Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials

OBJECTIVES: Early, empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia. Several beta-lactams are accepted for monotherapy. We asked whether patients' outcomes are influenced by the chosen beta-lactam. METHODS: Systematic review and meta-analysis of randomized controlled trials comparing anti-pseudomonal beta-lactams administered as empirical monotherapy for febrile neutropenia, with or without vancomycin. The search included The Cochrane Library, PubMed, Embase, Lilacs databases, bibliography, conference proceedings, trial registries and FDA new drug approvals. Two reviewers independently applied selection criteria, performed quality assessment and extracted the data. Trials assessing the same beta-lactam were pooled using the fixed effect model. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. The primary outcome assessed was all-cause mortality. RESULTS: Thirty-three trials fulfilled inclusion criteria. Cefepime was associated with higher all-cause mortality at 30 days than other beta-lactams (RR 1.44, 95% CI 1.06-1.94, 3123 participants). Carbapenems were associated with fewer treatment modifications, including addition of glycopeptides, than ceftazidime or other comparators. Adverse events were significantly more frequent with carbapenems, specifically pseudomembranous colitis (RR 1.94, 95% CI 1.24-3.04, 2025 participants). All-cause mortality was unaltered. Piperacillin/tazobactam was compared only with cefepime and carbapenems, in six trials. No significant differences were demonstrated with paucity of data for all-cause mortality. CONCLUSIONS: The use of cefepime for febrile neutropenia is associated with increased mortality and should be carefully considered pending further analysis. Empirical use of carbapenems entails fewer treatment modifications, but an increased rate of pseudomembranous colitis. Ceftazidime, piperacillin/tazobactam, imipenem/cilastatin and meropenem appear to be suitable agents for monotherapy.     

Empirical antibiotics against Gram-positive infections for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials

OBJECTIVES: To assess the value of empirical anti-Gram-positive antibiotics for the treatment of febrile neutropenia. METHODS: Systematic review and meta-analysis of randomized controlled trials comparing antibiotics with anti-Gram-positive spectrum to control or placebo, in addition to the same baseline antibiotic regimen in both arms. We searched MEDLINE, EMBASE, LILACS, the Cochrane Library, conference proceedings, and references. No restrictions on inclusion were imposed. Two reviewers independently applied selection criteria, carried out quality assessment, and extracted the data. Relative risks with 95% confidence intervals were pooled using the fixed effect model. The primary outcome assessed was all-cause mortality. RESULTS: Thirteen studies met inclusion criteria, including 2392 participants. Glycopeptides were assessed in nine trials. Empirical anti-Gram-positive antibiotics were assessed for the initial treatment in 11 studies, and for persistent fever in two. No significant difference in all-cause mortality was seen [RR 0.86 (0.58-1.26), seven studies, 852 participants]. Overall failure at end of therapy occurred equally [RR 1.00 (0.79-1.27), six studies, 943 participants]. Failure associated with treatment modifications was more frequent in the control arm when empirical initial glycopeptides were assessed [RR 0.70 (0.61-0.80), five studies, 1178 participants]. Bacterial superinfections, mainly Gram-positive, were detected less frequently in the intervention arm. Adverse events were significantly more common with the additional antibiotic, and nephrotoxicity was significantly more common with additional glycopeptides [RR 1.88 (1.10-3.22), six studies, 1282 participants]. No significant heterogeneity was present in these comparisons. CONCLUSIONS: The use of glycopeptides can be safely deferred until the documentation of a resistant Gram-positive infection.     

Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients: a systematic review and meta-analysis of randomized trials

CONTEXT: Neutropenia is one of the grave consequences of cancer chemotherapy, and the treatment of neutropenic febrile patients with intravenous (iv) antibiotics has been shown to reduce mortality. Oral therapy could be an alternative approach for selected patients. OBJECTIVES: To compare the efficacy of oral antibiotics versus iv antibiotic therapy in febrile neutropenic cancer patients. DATA SOURCES: The Cochrane Library, the Cochrane Cancer Network Register of trials, EMBASE, LILACS and MEDLINE, databases for ongoing trials and the conference proceedings of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). STUDY SELECTION: Randomized controlled trials comparing oral antibiotic/s and iv antibiotic/s for the treatment of neutropenic cancer patients with fever. DATA COLLECTION: Two reviewers independently assessed trial eligibility, methodological quality and extracted all data. Data concerning mortality, treatment failures and adverse events were drawn from included studies assuming an 'intention-to-treat' and 'per-protocol' basis for the outcome measures whenever possible. Relative risks (RR) with their 95% confidence intervals (CI) for dichotomous data were estimated. MAIN RESULTS: Fifteen trials (median mortality 0, range 0%-8.8%) were included in the analyses. The mortality rate was similar comparing oral and iv antibiotic treatment (RR 0.83, 95% CI 0.49-1.41, 2224 patients). Treatment failure rates were also similar (RR 0.94, 95% CI 0.84-1.05, 15 trials). No significant heterogeneity was shown for the primary outcomes. This effect was stable in a wide range of patients. Quinolones alone or combined with other antibiotics were used with comparable results. Adverse reactions, mostly gastrointestinal, were more common with oral antibiotics. CONCLUSIONS: Oral antibiotics may be safely offered to neutropenic patients with fever who are at low risk for mortality.     

The role of aminoglycosides in combination with a beta-lactam for the treatment of bacterial endocarditis: a meta-analysis of comparative trials

BACKGROUND: The addition of an aminoglycoside to a beta-lactam for the treatment of patients with infective endocarditis has been supported by data from laboratory and animal studies. Purpose: We sought to review the evidence from the available comparative clinical trials regarding the role of aminoglycosides in combination with a beta-lactam for the treatment of bacterial endocarditis caused by Gram-positive cocci. DATA SOURCES: The studies for our meta-analysis were retrieved from searches of the PubMed and Cochrane Central Register of Controlled Trials databases, as well as from the references cited in relevant articles. No limits were set regarding the language and date of publication of the studies. STUDY SELECTION: Included studies were prospective studies that provided comparative data regarding the effectiveness of the treatment and/or mortality in patients receiving monotherapy with a beta-lactam or beta-lactam/aminoglycoside combination therapy. DATA EXTRACTION: Two independent reviewers performed the literature search, study selection and extraction of data from relevant studies. DATA SYNTHESIS: No clinical trial comparing beta-lactam monotherapy with beta-lactam/aminoglycoside combination therapy for the treatment of enterococcal endocarditis was found. We performed a meta-analysis of five available comparative trials [four randomized controlled trials (RCTs) and one comparative prospective trial], which included 261 patients with bacterial endocarditis in native valves due to Staphylococcus aureus (four studies) or streptococci of the viridans group (one study). There was no statistically significant difference between beta-lactam monotherapy and beta-lactam/aminoglycoside combination therapy regarding mortality [odds ratio (OR) = 0.59, 95% confidence interval (95% CI) = 0.21-1.66], treatment success (OR = 1.25, 95% CI = 0.49-3.05), treatment success without surgery (OR = 1.66, 95% CI = 0.64-4.30) or relapse of endocarditis (OR = 0.79, 95% CI = 0.15-4.29). Nephrotoxicity was less common in the beta-lactam monotherapy arm than in the beta-lactam/aminoglycoside combination therapy arm (OR = 0.38, 95% CI = 0.16-0.88, P = 0.024). No difference between the two treatment arms was found in subanalyses of the four studies that included only patients with staphylococcal infections in terms of mortality (OR = 0.69, 95% CI = 0.26-1.86, fixed effects model), treatment success (OR = 1.27, 95% CI = 0.47-3.43, fixed effects model) or relapse (OR = 0.76, 95% CI = 0.12-4.92, fixed effects model). LIMITATIONS: The relatively small number of available comparative trials was the major limitation of this meta-analysis. CONCLUSIONS: The limited evidence from the available prospective comparative studies does not offer support for the addition of an aminoglycoside to beta-lactam treatment of patients with endocarditis caused by Gram-positive cocci. A large multicentre RCT is necessary to reach a definitive conclusion on this issue.     

Operative vs nonoperative treatment of displaced intra-articular calcaneal fracture: A meta-analysis of randomized controlled trials

AIM: To investigate clinical efficacy of displaced intra-articular calcaneal fracture (DIACF) following operation and nonoperation. METHODS: Literature search was performed of PubMed and Cochrane Library by two independent authors to identify randomized controlled trials (RCTs) comparing operative vs nonoperative treatment of DIACF from inception to December 31^st, 2013. RCT quality was evaluated by the modified Jadad scale. Dichotomous variables were pooled using risk ratios by review manager 5.3 software. Fixed-effects or random-effects models were adopted with P > 0.05 or P≤ 0.05 for heterogeneity tests, respectively. RESULTS: Eight RCTs comprising 767 cases met inclusion criteria. Results revealed that more surgically treated patients could resume pre-injury job (P = 0.006). No statistical differences were found between the two groups in residual pain (P = 0.33), shoe fitting problems (P = 0.07), limited walking distance (P = 0.56) or secondary late arthrodesis (P = 0.38). However, operative treatment was associated with a higher complication rate (P = 0.003). Subgroup analyses of specific complications revealed that except for a higher risk of superficial wound problems (P < 0.0001) in operative group, the two groups had similar complication rate in deep wound infection (P = 0.34), compartment syndrome (P = 0.46), thromboembolism (P = 0.32), reflex sympathetic dystrophy (P = 0.51) or traumatic arthritis secondary to DIACF (P = 0.43). CONCLUSION: Current evidence demonstrates that compared with operative treatment, conservative treatment of DIACF lead to similar clinical outcomes regarding residual pain, shoe fitting, walking distance and secondary subtalar arthrodesis but a significantly lower complication rate.     

Efficacy and safety of aminoglycoside monotherapy: systematic review and meta-analysis of randomized controlled trials

OBJECTIVES: This study sought to compare the efficacy and adverse effects of any aminoglycoside as a single antibiotic with other antibiotics for the treatment of patients with infection. METHODS: Systematic review of the literature and meta-analysis. We searched for randomized controlled trials comparing the efficacy of single aminoglycoside antibiotic treatment with one or more non-aminoglycoside antibiotic for patients with infection in the Cochrane Library, MEDLINE, EMBASE, LILACS, databases of ongoing trials and conference proceedings. Two reviewers assessed trial eligibility, quality and extracted data. Pooled relative risks (RR) with 95% confidence intervals (CI) were calculated for dichotomous data. RESULTS: The search yielded 37 trials of which 26 included patients with urinary tract infection. Aminoglycosides were equally effective as comparators in the analysis of the primary outcomes, all-cause mortality (RR 1.11, 95% CI 0.68, 1.81, 9 trials, 503 patients) and treatment failure (RR 1.10, 95% CI 0.96, 1.27, 32 trials, 1890 patients). Aminoglycosides were associated with a significantly higher rate of bacteriological failure at end of therapy (RR 1.44, 95% CI 1.21, 1.72, 27 trials, 1668 patients). Subgroup analyses according to quality of trial, type of antibiotics, source of infection and rate of clinical sepsis did not alter the outcomes. Less adverse effects in total but more nephrotoxic effects were observed in patients treated with aminoglycosides. CONCLUSIONS: The present data support the use of aminoglycosides for urinary tract infections. The paucity of trials including patients with sepsis or reporting on mortality precludes firm recommendations for patients with infections other than of the urinary tract.     

Ceftriaxone plus once daily aminoglycoside with filgrastim for treatment of febrile neutropenia: early hospital discharge vs. Standard In-patient care

BACKGROUND: In febrile neutropenic patients, ceftriaxone plus an aminoglycoside is effective for the treatment of infection, while filgrastim reduces the extent and duration of neutropenia. Because the once daily dosing regimen of this combination permits ambulatory treatment, there is a need to test criteria for early hospital discharge. METHODS: Hospitalized adult patients with febrile neutropenia (following chemotherapy) considered to be potentially treatable on a follow-up out-patient basis were entered into this open-label, multinational study. Patients received a once daily combination of ceftriaxone for > or =5 days, aminoglycoside for > or =2 days, and filgrastim until the absolute neutrophil count was > or =1.0x10(9)/l for 2 days. Those initially responding to therapy (reduction of fever by > or =1 degrees C within 72 h, and clinical improvement) were randomized into standard in-patient or follow-up out-patient treatment groups, the latter patients being discharged from hospital early, after meeting defined criteria. RESULTS: 105 patients were enrolled, of whom 21 initial non-responders were not randomized. Efficacy was evaluable in 80 patients. Success (resolution of fever and symptoms, maintained for 7 days after cessation of therapy, and eradication of infecting pathogens) was similar among in-patients (40/42, 95%) and out-patients (34/38, 89%). The duration of hospitalization was shorter for out-patients than in-patients (median of 4 vs. 6 days, respectively). No hospital readmissions were necessary in out-patients. All other efficacy parameters assessed were comparable in both groups, as was tolerability/safety. One potentially drug-related death was reported. CONCLUSIONS: Patients who satisfy prospectively defined criteria for early discharge can be treated safely on an out-patient basis with a regimen of once daily ceftriaxone plus an aminoglycoside with filgrastim. In addition to reducing healthcare costs, it may improve patients' quality of life. Copyright Copyright 1999 S. Karger AG, Basel.     

Fluoroquinolones vs beta-lactams for empirical treatment of immunocompetent patients with skin and soft tissue infections: a meta-analysis of randomized controlled trials

OBJECTIVE: To compare the effectiveness and safety of fluoroquinolones with beta-lactams in the treatment of patients with skin and soft tissue infections (SSTIs). METHODS: We searched the PubMed database, Cochrane Database of Controlled Trials, and references of relevant articles for study reports published between January 1980 and February 2006. RESULTS: Twenty randomized controlled trials that enrolled 4817 patients were included in the analysis. Fluoroquinolones as empirical treatment of patients with SSTIs were more effective than beta-lactams for the clinically evaluable patients (90.4% vs 88.2%; odds ratio [OR], 1.29; 95% confidence interval [CI], 1.00-1.66). This was also true in subset analyses of randomized controlled trials that studied ciprofloxacin (OR, 2.49; 95% CI, 1.45-4.26) and for patients with mild to moderate infections (OR, 1.83; 95% CI, 1.13-2.96). In contrast, no difference was found between the compared regimens for patients with moderate to severe infections (OR, 1.12; 95% CI, 0.80-1.55), for patients who did not receive third-generation cephalosporins as the comparator antibiotic (OR, 0.99; 95% CI, 0.73-1.34), or for the microbiologically evaluable patients (OR, 1.19; 95% CI, 0.89-1.59). Fluoroquinolones were also associated with more adverse effects (19.2% vs 15.2%; OR, 1.33; 95% CI, 1.13-1.57). CONCLUSION: The high proportion of successfully treated patients in the compared groups of antibiotics and the development of more adverse effects associated with fluoroquinolone use suggest that these antibiotics do not have substantial advantages compared with beta-lactams for empirical treatment of patients with SSTIs.     

Selenium supplementation for sepsis: a meta-analysis of randomized controlled trials

Background

Recently, several studies were conducted to investigate the effect of selenium supplementation in septic patients. However, no consistent conclusion was made. Thus, we aimed to systematically summarize the available randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on important clinical outcomes in septic patients.

Methods

A systematic literature search of Pubmed, Embase, and the Cochrane Central Register of Controlled Trials was conducted (up to August 25, 2012). RCTs were included if they reported the effect of selenium supplementation on the treatment of septic patients. A fixed-effect model was used, and in the case of significant heterogeneity, a random-effects model was employed.

Results

Five studies with a total of 530 patients were included. Pooled analysis showed that selenium supplementation did not reduce all-cause mortality (relative risk [RR] = 0.89, 95% confidence interval [CI]: 0.73-1.07, P = .21), hospital-acquired pneumonia (RR = 1.15, 95% CI: 0.73-1.82, P = .55), or length of intensive care unit stay (weighted mean differences = 2.32 days, 95% CI: − 0.05 to 4.69; P = .05). In addition, no significant difference was observed regarding adverse events between groups (RR = 0.97, 95% CI: 0.72-1.33, P = .87).

Conclusions

The present meta-analysis showed no benefit of selenium supplementation in patients with sepsis. Due to the limited number of RCTs included, more prospective multicenter clinical trials on selenium therapy in septic patients are warranted in the future.     

Monotherapy with a broad-spectrum beta-lactam is as effective as its combination with an aminoglycoside in treatment of severe generalized peritonitis: a multicenter randomized controlled trial. The Severe Generalized Peritonitis Study Group

In a randomized trial conducted in 35 centers, we compared the clinical efficacy and safety of piperacillin plus tazobactam (TAZ) alone (monotherapy [MT]) versus those of TAZ combined with amikacin (AMK) (combined therapy [CT]) for the treatment of severe generalized peritonitis (SGP). Primary analysis consisted of blind assessment by an independent committee of the failure rate 30 days after the end of treatment in the modified intent-to-treat (ITT) analysis (mITT) population. Of the 241 patients with suspected SGP randomized into the study, 227 were eligible for ITT analysis, including 204 (99 in the MT group and 105 in the CT group) with confirmed SGP (mITT population). A total of 159 patients were eligible for per-protocol (PP) analysis. The clinical failure rates were equivalent in the mITT and PP populations (MT versus CT): 56 versus 52%, (odds ratio [OR] 0.87, 90% confidence interval [CI] = 0. 6 to 1.27) for mITT and 49 versus 49% (OR = 1.03, 90% CI = 0.67 to 1. 59) for PP analysis. Mortality rates (ITT population, 19%; PP population, 21%) and overall adverse event rates (ITT population, 55%; PP population, 54%) were also similar. Six patients (three in MT group and three in the CT group) developed acute renal failure. In conclusion, the addition of AMK to TAZ does not seem to be necessary for the treatment of SGP, even after adjustment for the simplified acute physiology score (SAPS II) and type of SGP.     

阿托西班与利托君临床应用随机对照试验的Meta分析

目的评价阿托西班治疗早产的疗效和安全性。方法计算机全面检索MEDLINE(至2010年1月),EMbase(至2010年1月),Cochrane临床对照试验注册资料库(2010年第1期),收集阿托西班治疗早产的随机对照试验(RCT),对符合纳入标准的高质量临床研究应用RevMan 5.0软件进行Meta分析。结果共纳入高质量的RCT研究3篇。Meta分析结果显示,与利托君组相比,阿托西班组在新生儿窒息率、治疗有效率、分娩时的平均孕周和新生儿平均体质量方面无显著性差异(P>0.05),因副作用中断治疗率低(RR=0.03,95%CI 0.01~0.15,P<0.01),心动过速发生率低(RR=0.02,95%CI 0.01~0.08,P<0.01)。结论阿托西班治疗早产孕妇可以达到和利托君相当的效果,且其副作用发生率低。     

Platelet-rich plasma for the treatment of burn wounds: A meta-analysis of randomized controlled trials

BackgroundTo evaluate the efficacy and safety of platelet-rich plasma in the treatment of burn wounds through a meta-analysis of randomized controlled trials.MethodsWe conducted a comprehensive study from electronic medical journal databases. The primary outcome was healing rate, and the secondary outcomes were healing time, adverse events, pain score and scar score. The data was analyzed using Review Manager 5.3 and Stata 12. The odds ratio (OR) among different groups was calculated by using 95 % confidence interval (CI).ResultsWe included 8 randomized controlled trials with a total of 539 patients. The results showed that platelet-rich plasma could improve the healing rate of burn wound (OR 4.43, 95 % CI 2.13–9.22). The wound healing time of the platelet-rich plasma treatment group was significantly shorter than that of the conventional treatment group (OR –4.23, 95 % CI ?5.48 to ?2.98), both the superficial burn (OR –3.80, 95 % CI ?4.53 to ?3.07) and the deep burn group (OR –4.65, 95 % CI ?6.90 to ?2.40) had shorter healing time. Otherwise, the incidences of adverse events (OR 0.30, 95 % CI 0.11?0.78), pain score (OR –0.80, 95 % CI ?1.40 to ?0.21) and scar score (OR –0.38, 95 % CI ?0.69 to ?0.07) were all better in the platelet rich plasma treatment group.ConclusionTopical platelet-rich plasma treatment on burn wounds can improve wound healing and reduce the incidence of adverse events. Further research is needed to standardize the preparation and use of platelet-rich plasma and to evaluate the long-term clinical outcome of platelet-rich plasma in the treatment of burn wounds.     

Different dosage regimens of Eptinezumab for the treatment of migraine: a meta-analysis from randomized controlled trials

BackgroundMigraine is one of the most common neurological diseases around the world and calcitonin gene-related peptide (CGRP) plays an important role in its pathophysiology. Therefore, in the present study, we evaluated the efficacy of monoclonal antibodies blocking the CGRP ligand or receptor in episodic and chronic migraine.ObjectiveThe objective of our study is implementing a meta-analysis to systematically evaluate the efficacy and safety of eptinezumab for the treatment of migraine compared with placebo.MethodWe searched the Medline, Embase, Cochrane Library and Clinicaltrials.gov for randomized controlled trials (RCTs) which were performed to evaluate eptinezumab versus placebo for migraine up to September 2020. The data was assessed by Review Manager 5.3 software. The risk ratio (RR) and standard mean difference (SMD) were analyzed using dichotomous outcomes and continuous outcomes respectively with a random effect model.ResultWe collected 2739 patients from 4 RCTs: the primary endpoint of efficacy was the change from baseline to week 12 in mean monthly migraine days (MMDs). We found that eptinezumab (30 mg, 100 mg, 300 mg) led to a significant reduction in MMDs (P = 0.0001,P < 0.00001, P < 0.00001) during 12 weeks compared with placebo, especially with 300 mg. For the safety, we compared and concluded the treatment emergent adverse events (TEAEs) of the 4 RCTs. This indicated no evident statistical difference between eptinezumab and placebo.ConclusionsIn the present study, we found that eptinezumab is safe and has significant efficacy in the treatment of migraine, especially the dose of 300 mg.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01220-y.     

Vasopressin for cardiac arrest: meta-analysis of randomized controlled trials

Background

Prior meta-analyses-reported results of randomised controlled trials (RCTs) published between 1997 and 2004 failed to show any vasopressin-related benefit in cardiac arrest. Based on new RCT-data and a hypothesis of a potentially increased vasoconstricting efficacy of vasopressin, we sought to determine whether the cumulative, current evidence supports or refutes an overall and/or selective benefit for vasopressin regarding sustained restoration of spontaneous circulation (ROSC), long-term survival, and neurological outcome.

Methods

Two reviewers independently searched PubMed, EMBASE, and Cochrane Database for RCTs assigning adults with cardiac arrest to treatment with a vasopressin-containing regimen (vasopressin-group) vs adrenaline (epinephrine) alone (control-group) and reporting on long-term outcomes. Data from 4475 patients in 6 high-methodological quality RCTs were analyzed. Subgroup analyses were conducted according to initial cardiac rhythm and time from collapse to drug administration (T_DRUG) < 20 min.

Results

Vasopressin vs. control did not improve overall rates of sustained ROSC, long-term survival, or favourable neurological outcome. However, in asystole, vasopressin vs. control was associated with higher long-term survival {odds ratio (OR) = 1.80, 95% confidence interval (CI) = 1.04-3.12, P = 0.04}. In asystolic patients of RCTs with average T_DRUG < 20 min, vasopressin vs. control increased the rates of sustained ROSC (data available from 2 RCTs; OR = 1.70, 95% CI = 1.17-2.47, P = 0.005) and long-term survival (data available from 3 RCTs; OR = 2.84, 95% CI = 1.19-6.79, P = 0.02).

Conclusions

Vasopressin use in the resuscitation of cardiac arrest patients is not associated with any overall benefit or harm. However, vasopressin may improve the long-term survival of asystolic patients, especially when average T_DRUG is <20 min.