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The Cochrane Database of Systematic... Jun 2017The pattern of infections among neutropenic patients with cancer has shifted in the last decades to a predominance of gram-positive infections. Some of these... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The pattern of infections among neutropenic patients with cancer has shifted in the last decades to a predominance of gram-positive infections. Some of these gram-positive bacteria are increasingly resistant to beta-lactams and necessitate specific antibiotic treatment.
OBJECTIVES
To assess the effectiveness of empirical anti-gram-positive (antiGP) antibiotic treatment for febrile neutropenic patients with cancer in terms of mortality and treatment failure. To assess the rate of resistance development, further infections and adverse events associated with additional antiGP treatment.
SEARCH METHODS
For the review update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (May 2012 to 2017), Embase (May 2012 to 2017), LILACS (2012 to 2017), conference proceedings, ClinicalTrials.gov trial registry, and the references of the included studies. We contacted the first authors of all included and potentially relevant trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing one antibiotic regimen versus the same regimen with the addition of an antiGP antibiotic for the treatment of febrile neutropenic patients with cancer.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility and risk of bias, and extracted all data. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated. A random-effects model was used for all comparisons showing substantial heterogeneity (I > 50%). Outcomes were extracted by intention-to-treat and the analysis was patient-based whenever possible.
MAIN RESULTS
Fourteen trials and 2782 patients or episodes were included. Empirical antiGP antibiotics were tested at the onset of treatment in 12 studies, and for persistent fever in two studies. The antiGP treatment was a glycopeptide in nine trials. Eight studies were assessed in the overall mortality comparison and no significant difference was seen between the comparator arms, RR of 0.90 (95% CI 0.64 to 1.25; 8 studies, 1242 patients; moderate-quality data). Eleven trials assessed failure, including modifications as failures, while seven assessed overall failure disregarding treatment modifications. Failure with modifications was reduced, RR of 0.72 (95% CI 0.65 to 0.79; 11 studies, 2169 patients; very low-quality data), while overall failure was the same, RR of 1.00 (95% CI 0.79 to 1.27; 7 studies, 943 patients; low-quality data). Sensitivity analysis for allocation concealment and incomplete outcome data did not change the results. Failure among patients with gram-positive infections was reduced with antiGP treatment, RR of 0.56 (95% CI 0.38 to 0.84, 5 studies, 175 patients), although, mortality among these patients was not changed.Data regarding other patient subgroups likely to benefit from antiGP treatment were not available. Glycopeptides did not increase fungal superinfection rates and were associated with a reduction in documented gram-positive superinfections. Resistant colonisation was not documented in the studies.
AUTHORS' CONCLUSIONS
Based on very low- or low-quality evidence using the GRADE approach and overall low risk of bias, the current evidence shows that the empirical routine addition of antiGP treatment, namely glycopeptides, does not improve the outcomes of febrile neutropenic patients with cancer.
Topics: Anti-Bacterial Agents; Febrile Neutropenia; Glycopeptides; Gram-Positive Bacterial Infections; Humans; Neoplasms; Randomized Controlled Trials as Topic; Treatment Failure
PubMed: 28577308
DOI: 10.1002/14651858.CD003914.pub4 -
The Cochrane Database of Systematic... Jun 2013Continued controversy surrounds the optimal empirical treatment for febrile neutropenia. New broad-spectrum beta-lactams have been introduced as single treatment, and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Continued controversy surrounds the optimal empirical treatment for febrile neutropenia. New broad-spectrum beta-lactams have been introduced as single treatment, and classically, a combination of a beta-lactam with an aminoglycoside has been used.
OBJECTIVES
To compare beta-lactam monotherapy versus beta-lactam-aminoglycoside combination therapy for cancer patients with fever and neutropenia.
SEARCH METHODS
The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2012), LILACS (August 2012), MEDLINE and EMBASE (August 2012) and the Database of Abstracts of Reviews of Effects (DARE) (Issue 3, 2012). We scanned references of all included studies and pertinent reviews and contacted the first author of each included trial, as well as the pharmaceutical companies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing any beta-lactam antibiotic monotherapy with any combination of a beta-lactam and an aminoglycoside antibiotic, for the initial empirical treatment of febrile neutropenic cancer patients. All cause mortality was the primary outcome assessed.
DATA COLLECTION AND ANALYSIS
Data concerning all cause mortality, infection related mortality, treatment failure (including treatment modifications), super-infections, adverse effects and study quality measures were extracted independently by two review authors. Risk ratios (RRs) with their 95% confidence intervals (CIs) were estimated. Outcomes were extracted by intention-to-treat (ITT) analysis whenever possible. Individual domains of risk of bias were examined through sensitivity analyses. Published data were complemented by correspondence with authors.
MAIN RESULTS
Seventy-one trials published between 1983 and 2012 were included. All cause mortality was lower with monotherapy (RR 0.87, 95% CI 0.75 to 1.02, without statistical significance). Results were similar for trials comparing the same beta-lactam in both trial arms (11 trials, 1718 episodes; RR 0.74, 95% CI 0.53 to 1.06) and for trials comparing different beta-lactams-usually a broad-spectrum beta-lactam compared with a narrower-spectrum beta-lactam combined with an aminoglycoside (33 trials, 5468 episodes; RR 0.91, 95% CI 0.77 to 1.09). Infection related mortality was significantly lower with monotherapy (RR 0.80, 95% CI 0.64 to 0.99). Treatment failure was significantly more frequent with monotherapy in trials comparing the same beta-lactam (16 trials, 2833 episodes; RR 1.11, 95% CI 1.02 to 1.20), and was significantly more frequent with combination therapy in trials comparing different beta-lactams (55 trials, 7736 episodes; RR 0.92, 95% CI 0.88 to 0.97). Bacterial super-infections occurred with equal frequency, and fungal super-infections were more common with combination therapy. Adverse events were more frequent with combination therapy (numbers needed to harm 4; 95% CI 4 to 5). Specifically, the difference with regard to nephrotoxicity was highly significant. Adequate trial methods were associated with a larger effect estimate for mortality and smaller effect estimates for failure. Nearly all trials were open-label. No correlation was noted between mortality and failure rates and these trials.
AUTHORS' CONCLUSIONS
Beta-lactam monotherapy is advantageous compared with beta-lactam-aminoglycoside combination therapy with regard to survival, adverse events and fungal super-infections. Treatment failure should not be regarded as the primary outcome in open-label trials, as it reflects mainly treatment modifications.
Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Cause of Death; Child; Combined Modality Therapy; Humans; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic; beta-Lactams
PubMed: 23813455
DOI: 10.1002/14651858.CD003038.pub2 -
BMJ (Clinical Research Ed.) May 2003To compare the effectiveness of beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in the treatment of patients with fever and neutropenia. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the effectiveness of beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in the treatment of patients with fever and neutropenia.
DATA SOURCES
Medline, Embase, Lilacs, the Cochrane Library, and conference proceedings to 2002. References of included studies and contact with authors. No restrictions on language, year of publication, or publication status.
STUDY SELECTION
All randomised trials of beta lactam monotherapy compared with beta lactam-minoglycoside combination therapy as empirical treatment for patients with fever and neutropenia.
DATA SELECTION
Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. An intention to treat approach was used. Relative risks were pooled with the random effect model.
MAIN OUTCOME MEASURE
All cause fatality.
RESULTS
Forty seven trials with 7807 patients met inclusion criteria. Nine trials compared the same beta lactam. There was no significant difference in all cause fatality (relative risk 0.85, 95% confidence interval 0.72 to 1.02). For success of treatment there was a significant advantage with monotherapy (0.92, 0.85 to 0.99), though there was considerable heterogeneity among trials. There was no significant difference between monotherapy and combination treatment in trials that compared the same beta lactam, whereas there was major advantage with monotherapy in trials that compared different beta lactams (0.87, 0.80 to 0.93). Rates of superinfection were similar. Adverse events, including those associated with severe morbidity, were significantly more common in the combination treatment group. Detected flaws in methods did not affect results.
CONCLUSIONS
For patients with fever and neutropenia there is no clinical advantage in treatment with beta lactam-aminoglycoside combination therapy. Broad spectrum beta lactams as monotherapy should be regarded as the standard of care for such patients.
Topics: Aminoglycosides; Anti-Bacterial Agents; Cause of Death; Drug Therapy, Combination; Fever; Humans; Neutropenia; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Superinfection; Treatment Failure; beta-Lactams
PubMed: 12763980
DOI: 10.1136/bmj.326.7399.1111 -
Supportive Care in Cancer : Official... Apr 2002The effectiveness of granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) in the treatment of febrile neutropenic cancer patients remains... (Meta-Analysis)
Meta-Analysis Review
Therapeutic use of granulocyte and granulocyte-macrophage colony-stimulating factors in febrile neutropenic cancer patients. A systematic review of the literature with meta-analysis.
The effectiveness of granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) in the treatment of febrile neutropenic cancer patients remains controversial. To assess their role in this condition, we conducted a systematic review of randomised trials published as full papers. A methodological evaluation using a specifically designed quality scale was performed before meta-analysis. Eleven trials were eligible, 8 of which were meta-analysable. The median quality score for the 11 pooled trials was 58.3% (range: 33.3%-68.8%). No significant quality difference was observed between positive (colony-stimulating factor more effective) and negative trials ( P=0.36). No quality difference was observed between the 8 meta-analysable studies and the 3 others, with respective median scores of 59.3% and 50%. No advantage was detected for the use of CSF in terms of mortality from febrile neutropenia, with a relative risk of 0.71 (95% CI 0.44-1.15). The relative risk was 0.66 (95% CI 0.39-1.13) in the G-CSF subgroup and 0.97 (95% CI 0.34-2.79) in the GM-CSF subgroup. Aggregation of the results on infection-related mortality, length of stay in hospital, fever and of neutropenia duration, antibiotic therapy adaptation and duration, superinfection rate and toxicity was not possible owing to the lack of adequate data in the publications. On the basis of this review, we cannot recommend the routine use of G-CSF or GM-CSF in established febrile neutropenia.
Topics: Anti-Bacterial Agents; Fever; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Length of Stay; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 11904782
DOI: 10.1007/s00520-001-0312-5 -
Diseases (Basel, Switzerland) Aug 2022Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent for the Coronavirus Disease 2019 (COVID-19) pandemic, has sparked a medical emergency... (Review)
Review
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent for the Coronavirus Disease 2019 (COVID-19) pandemic, has sparked a medical emergency worldwide. With the rise in COVID-19 infections and an eventual increase in hospitalized critically ill patients, a trend of bacterial, fungal, and viral superinfection has been noted. One important agent of co-infection identified is . Due to its multidrug-resistant nature and easy transmissibility, is difficult to manage in COVID-positive patients. Patients with comorbidities, immunosuppressive states, intubated and on ventilators are more likely to contract the fungal infection. Therefore, it is essential to the first screen, diagnose, and isolate patients with infection and manage and treat them while preventing the spread of the disease. Failure to recognize and prevent its spread may lead to an eventual epidemic or even a pandemic during the current COVID-pandemic, which the exhausted healthcare system can most definitely not handle. This systematic review investigates the prevalence of , its pathophysiology, diagnosis, prevention, and treatment during the COVID-19 pandemic.
PubMed: 36135214
DOI: 10.3390/diseases10030058 -
Gut Mar 2019Hepatitis D virus (HDV) is a defective virus that completes its life cycle only with hepatitis B virus (HBV). The HBV with HDV super-infection has been considered as one... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hepatitis D virus (HDV) is a defective virus that completes its life cycle only with hepatitis B virus (HBV). The HBV with HDV super-infection has been considered as one of the most severe forms of the chronic viral hepatitis. However, there is a scarcity of data on the global burden of HDV infection.
DESIGN
We searched PubMed, Embase, Cochrane Library and China Knowledge Resource Integrated databases from 1 January 1977 to 31 December 2016. We included studies with a minimum sample size of 50 patients. Our study analysed data from a total of 40 million individuals to estimate the prevalence of HDV by using Der-Simonian Laird random-effects model. The data were further categorised according to risk factors.
RESULTS
From a total of 2717 initially identified studies, only 182 articles from 61 countries and regions met the final inclusion criteria. The overall prevalence of HDV was 0.98% (95% CI 0.61 to 1.42). In HBsAg-positive population, HDV pooled prevalence was 14.57% (95% CI 12.93 to 16.27): Seroprevalence was 10.58% (95% CI 9.14 to 12.11) in mixed population without risk factors of intravenous drug use (IVDU) and high-risk sexual behaviour (HRSB). It was 37.57% (95% CI 29.30 to 46.20) in the IVDU population and 17.01% (95% CI 10.69 to 24.34) in HRSB population.
CONCLUSION
We found that approximately 10.58% HBsAg carriers (without IVDU and HRSB) were coinfected with HDV, which is twofold of what has been estimated before. We also noted a substantially higher HDV prevalence in the IVDU and HRSB population. Our study highlights the need for increased focus on the routine HDV screening and rigorous implementation of HBV vaccine programme.
Topics: Coinfection; Global Health; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Hepatitis D; Humans; Prevalence; Risk Factors; Risk-Taking; Sexual Behavior; Substance Abuse, Intravenous
PubMed: 30228220
DOI: 10.1136/gutjnl-2018-316601 -
Immunity, Inflammation and Disease Jan 2023Infections with fungi, such as Aspergillus species, have been found as common complications of viral pneumonia. This study aims to determine the risk factors of fungal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Infections with fungi, such as Aspergillus species, have been found as common complications of viral pneumonia. This study aims to determine the risk factors of fungal superinfections in viral pneumonia patients using meta-analysis.
OBJECTIVE
This study aims to determine the risk factors of fungal infection s in viral pneumonia patients using meta-analysis.
METHODS
We reviewed primary literature about fungal infection in viral pneumonia patients published between January 1, 2010 and September 30, 2020, in the Chinese Biomedical Literature, Chinese National Knowledge Infrastructure, Wanfang (China), Cochrane Central Library, Embase, PubMed, and Web of Science databases. These studies were subjected to an array of statistical analyses, including risk of bias and sensitivity analyses.
RESULTS
In this study, we found a statistically significant difference in the incidence of fungal infections in viral pneumonia patients that received corticosteroid treatment as compared to those without corticosteroid treatment (p < .00001). Additionally, regarding the severity of fungal infections, we observed significant higher incidence of invasive pulmonary aspergillosis (IPA) in patients with high Acute Physiology and Chronic Health Evaluation (APACHE) II scores (p < .001), tumors (p = .005), or immunocompromised patients (p < .0001).
CONCLUSIONS
Our research shows that corticosteroid treatment was an important risk factor for the development of fungal infection in patients with viral pneumonia. High APACHE II scores, tumors, and immunocompromised condition are also important risk factors of developing IPA. The diagnosis of fungal infection in viral pneumonia patients can be facilitated by early serum galactomannan (GM) testing, bronchoalveolar lavage fluid Aspergillus antigen testing, culture, and biopsy.
Topics: Humans; Superinfection; Sensitivity and Specificity; Aspergillus; Invasive Pulmonary Aspergillosis; Risk Factors; Neoplasms
PubMed: 36705416
DOI: 10.1002/iid3.760 -
Journal of Neuro-oncology Apr 2014Rathke's cleft cysts (RCCs), also known as pars intermedia cysts, represent benign lesions formed from remnants of the embryologic Rathke's pouch. Commonly asymptomatic,... (Review)
Review
Rathke's cleft cysts (RCCs), also known as pars intermedia cysts, represent benign lesions formed from remnants of the embryologic Rathke's pouch. Commonly asymptomatic, they are identified in nearly 1 in 6 healthy volunteers undergoing brain imaging. When symptomatic, they can cause headaches, endocrine dysfunction, and, rarely, visual disturbances. A systematic review of the published English literature was performed focusing on large modern case series of RCCs to describe their natural history, clinicopathologic features, radiographic features, and surgical outcomes, including rates of recurrence. The natural history of asymptomatic RCCs is one of slow growth, suggesting that observation through serial magnetic resonance imaging is appropriate for smaller asymptomatic RCCs. Symptomatic RCCs can be treated by surgical resection with low morbidity, usually through an endonasal transsphenoidal corridor using either a microscope or an endoscope. Surgical treatment frequently provides symptomatic relief of headaches and visual disturbances, and sometimes even improves endocrine dysfunction. Rates of recurrence after surgical treatment range from 16 to 18 % in large series, and higher rates of recurrence are associated with suprasellar location, inflammation and reactive squamous metaplasia in the cyst wall, superinfection of the cyst, and use of a fat graft into the cyst cavity.
Topics: Central Nervous System Cysts; Humans
PubMed: 24146189
DOI: 10.1007/s11060-013-1272-6 -
Journal of Viral Hepatitis Feb 2023In individuals with underlying chronic liver disease (CLD), hepatitis E virus (HEV) infection is a potential trigger of acute-on-chronic liver failure. In this... (Meta-Analysis)
Meta-Analysis
In individuals with underlying chronic liver disease (CLD), hepatitis E virus (HEV) infection is a potential trigger of acute-on-chronic liver failure. In this systematic review, seven electronic databases were searched. Pooled incidence rates with 95% confidence intervals (95% CIs) were calculated by the Freeman-Tukey double arcsine transformation method. The association between death or liver failure and HEV superinfection in CLD patients was estimated by the odds ratios (OR) with a 95% CI. A total of 18 studies from 5 countries were eligible for systematic review. The prevalence of acute HEV infection in hospitalized CLD patients with clinical manifestations of hepatitis was 13.6%, which was significantly higher than that in CLD patients from the community (pooled prevalence 1.1%). The overall rates of liver failure and mortality in CLD patients with HEV superinfection were 35.8% (95% CI: 26.7%-45.6%) and 14.3% (95% CI: 10.6%-18.5%), respectively, with the rates in cirrhotic patients being approximately 2-fold and 4-fold higher than those in noncirrhotic patients, respectively. The risks of liver failure (OR = 5.5, 95% CI: 1.5-20.1) and mortality (OR = 5.0, 95% CI: 1.9-13.3) were significantly higher in CLD patients with HEV superinfection than in those without HEV superinfection. HEV testing in hospitalized CLD patients is necessary due to the high prevalence of HEV infection observed in hospitalized CLD patients. HEV superinfection could accelerate disease progression in patients with underlying CLD and increase mortality in these patients. HEV vaccination is appropriate for patients with pre-existing CLD.
Topics: Humans; Hepatitis E; Superinfection; Hepatitis E virus; Prognosis; Acute-On-Chronic Liver Failure
PubMed: 36177994
DOI: 10.1111/jvh.13754 -
The Cochrane Database of Systematic... Jan 2014Optimal antibiotic treatment for sepsis is imperative. Combining a beta lactam antibiotic with an aminoglycoside antibiotic may provide certain advantages over beta... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Optimal antibiotic treatment for sepsis is imperative. Combining a beta lactam antibiotic with an aminoglycoside antibiotic may provide certain advantages over beta lactam monotherapy.
OBJECTIVES
Our objectives were to compare beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in patients with sepsis and to estimate the rate of adverse effects with each treatment regimen, including the development of bacterial resistance to antibiotics.
SEARCH METHODS
In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11); MEDLINE (1966 to 4 November 2013); EMBASE (1980 to November 2013); LILACS (1982 to November 2013); and conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (1995 to 2013). We scanned citations of all identified studies and contacted all corresponding authors. In our previous review, we searched the databases to July 2004.
SELECTION CRITERIA
We included randomized and quasi-randomized trials comparing any beta lactam monotherapy versus any combination of a beta lactam with an aminoglycoside for sepsis.
DATA COLLECTION AND ANALYSIS
The primary outcome was all-cause mortality. Secondary outcomes included treatment failure, superinfections and adverse events. Two review authors independently collected data. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) using the fixed-effect model. We extracted outcomes by intention-to-treat analysis whenever possible.
MAIN RESULTS
We included 69 trials that randomly assigned 7863 participants. Twenty-two trials compared the same beta lactam in both study arms, while the remaining trials compared different beta lactams using a broader-spectrum beta lactam in the monotherapy arm. In trials comparing the same beta lactam, we observed no difference between study groups with regard to all-cause mortality (RR 0.97, 95% CI 0.73 to 1.30) and clinical failure (RR 1.11, 95% CI 0.95 to 1.29). In studies comparing different beta lactams, we observed a trend for benefit with monotherapy for all-cause mortality (RR 0.85, 95% CI 0.71 to 1.01) and a significant advantage for clinical failure (RR 0.75, 95% CI 0.67 to 0.84). No significant disparities emerged from subgroup and sensitivity analyses, including assessment of participants with Gram-negative infection. The subgroup of Pseudomonas aeruginosa infections was underpowered to examine effects. Results for mortality were classified as low quality of evidence mainly as the result of imprecision. Results for failure were classified as very low quality of evidence because of indirectness of the outcome and possible detection bias in non-blinded trials. We detected no differences in the rate of development of resistance. Nephrotoxicity was significantly less frequent with monotherapy (RR 0.30, 95% CI 0.23 to 0.39). We found no heterogeneity for all these comparisons.We included a small subset of studies addressing participants with Gram-positive infection, mainly endocarditis. We identified no difference between monotherapy and combination therapy in these studies.
AUTHORS' CONCLUSIONS
The addition of an aminoglycoside to beta lactams for sepsis should be discouraged. All-cause mortality rates are unchanged. Combination treatment carries a significant risk of nephrotoxicity.
Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cause of Death; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Randomized Controlled Trials as Topic; beta-Lactams
PubMed: 24395715
DOI: 10.1002/14651858.CD003344.pub3