCAI, 2723 were microbiologically documented. Twelve studies were on pneumonia involving 1051 patients with microbiological documented HCAI, the application of the current guidelines for this group of patients would result in an appropriate antibiotic therapy in 95 % of cases at the expense of overtreatment in 73 %; the application of community-acquired pneumonia guidelines would be adequate in only 73-76 % of the cases; an alternative regimen with piperacillin-tazobactam or aztreonam plus azithromycin would increase antibiotic adequacy rate to 90 %. Few studies were found on additional focus of infection: endocarditis, urinary, intra-abdominal and bloodstream infections. All studies included in this review showed an association of the HCAI definition with infection by PDR pathogens when compared to CAI [odds ratio (OR) 4.05, 95 % confidence interval (95 % CI) 2.60-6.31)]. The sensitivity of HCAI to predict infection by a PDR pathogen was 0.69 (0.65-0.72), specificity was 0.67 (0.66-0.68), positive likelihood ratio was 1.9 and the area under the summary ROC curve was 0.71.
CONCLUSIONS
This systematic review provides evidence that HCAI represents a separate group of infections in terms of the microbiology profile, including a significant association with infection by PDR pathogens, for the main focus of infection. The results provided can help clinician in the selection of empiric antibiotic therapy and international societies in the development of specific treatment recommendations.
Topics: Anti-Bacterial Agents; Area Under Curve; Bacteria; Community-Acquired Infections; Cross Infection; Databases, Factual; Drug Resistance, Multiple, Bacterial; Humans; Odds Ratio; Pneumonia; ROC Curve
PubMed: 26653533
DOI: 10.1186/s12879-015-1304-2 -
BMC Infectious Diseases Aug 2015Empiric therapy for healthcare-associated infections remains challenging, especially with the continued development of Gram-negative organisms producing... (Review)
Review
Empiric therapy for hospital-acquired, Gram-negative complicated intra-abdominal infection and complicated urinary tract infections: a systematic literature review of current and emerging treatment options.
BACKGROUND
Empiric therapy for healthcare-associated infections remains challenging, especially with the continued development of Gram-negative organisms producing extended-spectrum β-lactamases (ESBLs) and the threat of multi-drug-resistant organisms. Current treatment options for resistant Gram-negative infections include carbapenems, tigecycline, piperacillin-tazobactam, cefepime, ceftazidime, and two recently approved therapies, ceftolozane-tazobactam and ceftazidime-avibactam.
METHODS
This systematic literature review surveys the published clinical trial evidence available since 2000 in support of both current and emerging treatment options in the settings of complicated intra-abdominal infection (cIAI) and complicated urinary tract infection (cUTI). When available, clinical cure rates for patients with infections from ESBL-producing strains are provided, as is information about efficacy against Pseudomonas aeruginosa.
RESULTS
Clinical trial evidence to guide selection of empiric antibiotic therapy in patients with complicated, hospital-acquired, Gram-negative IAIs and UTIs is limited. Though most of the clinical trials explored in this overview enrolled patients with complicated infections, often patients with severe infections and multiple comorbidities were excluded.
CONCLUSIONS
Practitioners in the clinical setting who are treating patients with complicated, hospital-acquired, Gram-negative IAIs and UTIs need to consider the possibility of polymicrobial infections, antibiotic-resistant organisms, and/or severely ill patients with multiple comorbidities. There is a severe shortage of evidence-based research to guide the selection of empiric antibiotic therapy for many patients in this setting. New therapies recently approved or in late-stage development promise to expand the number of options available for empiric therapy of these hospital-acquired, Gram-negative infections.
Topics: Anti-Bacterial Agents; Databases, Factual; Gram-Negative Bacterial Infections; Humans; Intraabdominal Infections; Treatment Outcome; Urinary Tract Infections
PubMed: 26243291
DOI: 10.1186/s12879-015-1054-1 -
PloS One 2015A better dosing strategy can improve clinical outcomes for patients. We sought to compare the extended or continuous infusion with conventional intermittent infusion of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
A better dosing strategy can improve clinical outcomes for patients. We sought to compare the extended or continuous infusion with conventional intermittent infusion of piperacillin/tazobactam, investigating which approach is better and worthy of recommendation for clinical use.
METHODS
Articles were gathered from PubMed, Web of Science, ProQuest, Science Direct, Cochrane, two Chinese literature databases (CNKI, Wan Fang Data) and related ICAAC and ACCP conferences. Randomized controlled and observational studies that compared extended or continuous infusion with conventional intermittent infusion of piperacillin/tazobactam were identified from the databases above and analyzed. Two reviewers independently extracted and investigated the data. A meta-analysis was performed using Revman 5.2 software. The quality of each study was assessed. Sensitivity analysis and publication bias were evaluated.
RESULTS
Five randomized controlled trials and nine observational studies were included in this study. All included studies had high quality and no publication bias was found. Compared to the conventional intermittent infusion approach, the extended or continuous infusion group had a significantly higher clinical cure rate (OR 1.88, 95% CI 1.29-2.73, P = 0.0009) and a lower mortality rate (OR 0.67, 95% CI 0.50-0.89, P = 0.005). No statistical difference was observed for bacteriologic cure (OR 1.40, 95% CI 0.82-2.37, P = 0.22) between the two dosing regimens. The sensitivity analysis showed the results were stable.
CONCLUSIONS
Our systematic review and meta-analysis suggested that the extended or continuous infusion strategy of piperacillin/tazobactam should be recommended for clinical use considering its higher clinical cure rate and lower mortality rate in comparison with conventional intermittent strategy. Data from this study could be extrapolated for other β-lactam antimicrobials. Therefore, this dosing strategy could be considered in clinical practice.
Topics: Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Databases, Factual; Humans; Odds Ratio; Penicillanic Acid; Piperacillin; Renal Insufficiency; Tachycardia; Tazobactam
PubMed: 25575030
DOI: 10.1371/journal.pone.0116769