Network meta-analysis of antibiotic prophylaxis for prevention of surgical-site infection after groin hernia surgery.
ABSTRACT: First-generation cephalosporins (such as cefazolin) are recommended as antibiotic prophylaxis in groin hernia repair, but other broad-spectrum antibiotics have also been prescribed in clinical practice. This was a systematic review and network meta-analysis to compare the efficacy of different antibiotic classes for prevention of surgical-site infection (SSI) after hernia repair.RCTs were identified that compared efficacy of antibiotic prophylaxis on SSI after inguinal or femoral hernia repair from PubMed and Scopus databases up to March 2016. Data were extracted independently by two reviewers. Network meta-analysis was applied to assess treatment efficacy. The probability of being the best antibiotic prophylaxis was estimated using surface under the cumulative ranking curve (SUCRA) analysis.Fifteen RCTs (5159 patients) met the inclusion criteria. Interventions were first-generation (7 RCTs, 1237 patients) and second-generation (2 RCTs, 532) cephalosporins, ?-lactam/?-lactamase inhibitors (6 RCTs, 619) and fluoroquinolones (2 RCTs, 581), with placebo as the most common comparator (14 RCTs, 2190). A network meta-analysis showed that ?-lactam/?-lactamase inhibitors and first-generation cephalosporins were significantly superior to placebo, with a pooled risk ratio of 0·44 (95 per cent c.i. 0·25 to 0·75) and 0·62 (0·42 to 0·92) respectively. However, none of the antibiotic classes was significantly different from the others. SUCRA results indicated that ?-lactam/?-lactamase inhibitors and first-generation cephalosporins were ranked first and second respectively for best prophylaxis.?-Lactam/?-lactamase inhibitors followed by first-generation cephalosporins ranked as the most effective SSI prophylaxis for adult patients undergoing groin hernia repair.
Project description:Surgical-site infection (SSI) is a potentially serious complication following colorectal surgery. The present systematic review and meta-analysis aimed to investigate the effect of preoperative oral antibiotics and mechanical bowel preparation (MBP) on SSI rates.A systematic review of PubMed, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials was performed using appropriate keywords. Included were RCTs and observational studies reporting rates of SSI following elective colorectal surgery, in patients given preoperative oral antibiotic prophylaxis, in combination with intravenous (i.v.) antibiotic prophylaxis and MBP, compared with patients given only i.v. antibiotic prophylaxis with MBP. A meta-analysis was undertaken.Twenty-two studies (57 207 patients) were included, of which 14 were RCTs and eight observational studies. Preoperative oral antibiotics, in combination with i.v. antibiotics and MBP, were associated with significantly lower rates of SSI than combined i.v. antibiotics and MBP in RCTs (odds ratio (OR) 0·45, 95 per cent c.i. 0·34 to 0·59; P < 0·001) and cohort studies (OR 0·47, 0·44 to 0·50; P < 0·001). There was a similarly significant effect on SSI with use of a combination of preoperative oral aminoglycoside and erythromycin (OR 0·40, 0·25 to 0·64; P < 0·001), or preoperative oral aminoglycoside and metronidazole (OR 0·51, 0·39 to 0·68; P < 0·001). Preoperative oral antibiotics were significantly associated with reduced postoperative rates of anastomotic leak, ileus, reoperation, readmission and mortality in the cohort studies.Oral antibiotic prophylaxis, in combination with MBP and i.v. antibiotics, is superior to MBP and i.v. antibiotic prophylaxis alone in reducing SSI in elective colorectal surgery.
Project description:Surgical-site infections (SSIs) increase the length of hospital admission and costs. SSI prevention guidelines include preoperative antibiotic prophylaxis. This review assessed the reporting quality and cost-effectiveness of preoperative antibiotics used to prevent SSI.PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Index of Economic Articles (EconLit), Database of Abstracts of Reviews of Effect (including the National Health Service Economic Evaluation Database) and Cochrane Central databases were searched systematically from 1970 to 2017 for articles that included costs, preoperative antibiotic prophylaxis and SSI. Included were RCTs and quasi-experimental studies conducted in Organisation for Economic Co-operation and Development countries with participants aged at least 18?years and published in English. Two reviewers assessed eligibility, with inter-rater reliability determined by Cohen's ? statistic. The Consolidated Health Economic Evaluation and Reporting Standards (CHEERS) and modified Drummond checklists were used to assess reporting and economic quality. Study outcomes and characteristics were extracted, and incremental cost-effectiveness ratios were calculated, with costs adjusted to euros (2016) (€1?=?US $1·25; £1 sterling?=?€1·28).Twelve studies published between 1988 and 2014 were included from 646 records identified; nine were RCTs, two were nested within RCTs and one was a retrospective chart review. Study quality was highest in the nested studies. Cephalosporins (first, second and third generation) were the most frequent prophylactic interventions. Eleven studies demonstrated clinically effective interventions; ten were cost-effective (the intervention was dominant); in one the intervention was dominated by the control; and in one the intervention was more effective and more expensive than the control.Preoperative antibiotic prophylaxis does reduce SSI, costs to hospitals and health providers, but the reporting of economic methods in RCTs is not standardized. Routinely nesting economic methods in RCTs would improve economic evaluations and ensure appropriate selection of prophylactic antibiotics.
Project description:The consumption of antibiotics is a major driver in the development of antimicrobial resistance. This study aims to identify the trends and patterns of the total antibiotic consumption in China's tertiary hospitals from 2011 to 2015 by retrospectively analyzing aggregated monthly surveillance data on antibiotic sales made to 468 hospitals from 28 provinces. Antibiotic consumption was expressed in DDD per 1,000 inhabitants per day (DID). We compared population weighted antibiotic consumption patterns in China with European countries using indicators from the European Surveillance of Antimicrobial Consumption (ESAC). Total antibiotic consumption, including all the specific antibiotic class except for aminoglycoside antibacterials, were significantly increased during the study period from an average of 7.97 DID in 2011 to 10.08 DID in 2015. In 2015, the eastern regions of China consumed the most antibiotics using population denominator while the western regions consumed the most using inpatient denominator. Cephalosporins accounted for 28.6% of total DID, followed by beta-lactam-beta-lactamase inhibitor combinations (20.0%), macrolides (17.4%), and fluoroquinolones (10.5%). Antibiotic in parenteral form accounted for nearly half of all antibiotics. Although over the past few years major efforts had been made to reduce the risks of excessive antibiotic use through antibiotic stewardship, total antibiotic consumption showed a significant upward trend during the study period. A consistent preference for cephalosporins, macrolides, beta-lactam-beta-lactamase inhibitor combinations, as well as parenteral preparations was observed.
Project description:BACKGROUND:The application of antibiotic prophylaxis for hepatectomy remains uncertain. This research aims to evaluate different antibiotic prophylaxis strategies for hepatectomy based on network meta-analysis. METHODS:Literature retrieval was conducted in globally recognized databases, namely, MEDLINE, EMBASE and Cochrane Central, to address relative randomized controlled trials (RCTs) investigating antibiotic prophylaxis strategies for hepatectomy. Relative parametric data, including surgical site infection (SSI), remote site infection (RSI) and total infection (TI), were quantitatively pooled and estimated based on the Bayesian theorem. The values of surface under the cumulative ranking curve (SUCRA) probabilities regarding each parameter were calculated and ranked. Node-splitting analysis was performed to test the inconsistency of the main results, and publication bias was assessed by examining the funnel plot symmetry. Additional pairwise meta-analyses were performed to validate the differences between respective strategies at the statistical level. RESULTS:After a detailed review, a total of 5 RCTs containing 4 different strategies were included for the network meta-analysis. The results indicated that the application of no antibiotics possessed the highest possibility of having the best clinical effects on SSI (SUCRA, 0.56), RSI (SUCRA, 0.46) and TI (SUCRA, 0.61). Moreover, node-splitting analysis and funnel plot symmetries illustrated no inconsistencies in the current study. Additional pairwise meta-analyses determined that additional and long-duration applications had no clinical benefit. CONCLUSION:Based on current evidence, we concluded that antibiotic prophylaxis did not reveal clinical benefit in hepatectomy. However, more relative trials and statistical evidence are still needed.
Project description:BACKGROUND/AIMS:This study was performed to evaluate trends in antibiotic usage at a tertiary care hospital in Korea. METHODS:This study collated antibiotic prescription data and total patient days for inpatients at a tertiary care hospital in Korea between 2004 and 2013. The consumption of each class of antibiotic was converted to defined daily dose (DDD)/1,000 patient-days. We defined 3rd generation cephalosporins, 4th generation cephalosporins, ?-lactam/?-lactamase inhibitors, and fluoroquinolones as broad-spectrum antibiotics; carbapenems, tigecycline, glycopeptides, oxazolidinone, and polymyxin were defined as antibiotics against multidrug-resistant (MDR) pathogens. Other antibiotic classes were defined as nonbroad-spectrum antibiotics. RESULTS:Mean antibiotic consumption was 920.69 DDD/1,000 patient-days. The proportions of broad-spectrum antibiotics, antibiotics against MDR pathogens, and nonbroad-spectrum antibiotics were 41.8% (384.48/920.69), 3.5% (32.24/920.69), and 54.7% (503.97/920.69), respectively. Consumption of broad-spectrum antibiotics (coefficient for time 0.141; p = 0.049) and antibiotics against MDR pathogens (coefficient for time 0.185; p < 0.001) showed a significant increasing trend over the study period. Nonbroad-spectrum antibiotic consumption showed a significant decreasing trend over the study period (coefficient for time -2.601; p < 0.001). CONCLUSION:Over the 10-year period, a stepwise increase in the consumption of broad-spectrum antibiotics and antibiotics against MDR pathogens was observed at a tertiary care hospital in Korea. Conversely, during the same period, nonbroad-spectrum antibiotic consumption showed a significant decreasing trend.
Project description:Since the introduction of penicillin, beta-lactam antibiotics have been the antimicrobial agents of choice. Unfortunately, the efficacy of these life-saving antibiotics is significantly threatened by bacterial beta-lactamases. beta-Lactamases are now responsible for resistance to penicillins, extended-spectrum cephalosporins, monobactams, and carbapenems. In order to overcome beta-lactamase-mediated resistance, beta-lactamase inhibitors (clavulanate, sulbactam, and tazobactam) were introduced into clinical practice. These inhibitors greatly enhance the efficacy of their partner beta-lactams (amoxicillin, ampicillin, piperacillin, and ticarcillin) in the treatment of serious Enterobacteriaceae and penicillin-resistant staphylococcal infections. However, selective pressure from excess antibiotic use accelerated the emergence of resistance to beta-lactam-beta-lactamase inhibitor combinations. Furthermore, the prevalence of clinically relevant beta-lactamases from other classes that are resistant to inhibition is rapidly increasing. There is an urgent need for effective inhibitors that can restore the activity of beta-lactams. Here, we review the catalytic mechanisms of each beta-lactamase class. We then discuss approaches for circumventing beta-lactamase-mediated resistance, including properties and characteristics of mechanism-based inactivators. We next highlight the mechanisms of action and salient clinical and microbiological features of beta-lactamase inhibitors. We also emphasize their therapeutic applications. We close by focusing on novel compounds and the chemical features of these agents that may contribute to a "second generation" of inhibitors. The goal for the next 3 decades will be to design inhibitors that will be effective for more than a single class of beta-lactamases.
Project description:The identification of pathogens directly from blood cultures by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) can be a valuable tool for improving the treatment of patients with sepsis and bacteremia. However, the increasing incidence of multidrug-resistant Gram-negative bacteria makes it difficult to predict resistance patterns based only on pathogen identification. Most therapy regimens for sepsis caused by Gram-negative rods consist of at least one ?-lactam antibiotic. Thus, it would be of great benefit to have an early marker of resistance against these drugs. In the current study, we tested 100 consecutive blood cultures containing Enterobacteriaceae for resistance against 3rd-generation cephalosporins in a MALDI-TOF MS ?-lactamase assay. Escherichia coli was also tested for resistance against aminopenicillins. The results of the ?-lactamase assay were compared with those of conventional methods. The assay permitted discrimination between E. coli strains that were resistant or susceptible to aminopenicillins with a sensitivity and a specificity of 100%. The same was true for resistance to 3rd-generation cephalosporins in Enterobacteriaceae that constitutively produced class C ?-lactamases. Discrimination was more difficult in species expressing class A ?-lactamases, as these enzymes can generate false-positive results. Thus, the sensitivity and specificity for this group were 100% and 91.5%, respectively. The test permitted the prediction of resistance within 2.5 h after the blood culture was flagged as positive.
Project description:A beta-lactamase gene (cfxA3, 966 bp) was isolated from a beta-lactam-resistant Capnocytophaga ochracea clinical isolate and amplified using primers from the cfxA gene of Bacteroides vulgatus. The MICs of third-generation cephalosporins were much higher than those of the transconjugant Escherichia coli strain. The deduced protein sequence, by comparison with CfxA2 of Prevotella intermedia, had a Y239D substitution and possessed the characteristics of a class A, group 2e beta-lactamase.
Project description:Surgical site infection (SSI) is a common and preventable complication of surgery, but the relative importance of individual measures recommended by guidelines has not been determined. Elective general surgical, neurological, and orthopedic procedures requiring antibiotic prophylaxis from a 3-month period were retrospectively studied to determine concordance with SSI prevention guidelines and to identify factors which predicted the development of SSIs. A total of 216 surgeries were reviewed, with 18 SSIs (8.3%). A mean of 1.4 antibiotic prophylaxis errors per surgery were identified, with correct antibiotic type identified for 64%, antibiotic timing for 83%, supplemental antibiotic dosing for 34%, and antibiotic duration of less than 24 h for 44%. Normothermia was present in 79% of surgeries, and normoglycemia was present in 17%. Univariate analysis of the SSI rate identified four significant factors. Antibiotic prophylaxis for less than 24 h postoperatively (odds ratio [OR], 0.213; 95% confidence interval [95% CI]0.060 to 0.757) and neurosurgery (OR, 0.118; 95% CI, 0.15 to 0.903) correlated with a reduced risk of SSI. The mean number of prophylaxis errors (OR, 1.6; 95% CI, 1.02 to 2.4) and a duration of surgical drainage for more than 3 days (OR, 2.679; 95% CI, 1.009 to 7.113) predicted SSI. By multivariate analysis, errors in individual antibiotic prophylaxis measures were not significantly associated with SSI; however, the presence of more than two errors was significant (OR, 4.030; 95% CI, 1.018 to 15.96). A strong correlation was identified between the degree of concordance to SSI prevention guidelines and the SSI rate (P = 0.001, Mantel-Haenszel linear-by-linear association chi-square test).
Project description:Despite 70 years of clinical use, ?-lactam antibiotics still remain at the forefront of antimicrobial chemotherapy. The major challenge to these life-saving therapeutics is the presence of bacterial enzymes (i.e., ?-lactamases) that can hydrolyze the ?-lactam bond and inactivate the antibiotic. These enzymes can be grouped into four classes (A-D). Among the most genetically diverse are the class D ?-lactamases. In this class are ?-lactamases that can inactivate the entire spectrum of ?-lactam antibiotics (penicillins, cephalosporins, and carbapenems). Class D ?-lactamases are mostly found in Gram-negative bacteria such as Pseudomonas aeruginosa , Escherichia coli , Proteus mirabilis , and Acinetobacter baumannii . The active-sites of class D ?-lactamases contain an unusual N-carboxylated lysine post-translational modification. A strongly hydrophobic active-site helps create the conditions that allow the lysine to combine with CO2, and the resulting carbamate is stabilized by a number of hydrogen bonds. The carboxy-lysine plays a symmetric role in the reaction, serving as a general base to activate the serine nucleophile in the acylation reaction, and the deacylating water in the second step. There are more than 250 class D ?-lactamases described, and the full set of variants shows remarkable diversity with regard to substrate binding and turnover. Narrow-spectrum variants are most effective against the earliest generation penicillins and cephalosporins such as ampicillin and cephalothin. Extended-spectrum variants (also known as extended-spectrum ?-lactamases, ESBLs) pose a more dangerous clinical threat as they possess a small number of substitutions that allow them to bind and hydrolyze later generation cephalosporins that contain bulkier side-chain constituents (e.g., cefotaxime, ceftazidime, and cefepime). Mutations that permit this versatility seem to cluster in the area surrounding an active-site tryptophan resulting in a widened active-site to accommodate the oxyimino side-chains of these cephalosporins. More concerning are the class D ?-lactamases that hydrolyze clinically important carbapenem ?-lactam drugs (e.g., imipenem). Whereas carbapenems irreversibly acylate and inhibit narrow-spectrum ?-lactamases, class D carbapenemases are able to recruit and activate a deacylating water. The rotational orientation of the C6 hydroxyethyl group found on all carbapenem antibiotics likely plays a role in whether the deacylating water is effective or not. Inhibition of class D ?-lactamases is a current challenge. Commercially available inhibitors that are active against other classes of ?-lactamases are ineffective against class D enzymes. On the horizon are several compounds, consisting of both ?-lactam derivatives and non-?-lactams, that have the potential of providing novel leads to design new mechanism-based inactivators that are effective against the class D enzymes. Several act synergistically when given in combination with a ?-lactam antibiotic, and others show a unique mechanism of inhibition that is distinct from the traditional ?-lactamase inhibitors. These studies will bolster structure-based inhibitor design efforts to facilitate the optimization and development of these compounds as class D inactivators.