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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 -
Clinical Infectious Diseases : An... Nov 2022Therapeutic drug monitoring (TDM) of beta-lactam antibiotics is recommended to address the variability in exposure observed in critical illness. However, the impact of... (Meta-Analysis)
Meta-Analysis
Therapeutic drug monitoring (TDM) of beta-lactam antibiotics is recommended to address the variability in exposure observed in critical illness. However, the impact of TDM-guided dosing on clinical outcomes remains unknown. We conducted a systematic review and meta-analysis on TDM-guided dosing and clinical outcomes (all-cause mortality, clinical cure, microbiological cure, treatment failure, hospital and intensive care unit length of stay, target attainment, antibiotic-related adverse events, and emergence of resistance) in critically ill patients with suspected or proven sepsis. Eleven studies (n = 1463 participants) were included. TDM-guided dosing was associated with improved clinical cure (relative risk, 1.17; 95% confidence interval [CI], 1.04 to 1.31), microbiological cure (RR, 1.14; 95% CI, 1.03 to 1.27), treatment failure (RR, 0.79; 95% CI, .66 to .94), and target attainment (RR, 1.85; 95% CI, 1.08 to 3.16). No associations with mortality and length of stay were found. TDM-guided dosing improved clinical and microbiological cure and treatment response. Larger, prospective, randomized trials are required to better assess the utility of beta-lactam TDM in critically ill patients.
Topics: Humans; Critical Illness; Drug Monitoring; Prospective Studies; beta-Lactams; Anti-Bacterial Agents; Monobactams
PubMed: 35731853
DOI: 10.1093/cid/ciac506 -
PloS One 2020The association between sodium-glucose cotransporter 2 inhibitors (SGLT2i's) and lower extremity amputation is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The association between sodium-glucose cotransporter 2 inhibitors (SGLT2i's) and lower extremity amputation is unclear.
PURPOSE
To systematically review randomized control trials (RCTs) and observational studies quantifying risk of lower extremity amputations associated with SGLT2i use.
DATA SOURCES AND STUDY SELECTION
We searched PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from January 2011 to February 2020 for RCTs and observational studies including lower extremity amputation outcomes for individuals with type 2 diabetes mellitus treated with SGLT2i's vs. alternative treatments or placebo.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data.
MAIN OUTCOMES AND MEASURES
Our primary outcome was risk of lower limb amputation. Secondary outcomes included peripheral arterial disease, peripheral vascular disease, venous ulcerations, and diabetic foot infections. We also evaluated the risk of bias. We conducted random and fixed effects relative risk meta-analysis of RCTs.
RESULTS
After screening 2,006 studies, 12 RCTs and 18 observational studies were included, of which 7 RCTs and 18 observational studies had at least one event. The random effects meta-analysis of 7 RCTs suggested the absence of a statistically significant association between SGLT2i exposure with evidence of substantial statistical heterogeneity (n = 424/23,716 vs n = 267/18,737 in controls; RR 1.28, CI's 0.93-1.76; I2 = 62.0%; p = 0.12) whereas fixed effects analysis showed an increased risk with statistical heterogeneity (RR 1.27, 1.09-1.48; I2 = 62%; p = 0.003). Subgroup analysis of canagliflozin vs placebo showed a statistically significantly increased risk in a fixed effects meta-analysis (n = 2 RCTs, RR 1.59, 1.26-2.01; I2 = 88%; p = 0.0001) whereas the meta-analysis of dapagliflozin or empagliflozin (n = 2 RCTs each) and a single RCT for ertugliflozin did not show a significantly increased risk. The findings from observational studies were too heterogeneous to be pooled in a meta-analysis and draw meaningful conclusions. Both randomized and observational studies were of generally good methodological quality.
CONCLUSIONS
Overall, there was no consistent evidence of SGLT2i exposure and increased risk of amputation. The increased risk of amputation seen in the large, long-term Canagliflozin Cardiovascular Assessment Study (CANVAS) trial for canagliflozin, and select observational studies, merits continued exploration.
Topics: Amputation, Surgical; Benzhydryl Compounds; Glucosides; Humans; Lower Extremity; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Risk; Sodium-Glucose Transporter 2 Inhibitors; Sulfonylurea Compounds
PubMed: 32502190
DOI: 10.1371/journal.pone.0234065 -
International Journal of Environmental... Dec 2020(1) Background: There is increasing awareness that the quality of the indoor environment affects our health and well-being. Indoor air quality (IAQ) in particular has an...
(1) Background: There is increasing awareness that the quality of the indoor environment affects our health and well-being. Indoor air quality (IAQ) in particular has an impact on multiple health outcomes, including respiratory and cardiovascular illness, allergic symptoms, cancers, and premature mortality. (2) Methods: We carried out a global systematic literature review on indoor exposure to selected air pollutants associated with adverse health effects, and related household characteristics, seasonal influences and occupancy patterns. We screened records from six bibliographic databases: ABI/INFORM, Environment Abstracts, Pollution Abstracts, PubMed, ProQuest Biological and Health Professional, and Scopus. (3) Results: Information on indoor exposure levels and determinants, emission sources, and associated health effects was extracted from 141 studies from 29 countries. The most-studied pollutants were particulate matter (PM and PM); nitrogen dioxide (NO); volatile organic compounds (VOCs) including benzene, toluene, xylenes and formaldehyde; and polycyclic aromatic hydrocarbons (PAHs) including naphthalene. Identified indoor PM sources include smoking, cooking, heating, use of incense, candles, and insecticides, while cleaning, housework, presence of pets and movement of people were the main sources of coarse particles. Outdoor air is a major PM source in rooms with natural ventilation in roadside households. Major sources of NO indoors are unvented gas heaters and cookers. Predictors of indoor NO are ventilation, season, and outdoor NO levels. VOCs are emitted from a wide range of indoor and outdoor sources, including smoking, solvent use, renovations, and household products. Formaldehyde levels are higher in newer houses and in the presence of new furniture, while PAH levels are higher in smoking households. High indoor particulate matter, NO and VOC levels were typically associated with respiratory symptoms, particularly asthma symptoms in children. (4) Conclusions: Household characteristics and occupant activities play a large role in indoor exposure, particularly cigarette smoking for PM, gas appliances for NO, and household products for VOCs and PAHs. Home location near high-traffic-density roads, redecoration, and small house size contribute to high indoor air pollution. In most studies, air exchange rates are negatively associated with indoor air pollution. These findings can inform interventions aiming to improve IAQ in residential properties in a variety of settings.
Topics: Air Pollutants; Air Pollution, Indoor; Child; Humans; Particulate Matter; Polycyclic Aromatic Hydrocarbons; Volatile Organic Compounds
PubMed: 33276576
DOI: 10.3390/ijerph17238972 -
BMC Infectious Diseases Apr 2023Which antimicrobial agents provide the optimal efficacy, safety, and tolerability for the empirical treatment of complicated intra-abdominal infection (cIAI) remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Which antimicrobial agents provide the optimal efficacy, safety, and tolerability for the empirical treatment of complicated intra-abdominal infection (cIAI) remains unclear but is paramount in the context of evolving antimicrobial resistance. Therefore, updated meta-analyses on this issue are warranted.
METHODS
We systematically searched four major electronic databases from their inception through October 2022. Randomized controlled trials examining antimicrobial agents for cIAI treatment were included. Two reviewers independently assessed the quality of included studies utilizing the Cochrane Collaboration's risk of bias tool as described in the updated version 1 of the Cochrane Collaboration Handbook and extracted data from all manuscripts according to a predetermined list of topics. All meta-analyses were conducted using R software. The primary outcome was clinical success rate in patients with cIAIs.
RESULTS
Forty-five active-controlled trials with low to medium methodological quality and involving 14,267 adults with cIAIs were included in the network meta-analyses. The vast majority of patients with an acute physiology and chronic health evaluation II score < 10 had low risk of treatment failure or death. Twenty-one regimens were investigated. In the network meta-analyses, cefepime plus metronidazole was more effective than tigecycline and ceftolozane/tazobactam plus metronidazole (odds ratio [OR] = 1.96, 95% credibility interval [CrI] 1.05 ~ 3.79; OR = 3.09, 95% CrI 1.02 ~ 9.79, respectively). No statistically significant differences were found among antimicrobial agents regarding microbiological success rates. Cefepime plus metronidazole had lower risk of all-cause mortality than tigecycline (OR = 0.22, 95% CrI 0.05 ~ 0.85). Statistically significant trends were observed favoring cefotaxime plus metronidazole, which exhibited fewer discontinuations because of adverse events (AEs) when compared with eravacycline, meropenem and ceftolozane/tazobactam plus metronidazole (OR = 0.0, 95% CrI 0.0 ~ 0.8; OR = 0.0, 95% CrI 0.0 ~ 0.7; OR = 0.0, 95% CrI 0.0 ~ 0.64, respectively). Compared with tigecycline, eravacycline was associated with fewer discontinuations because of AEs (OR = 0.17, 95% CrI 0.03 ~ 0.81). Compared with meropenem, ceftazidime/avibactam plus metronidazole had a higher rate of discontinuation due to AEs (OR = 2.09, 95% CrI 1.0 ~ 4.41). In pairwise meta-analyses, compared with ceftriaxone plus metronidazole, ertapenem and moxifloxacin (one trial, OR = 1.93, 95% CI 1.06 ~ 3.50; one trial, OR = 4.24, 95% CI 1.18 ~ 15.28, respectively) were associated with significantly increased risks of serious AEs. Compared with imipenem/cilastatin, tigecycline (four trials, OR = 1.57, 95%CI 1.07 ~ 2.32) was associated with a significantly increased risk of serious AEs. According to the surface under the cumulative ranking curve, Cefepime plus metronidazole was more likely to be optimal among all treatments in terms of efficacy and safety, tigecycline was more likely to be worst regimen in terms of tolerability, and eravacycline was more likely to be best tolerated.
CONCLUSION
This study suggests that cefepime plus metronidazole is optimal for empirical treatment of patients with cIAIs and that tigecycline should be prescribed cautiously considering the safety and tolerability concerns. However, it should be noted that data currently available on the effectiveness, safety, and tolerability of antimicrobial agents pertain mostly to lower-risk patients with cIAIs.
Topics: Adult; Humans; Metronidazole; Meropenem; Network Meta-Analysis; Tigecycline; Cefepime; Anti-Bacterial Agents; Intraabdominal Infections; Tazobactam; Anti-Infective Agents
PubMed: 37085768
DOI: 10.1186/s12879-023-08209-9 -
The Cochrane Database of Systematic... Mar 2021Leg ulcers are open skin wounds that occur below the knee but above the foot. The majority of leg ulcers are venous in origin, occurring as a result of venous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Leg ulcers are open skin wounds that occur below the knee but above the foot. The majority of leg ulcers are venous in origin, occurring as a result of venous insufficiency, where the flow of blood through the veins is impaired; they commonly arise due to blood clots and varicose veins. Compression therapy, using bandages or stockings, is the primary treatment for venous leg ulcers. Wound cleansing can be used to remove surface contaminants, bacteria, dead tissue and excess wound fluid from the wound bed and surrounding skin, however, there is uncertainty regarding the effectiveness of cleansing and the best method or solution to use.
OBJECTIVES
To assess the effects of wound cleansing, wound cleansing solutions and wound cleansing techniques for treating venous leg ulcers.
SEARCH METHODS
In September 2019 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) comparing wound cleansing with no wound cleansing, or RCTs comparing different wound cleansing solutions, or different wound cleansing techniques.
DATA COLLECTION AND ANALYSIS
We screened studies for their appropriateness for inclusion, assessed their risk of bias using the Cochrane 'Risk of bias' tool, and used GRADE methodology to determine the certainty of evidence. Two review authors undertook these tasks independently, using predetermined criteria. We contacted study authors for missing data where possible.
MAIN RESULTS
We included four studies with a total of 254 participants. All studies included comparisons between different types of cleansing solutions, and three of these reported our primary outcomes of complete wound healing or change in ulcer size over time, or both. Two studies reported the secondary outcome, pain. One study (27 participants), which compared polyhexamethylene biguanide (PHMB) solution with saline solution for cleansing venous leg ulcers, did not report any of the review's primary or secondary outcomes. We did not identify any studies that compared cleansing with no cleansing, or that explored comparisons between different cleansing techniques. One study (61 participants) compared aqueous oxygen peroxide with sterile water. We are uncertain whether aqueous oxygen peroxide makes any difference to the number of wounds completely healed after 12 months of follow-up (risk ratio (RR) 1.88, 95% confidence interval (CI) 1.10 to 3.20). Similarly, we are uncertain whether aqueous oxygen peroxide makes any difference to change in ulcer size after eight weeks of follow-up (mean difference (MD) -1.38 cm, 95% CI -4.35 to 1.59 cm). Finally, we are uncertain whether aqueous oxygen peroxide makes any difference to pain reduction, assessed after eight weeks of follow-up using a 0 to 100 pain rating, (MD 3.80, 95% CI -10.83 to 18.43). The evidence for these outcomes is of very low certainty (we downgraded for study limitations and imprecision; for the pain outcome we also downgraded for indirectness). Another study (40 participants) compared propyl betaine and polihexanide with a saline solution. The authors did not present the raw data in the study report so we were unable to conduct independent statistical analysis of the data. We are uncertain whether propyl betaine and polihexanide make any difference to the number of wounds completely healed, change in ulcer size over time, or wound pain reduction. The evidence is of very low certainty (we downgraded for study limitations and imprecision). The final study (126 participants) compared octenidine dihydrochloride/phenoxyethanol (OHP) with Ringer's solution. We are uncertain whether OHP makes any difference to the number of wounds healed (RR 0.96, 95% CI 0.53 to 1.72) or to the change in ulcer size over time (we were unable to conduct independent statistical analysis of available data). The evidence is of very low certainty (we downgraded for study limitations and imprecision). None of the studies reported patient preference, ease of use of the method of cleansing, cost or health-related quality of life. In one study comparing propyl betaine and polihexanide with saline solution the authors do not report any adverse events occurring. We are uncertain whether OHP makes any difference to the number of adverse events compared with Ringer's solution (RR 0.58, 95% CI 0.29 to 1.14). The evidence is of very low certainty (we downgraded for study limitations and imprecision).
AUTHORS' CONCLUSIONS
There is currently a lack of RCT evidence to guide decision making about the effectiveness of wound cleansing compared with no cleansing and the optimal approaches to cleansing of venous leg ulcers. From the four studies identified, there is insufficient evidence to demonstrate whether the use of PHMB solution compared with saline solution; aqueous oxygen peroxide compared with sterile water; propyl betaine and polihexanide compared with a saline solution; or OHP compared with Ringer's solution makes any difference in the treatment of venous leg ulcers. Evidence from three of the studies is of very low certainty, due to study limitations and imprecision. One study did not present data for the primary or secondary outcomes. Further well-designed studies that address important clinical, quality of life and economic outcomes may be important, based on the clinical and patient priority of this uncertainty.
Topics: Aged; Anti-Infective Agents, Local; Betaine; Bias; Biguanides; Confidence Intervals; Detergents; Disinfectants; Ethylene Glycols; Female; Humans; Hydrogen Peroxide; Imines; Male; Middle Aged; Pain Measurement; Pyridines; Randomized Controlled Trials as Topic; Ringer's Solution; Saline Solution; Varicose Ulcer; Wound Healing
PubMed: 33734426
DOI: 10.1002/14651858.CD011675.pub2 -
BMC Cancer Aug 2023Patients with triple-negative breast cancer (TNBC) are generally younger and more likely to experience disease recurrence and have the shortest survival among all breast... (Meta-Analysis)
Meta-Analysis
Neoadjuvant immunotherapy and chemotherapy regimens for the treatment of high-risk, early-stage triple-negative breast cancer: a systematic review and network meta-analysis.
BACKGROUND
Patients with triple-negative breast cancer (TNBC) are generally younger and more likely to experience disease recurrence and have the shortest survival among all breast cancer patients. Recently, neoadjuvant delivery of the programmed cell death protein-1 inhibitor pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab was approved for patients with high-risk, early-stage TNBC, but this treatment regimen has not been evaluated in head-to-head trials with other neoadjuvant treatment regimens. Therefore, the objective of this study was to estimate the relative efficacy of neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab versus other neoadjuvant treatments for early-stage TNBC through a systematic review and network meta-analysis (NMA).
METHODS
EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, conference abstracts, and clinical trial registries were searched for randomized controlled trials evaluating neoadjuvant treatments for early-stage TNBC. NMA was performed to estimate relative treatment effects among evaluated interventions.
RESULTS
Five trials met the inclusion criteria and were included in the NMA. The relative efficacy of neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab was favorable to paclitaxel followed by anthracycline + cyclophosphamide in terms of pathologic complete response (pCR), event-free survival (EFS), and overall survival; paclitaxel + carboplatin followed by anthracycline + cyclophosphamide in terms of pCR and EFS; paclitaxel + bevacizumab followed by anthracycline + cyclophosphamide + bevacizumab in terms of pCR; and paclitaxel + carboplatin + veliparib followed by anthracycline + cyclophosphamide in terms of EFS.
CONCLUSIONS
Neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab confers benefits in response and survival outcomes versus alternative neoadjuvant treatments for early-stage TNBC.
Topics: Humans; Neoadjuvant Therapy; Triple Negative Breast Neoplasms; Network Meta-Analysis; Bevacizumab; Carboplatin; Neoplasm Recurrence, Local; Immunotherapy; Adjuvants, Immunologic; Anthracyclines; Cyclophosphamide; Paclitaxel
PubMed: 37612624
DOI: 10.1186/s12885-023-11293-4 -
The Cochrane Database of Systematic... Aug 2020Pelvic inflammatory disease (PID) affects 4% to 12% of women of reproductive age. The main intervention for acute PID is broad-spectrum antibiotics administered... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pelvic inflammatory disease (PID) affects 4% to 12% of women of reproductive age. The main intervention for acute PID is broad-spectrum antibiotics administered intravenously, intramuscularly or orally. We assessed the optimal treatment regimen for PID. OBJECTIVES: To assess the effectiveness and safety of antibiotic regimens to treat PID.
SEARCH METHODS
In January 2020, we searched the Cochrane Sexually Transmitted Infections Review Group's Specialized Register, which included randomized controlled trials (RCTs) from 1944 to 2020, located through hand and electronic searching; CENTRAL; MEDLINE; Embase; four other databases; and abstracts in selected publications.
SELECTION CRITERIA
We included RCTs comparing antibiotics with placebo or other antibiotics for the treatment of PID in women of reproductive age, either as inpatient or outpatient treatment. We limited our review to a comparison of drugs in current use that are recommended by the 2015 US Centers for Disease Control and Prevention guidelines for treatment of PID.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Two authors independently extracted data, assessed risk of bias and conducted GRADE assessments of the quality of evidence.
MAIN RESULTS
We included 39 RCTs (6894 women) in this review, adding two new RCTs at this update. The quality of the evidence ranged from very low to high, the main limitations being serious risk of bias (due to poor reporting of study methods and lack of blinding), serious inconsistency, and serious imprecision. None of the studies reported quinolones and cephalosporins, or the outcomes laparoscopic evidence of resolution of PID based on physician opinion or fertility outcomes. Length of stay results were insufficiently reported for analysis. Regimens containing azithromycin versus regimens containing doxycycline We are uncertain whether there was a clinically relevant difference between azithromycin and doxycycline in rates of cure for mild-moderate PID (RR 1.18, 95% CI 0.89 to 1.55; 2 RCTs, 243 women; I = 72%; very low-quality evidence). The analyses may result in little or no difference between azithromycin and doxycycline in rates of severe PID (RR 1.00, 95% CI 0.96 to 1.05; 1 RCT, 309 women; low-quality evidence), or adverse effects leading to discontinuation of treatment (RR 0.71, 95% CI 0.38 to 1.34; 3 RCTs, 552 women; I = 0%; low-quality evidence). In a sensitivity analysis limited to a single study at low risk of bias, azithromycin probably improves the rates of cure in mild-moderate PID (RR 1.35, 95% CI 1.10 to 1.67; 133 women; moderate-quality evidence), compared to doxycycline. Regimens containing quinolone versus regimens containing cephalosporin The analysis shows there may be little or no clinically relevant difference between quinolones and cephalosporins in rates of cure for mild-moderate PID (RR 1.05, 95% CI 0.98 to 1.14; 4 RCTs, 772 women; I = 15%; low-quality evidence), or severe PID (RR 1.06, 95% CI 0.91 to 1.23; 2 RCTs, 313 women; I = 7%; low-quality evidence). We are uncertain whether there was a difference between quinolones and cephalosporins in adverse effects leading to discontinuation of treatment (RR 2.24, 95% CI 0.52 to 9.72; 6 RCTs, 1085 women; I = 0%; very low-quality evidence). Regimens with nitroimidazole versus regimens without nitroimidazole There was probably little or no difference between regimens with or without nitroimidazoles (metronidazole) in rates of cure for mild-moderate PID (RR 1.02, 95% CI 0.95 to 1.09; 6 RCTs, 2660 women; I = 50%; moderate-quality evidence), or severe PID (RR 0.96, 95% CI 0.92 to 1.01; 11 RCTs, 1383 women; I = 0%; moderate-quality evidence). The evidence suggests that there was little to no difference in in adverse effects leading to discontinuation of treatment (RR 1.05, 95% CI 0.69 to 1.61; 17 studies, 4021 women; I = 0%; low-quality evidence). . In a sensitivity analysis limited to studies at low risk of bias, there was little or no difference for rates of cure in mild-moderate PID (RR 1.05, 95% CI 1.00 to 1.12; 3 RCTs, 1434 women; I = 0%; high-quality evidence). Regimens containing clindamycin plus aminoglycoside versus quinolone We are uncertain whether quinolone have little to no effect in rates of cure for mild-moderate PID compared to clindamycin plus aminoglycoside (RR 0.88, 95% CI 0.69 to 1.13; 1 RCT, 25 women; very low-quality evidence). The analysis may result in little or no difference between quinolone vs. clindamycin plus aminoglycoside in severe PID (RR 1.02, 95% CI 0.87 to 1.19; 2 studies, 151 women; I = 0%; low-quality evidence). We are uncertain whether quinolone reduces adverse effects leading to discontinuation of treatment (RR 0.21, 95% CI 0.02 to 1.72; 3 RCTs, 163 women; I = 0%; very low-quality evidence). Regimens containing clindamycin plus aminoglycoside versus regimens containing cephalosporin We are uncertain whether clindamycin plus aminoglycoside improves the rates of cure for mild-moderate PID compared to cephalosporin (RR 1.02, 95% CI 0.95 to 1.09; 2 RCTs, 150 women; I = 0%; low-quality evidence). There was probably little or no difference in rates of cure in severe PID with clindamycin plus aminoglycoside compared to cephalosporin (RR 1.00, 95% CI 0.95 to 1.06; 10 RCTs, 959 women; I= 21%; moderate-quality evidence). We are uncertain whether clindamycin plus aminoglycoside reduces adverse effects leading to discontinuation of treatment compared to cephalosporin (RR 0.78, 95% CI 0.18 to 3.42; 10 RCTs, 1172 women; I = 0%; very low-quality evidence).
AUTHORS' CONCLUSIONS
We are uncertain whether one treatment was safer or more effective than any other for the cure of mild-moderate or severe PID Based on a single study at a low risk of bias, a macrolide (azithromycin) probably improves the rates of cure of mild-moderate PID, compared to tetracycline (doxycycline).
Topics: Adolescent; Adult; Aminoglycosides; Anti-Bacterial Agents; Azithromycin; Cephalosporins; Clindamycin; Doxycycline; Drug Therapy, Combination; Female; Humans; Nitroimidazoles; Pelvic Inflammatory Disease; Publication Bias; Quinolones; Randomized Controlled Trials as Topic
PubMed: 32820536
DOI: 10.1002/14651858.CD010285.pub3 -
The Lancet. Microbe Oct 2022Surgical site infection (SSI) is the most common postoperative complication and substantially increases health-care costs. Published meta-analyses and international... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Surgical site infection (SSI) is the most common postoperative complication and substantially increases health-care costs. Published meta-analyses and international guidelines differ with regard to which preoperative skin antiseptic solution and concentration has the highest efficacy. We aimed to compare the efficacy of different skin preparation solutions and concentrations for the prevention of SSIs, and to provide an overview of current guidelines.
METHODS
This systematic review and network meta-analysis compared different preoperative skin antiseptics in the prevention of SSIs in adult patients undergoing surgery of any wound classification. We searched for randomised controlled trials (RCTs) in MEDLINE, Embase, and Cochrane CENTRAL, published up to Nov 23, 2021, that directly compared two or more antiseptic agents (ie, chlorhexidine, iodine, or olanexidine) or concentrations in aqueous and alcohol-based solutions. We excluded paediatric, animal, and non-randomised studies, and studies not providing standard preoperative intravenous antibiotic prophylaxis. Studies with no SSIs in both groups were excluded from the quantitative analysis. Two reviewers screened and reviewed eligible full texts and extracted data. The primary outcome was the occurrence of SSI (ie, superficial, deep, and organ space). We conducted a frequentist random effects network meta-analysis to estimate the network effects of the skin preparation solutions on the prevention of SSIs. A risk-of-bias and Grading of Recommendations, Assessment, Development, and Evaluation assessment were done to determine the certainty of the evidence. This study is registered with PROSPERO, CRD42021293554.
FINDINGS
Overall, 2326 articles were identified, 33 studies were eligible for the systematic review, and 27 studies with 17 735 patients reporting 2144 SSIs (overall incidence of 12·1%) were included in the quantitative analysis. Only 2·0-2·5% chlorhexidine in alcohol (relative risk 0·75, 95% CI 0·61-0·92) and 1·5% olanexidine (0·49, 0·26-0·92) significantly reduced the rate of SSIs compared with aqueous iodine. For clean surgery, we found no difference in efficacy between different concentrations of chlorhexidine in alcohol. Seven RCTs were at high risk of bias, 24 had some concerns, and two had low risk of bias. Heterogeneity across the studies was moderate (I=27·5%), and netsplitting did not show inconsistencies between direct and indirect comparisons. Five of ten studies that mentioned adverse events related to the skin preparation solutions reported no adverse events, and five reported a total of 56 mild events (mainly erythema, pruritus, dermatitis, skin irritation, or mild allergic symptoms); none reported a substantial difference in adverse events between groups.
INTERPRETATION
For adult patients undergoing a surgical procedure of any wound classification, skin preparation using either 2·0-2·5% chlorhexidine in alcohol or 1·5% olanexidine is most effective in the prevention of SSIs. For clean surgery, no specific concentration of chlorhexidine in alcohol can be recommended. The efficacy of olanexidine was established by a single randomised trial and further investigation is needed.
FUNDING
Dutch Association for Quality Funds Medical Specialists.
Topics: Anti-Infective Agents, Local; Biguanides; Chlorhexidine; Ethanol; GRADE Approach; Humans; Incidence; Iodine; Network Meta-Analysis; Povidone-Iodine; Surgical Wound Infection
PubMed: 35985350
DOI: 10.1016/S2666-5247(22)00187-2 -
The Cochrane Database of Systematic... Jun 2020The risk of maternal mortality and morbidity is higher after caesarean section than for vaginal birth. With increasing rates of caesarean section, it is important to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The risk of maternal mortality and morbidity is higher after caesarean section than for vaginal birth. With increasing rates of caesarean section, it is important to minimise risks to the mother as much as possible. This review focused on different skin preparations to prevent infection. This is an update of a review last published in 2018.
OBJECTIVES
To compare the effects of different antiseptic agents, different methods of application, or different forms of antiseptic used for preoperative skin preparation for preventing postcaesarean infection.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (9 July 2019), and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised and quasi-randomised trials, evaluating any type of preoperative skin preparation (agents, methods or forms). We included studies presented only as abstracts, if there was enough information to assess risk of bias. Comparisons of interest in this review were between: different antiseptic agents (e.g. alcohol, povidone iodine), different methods of antiseptic application (e.g. scrub, paint, drape), different forms of antiseptic (e.g. powder, liquid), and also between different packages of skin preparation including a mix of agents and methods, such as a plastic incisional drape, which may or may not be impregnated with antiseptic agents. We mainly focused on the comparison between different agents, with and without the use of drapes. Only studies involving the preparation of the incision area were included. This review did not cover studies of preoperative handwashing by the surgical team or preoperative bathing.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed all potential studies for inclusion, assessed risk of bias, extracted the data and checked data for accuracy. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 13 individually-randomised controlled trials (RCTs), with a total of 6938 women who were undergoing caesarean section. Twelve trials (6916 women) contributed data to this review. The trial dates ranged from 1983 to 2016. Six trials were conducted in the USA, and the remainder in India, Egypt, Nigeria, South Africa, France, Denmark, and Indonesia. The included studies were broadly at low risk of bias for most domains, although high risk of detection bias raised some specific concerns in a number of studies. Length of stay was only reported in one comparison. Antiseptic agents Parachlorometaxylenol with iodine versus iodine alone We are uncertain whether parachlorometaxylenol with iodine made any difference to the incidence of surgical site infection (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.04 to 2.99; 1 trial, 50 women), or endometritis (RR 0.88, 95% CI 0.56 to 1.38; 1 trial, 50 women) when compared with iodine alone, because the certainty of the evidence was very low. Adverse events (maternal or neonatal) were not reported. Chlorhexidine gluconate versus povidone iodine Moderate-certainty evidence suggested that chlorhexidine gluconate, when compared with povidone iodine, probably slightly reduces the incidence of surgical site infection (RR 0.72, 95% CI 0.58 to 0.91; 8 trials, 4323 women). This effect was still present in a sensitivity analysis after removing four trials at high risk of bias for outcome assessment (RR 0.87, 95% CI 0.62 to 1.23; 4 trials, 2037 women). Low-certainty evidence indicated that chlorhexidine gluconate, when compared with povidone iodine, may make little or no difference to the incidence of endometritis (RR 0.95, 95% CI 0.49 to 1.86; 3 trials, 2484 women). It is uncertain whether chlorhexidine gluconate reduces maternal skin irritation or allergic skin reaction (RR 0.64, 95% CI 0.28 to 1.46; 3 trials, 1926 women; very low certainty evidence). One small study (60 women) reported reduced bacterial growth at 18 hours after caesarean section for women who had chlorhexidine gluconate preparation compared with women who had povidone iodine preparation (RR 0.23, 95% CI 0.07 to 0.70). Methods Drape versus no drape This comparison investigated the use of drape versus no drape, following preparation of the skin with antiseptics. Low-certainty evidence suggested that using a drape before surgery compared with no drape, may make little or no difference to the incidence of surgical site infection (RR 1.29, 95% confidence interval (CI) 0.97 to 1.71; 3 trials, 1373 women), and probably makes little or no difference to the length of stay in the hospital (mean difference (MD) 0.10 days, 95% CI -0.27 to 0.46; 1 trial, 603 women; moderate-certainty evidence). One trial compared an alcohol scrub and iodophor drape with a five-minute iodophor scrub only, and reported no surgical site infection in either group (79 women, very-low certainty evidence). We were uncertain whether the combination of a one-minute alcohol scrub and a drape reduced the incidence of metritis when compared with a five-minute scrub, because the certainty of the evidence was very low (RR 1.62, 95% CI 0.29 to 9.16; 1 trial, 79 women). The studies did not report on adverse events (maternal or neonatal).
AUTHORS' CONCLUSIONS
Moderate-certainty evidence suggests that preparing the skin with chlorhexidine gluconate before caesarean section is probably slightly more effective at reducing the incidence of surgical site infection in comparison to povidone iodine. For other outcomes examined there was insufficient evidence available from the included RCTs. Most of the evidence in this review was deemed to be very low or low certainty. This means that for most findings, our confidence in any evidence of an intervention effect is limited, and indicates the need for more high-quality research. Therefore, it is not yet clear what sort of skin preparation may be most effective for preventing postcaesarean surgical site infection, or for reducing other undesirable outcomes for mother and baby. Well-designed RCTs, with larger sample sizes are needed. High-priority questions include comparing types of antiseptic (especially iodine versus chlorhexidine), and application methods (scrubbing, swabbing, or draping). We found two studies that are ongoing; we will incorporate the results of these studies in future updates of this review.
Topics: Adult; Anti-Infective Agents, Local; Bandages; Cesarean Section; Chlorhexidine; Endometritis; Ethanol; Female; Humans; Iodine; Iodophors; Length of Stay; Povidone-Iodine; Pregnancy; Preoperative Care; Randomized Controlled Trials as Topic; Surgical Drapes; Surgical Wound Infection; Xylenes
PubMed: 32580252
DOI: 10.1002/14651858.CD007462.pub5