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The Cochrane Database of Systematic... Jan 2012Bacterial infections are a major cause of morbidity and mortality in patients who are neutropenic following chemotherapy for malignancy. Trials have shown the efficacy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bacterial infections are a major cause of morbidity and mortality in patients who are neutropenic following chemotherapy for malignancy. Trials have shown the efficacy of antibiotic prophylaxis in reducing the incidence of bacterial infections but not in reducing mortality rates. Our systematic review from 2006 also showed a reduction in mortality.
OBJECTIVES
This updated review aimed to evaluate whether there is still a benefit of reduction in mortality when compared to placebo or no intervention.
SEARCH METHODS
We searched the Cochrane Cancer Network Register of Trials (2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), abstracts of conference proceedings and the references of identified studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention, or another antibiotic, to prevent bacterial infections in afebrile neutropenic patients.
DATA COLLECTION AND ANALYSIS
Two authors independently appraised the quality of each trial and extracted data from the included trials. Analyses were performed using RevMan 5.1 software.
MAIN RESULTS
One-hundred and nine trials (involving 13,579 patients) that were conducted between the years 1973 to 2010 met the inclusion criteria. When compared with placebo or no intervention, antibiotic prophylaxis significantly reduced the risk of death from all causes (46 trials, 5635 participants; risk ratio (RR) 0.66, 95% CI 0.55 to 0.79) and the risk of infection-related death (43 trials, 5777 participants; RR 0.61, 95% CI 0.48 to 0.77). The estimated number needed to treat (NNT) to prevent one death was 34 (all-cause mortality) and 48 (infection-related mortality).Prophylaxis also significantly reduced the occurrence of fever (54 trials, 6658 participants; RR 0.80, 95% CI 0.74 to 0.87), clinically documented infection (48 trials, 5758 participants; RR 0.65, 95% CI 0.56 to 0.76), microbiologically documented infection (53 trials, 6383 participants; RR 0.51, 95% CI 0.42 to 0.62) and other indicators of infection.There were no significant differences between quinolone prophylaxis and TMP-SMZ prophylaxis with regard to death from all causes or infection, however, quinolone prophylaxis was associated with fewer side effects leading to discontinuation (seven trials, 850 participants; RR 0.37, 95% CI 0.16 to 0.87) and less resistance to the drugs thereafter (six trials, 366 participants; RR 0.45, 95% CI 0.27 to 0.74).
AUTHORS' CONCLUSIONS
Antibiotic prophylaxis in afebrile neutropenic patients significantly reduced all-cause mortality. In our review, the most significant reduction in mortality was observed in trials assessing prophylaxis with quinolones. The benefits of antibiotic prophylaxis outweighed the harm such as adverse effects and the development of resistance since all-cause mortality was reduced. As most trials in our review were of patients with haematologic cancer, we strongly recommend antibiotic prophylaxis for these patients, preferably with a quinolone. Prophylaxis may also be considered for patients with solid tumours or lymphoma.
Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Bacterial Infections; Cause of Death; Drug Resistance, Bacterial; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Neoplasms; Neutropenia; Quinolones; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 22258955
DOI: 10.1002/14651858.CD004386.pub3 -
The Cochrane Database of Systematic... Feb 2011To prevent the development of drug resistance, the World Health Organization (WHO) recommends treating malaria with combination therapy. Azithromycin, an antibiotic with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To prevent the development of drug resistance, the World Health Organization (WHO) recommends treating malaria with combination therapy. Azithromycin, an antibiotic with antimalarial properties, may be a useful additional option for antimalarial therapy.
OBJECTIVES
To compare the use of azithromycin alone or in combination with other antimalarial drugs with the use of alternative antimalarial drugs for treating uncomplicated malaria caused by Plasmodium falciparum or Plasmodium vivax.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group Specialized Register (August 2010); CENTRAL (The Cochrane Library Issue 3, 2010); MEDLINE (1966 to August 2010); EMBASE (1974 to August 2010); LILACS (August 2010); the metaRegister of Controlled Trials (mRCT, August 2010); conference proceedings; and reference lists. We also contacted researchers and a pharmaceutical company.
SELECTION CRITERIA
Randomized controlled trials comparing azithromycin, either alone or combined with another antimalarial drug, with another antimalarial drug used alone or combined with another antimalarial drug, or with azithromycin combined with another antimalarial drug if different combinations or doses of azithromycin were used. The primary outcome was treatment failure by day 28, defined as parasitological or clinical evidence of treatment failure between the start of treatment and day 28. Secondary outcomes included treatment failure by day 28 corrected for new infections confirmed by polymerase chain reaction (PCR), fever and parasite clearance time, and adverse events.
DATA COLLECTION AND ANALYSIS
Two people independently applied the inclusion criteria, extracted data and assessed methodological quality. We used risk ratio (RR) and 95% confidence intervals (CI).
MAIN RESULTS
Fifteen trials met the inclusion criteria (2284 participants, 69% males, 16% children). They were conducted in disparate malaria endemic areas, with the earlier studies conducted in Thailand (five) and India (two), and the more recent studies (eight) spread across three continents (South America, Africa, Asia). The 15 studies involved 41 treatment arms, 12 different drugs, and 28 different treatment regimens. Two studies examined P. vivax.Three-day azithromycin (AZ) monotherapy did not perform well for P. vivax or P. falciparum (Thailand: P. vivax failure rate 0.5 g daily, 56%, 95% CI 31 to 78. India: P. vivax failure rate 1 g daily,12%, 95% CI 7 to 21; P. falciparum failure rate 1 g daily, 64%, 95% CI 36 to 86.) A 1 g azithromycin and 0.6 g chloroquine combination daily for three days for uncomplicated P. falciparum infections was associated with increased treatment failure in India and Indonesia compared with the combination of sulphadoxine-pyrimethamine and chloroquine (pooled RR 2.66, 95% CI 1.25 to 5.67), and compared with the combination atovaquone-proguanil in a multicentre trial in Columbia and Surinam (RR 24.72, 95% CI 6.16 to 99.20). No increased risk of treatment failure was seen in two studies in Africa with mefloquine as the comparator drug (pooled RR 2.02, 95% CI 0.51 to 7.96, P = 0.3); the pooled RR for PCR-corrected data for the combination versus mefloquine was 1.01, 95% CI 0.18 to 5.84 (P = 1.0). An increased treatment failure risk was seen when comparing azithromycin in a dose of 1.2 to 1.5 mg in combination with artesunate (200 mg per day for three days) with artemether-lumefantrine (pooled RR 3.08, 95% CI 2.09 to 4.55; PCR-corrected pooled RR 3.63, 95% CI 2.02 to 6.52).Serious adverse events and treatment discontinuation were similar across treatment arms. More adverse events were reported when comparing the 1 g azithromycin/ 0.6 g chloroquine combination with mefloquine (pooled RR 1.20, 95% CI 1.06 to 1.36) or atovaquone-proguanil (RR 1.41, 95% CI 1.09 to1.83).
AUTHORS' CONCLUSIONS
Currently, there is no evidence for the superiority or equivalence of azithromycin monotherapy or combination therapy for the treatment of P. falciparum or P. vivax compared with other antimalarials or with the current first-line antimalarial combinations. The available evidence suggests that azithromycin is a weak antimalarial with some appealing safety characteristics. Unless the ongoing dose, formulation and product optimisation process results in a universally efficacious product, or a specific niche application is identified that is complementary to the current scala of more efficacious antimalarial combinations, azithromycin's future for the treatment of malaria does not look promising.
Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Artesunate; Atovaquone; Azithromycin; Chloroquine; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluorenes; Humans; Malaria, Falciparum; Malaria, Vivax; Male; Mefloquine; Proguanil; Pyrimethamine; Randomized Controlled Trials as Topic; Sulfadoxine; Treatment Failure
PubMed: 21328286
DOI: 10.1002/14651858.CD006688.pub2 -
The Cochrane Database of Systematic... Oct 2011Intermittent preventive treatment is recommended for pregnant women living in malaria endemic countries due to benefits for both mother and baby. However, the impact may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intermittent preventive treatment is recommended for pregnant women living in malaria endemic countries due to benefits for both mother and baby. However, the impact may not be the same in HIV-positive pregnant women, as HIV infection impairs a woman's immunity.
OBJECTIVES
To compare intermittent preventive treatment regimens for malaria in HIV-positive pregnant women living in malaria-endemic areas.
SEARCH STRATEGY
In June 2011, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE; EMBASE; LILACS, the metaRegister of Controlled Trials (mRCT), reference lists and conference abstracts. We also contacted researchers and organizations for information on relevant trials.
SELECTION CRITERIA
Randomized controlled trials comparing different intermittent preventive treatment regimens for preventing malaria in HIV-positive pregnant women in malaria-endemic areas.
DATA COLLECTION AND ANALYSIS
Two authors extracted data and assessed risk bias. Dichotomous variables were combined using risk ratios (RR) and mean differences (MD) for continuous outcomes, both with 95% confidence intervals (CI).
MAIN RESULTS
Two randomized trials with 722 HIV-positive pregnant women were included, comparing monthly regimens of sulfadoxine-pyrimethamine (SP) to the standard 2-dose regimen in the second and third trimesters. There were no statistically significant differences between monthly SP and 2-dose SP in rates of maternal anaemia, low birth weight, and neonatal mortality. In primigravidae and secondigravidiae, the monthly regimen was associated with less placental parasitaemia (RR 0.38, 95% CI 0.21 to 0.70, two trials) and less peripheral parasitaemia (RR 0.25, 95% CI 0.14 to 0.43, two trials), but no effect was demonstrated in multigravid women. Babies born to primigravidae and secundigravida women on monthly SP had a higher mean birth weight (weighted mean difference (WMD) 130 g; 95% CI 120 g to 150 g, two trials) than babies born to mothers on 2-dose SP. Multigravidae women treated with monthly SP had significant higher haemoglobin level than those treated with treated 2 dose SP (WMD 0.21 g/dL, 95% CI 0.15 g/dL to 0.27 g/dL, one trial). There were no trials that assessed other treatment regimens for intermittent preventive treatment in HIV-positive pregnant women.
AUTHORS' CONCLUSIONS
Three or more doses of SP is superior to the standard two doses in HIV-positive pregnant women. However, since SP cannot be administered concurrently with co-trimoxazole - a drug often recommended for infection prophylaxis in HIV-positive pregnant women, new drugs and research is needed to address needs of HIV-positive pregnant women.
Topics: Antimalarials; Drug Combinations; Female; HIV Seropositivity; Humans; Malaria; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Pyrimethamine; Randomized Controlled Trials as Topic; Sulfadoxine
PubMed: 21975756
DOI: 10.1002/14651858.CD006689.pub2 -
JAMA Feb 2013Intermittent preventive therapy with sulfadoxine-pyrimethamine to control malaria during pregnancy is used in 37 countries in sub-Saharan Africa, and 31 of those... (Meta-Analysis)
Meta-Analysis Review
Intermittent preventive therapy for malaria during pregnancy using 2 vs 3 or more doses of sulfadoxine-pyrimethamine and risk of low birth weight in Africa: systematic review and meta-analysis.
IMPORTANCE
Intermittent preventive therapy with sulfadoxine-pyrimethamine to control malaria during pregnancy is used in 37 countries in sub-Saharan Africa, and 31 of those countries use the standard 2-dose regimen. However, 2 doses may not provide protection during the last 4 to 10 weeks of pregnancy, a pivotal period for fetal weight gain.
OBJECTIVE
To perform a systematic review and meta-analysis of trials to determine whether regimens containing 3 or more doses of sulfadoxine-pyrimethamine for intermittent preventive therapy during pregnancy are associated with a higher birth weight or lower risk of low birth weight (LBW) (<2500 g) than standard 2-dose regimens.
DATA SOURCES AND STUDY SELECTION
ISI Web of Knowledge, EMBASE, SCOPUS, PubMed, LILACS, the Malaria in Pregnancy Library, Cochrane CENTRAL, and trial registries from their inception to December 2012, without language restriction. Eligible studies included randomized and quasi-randomized trials of intermittent preventive therapy during pregnancy with sulfadoxine-pyrimethamine monotherapy.
DATA EXTRACTION
Data were independently abstracted by 2 investigators. Relative risk (RR), mean differences, and 95% CIs were calculated with random-effects models.
RESULTS
Of 241 screened studies, 7 trials of 6281 pregnancies were included. The median birth weight in the 2-dose group was 2870 g (range, 2722-3239 g) and on average 56 g higher (95% CI, 29-83 g; I2 = 0%) in the ≥3-dose group. Three or more doses were associated with fewer LBW births (RR, 0.80; 95% CI, 0.69-0.94; I 2 = 0%), with a median LBW risk per 1000 women in the 2-dose group (assumed control group risk) of 167 per 1000 vs 134 per 1000 in the ≥3-dose group (absolute risk reduction, 33 per 1000 [95% CI, 10-52]; number needed to treat = 31). The association was consistent across a wide range of sulfadoxine-pyrimethamine resistance (0% to 96% dihydropteroate-synthase K540E mutations). There was no evidence of small-study bias. The ≥3-dose group had less placental malaria (RR, 0.51; 95% CI, 0.38-0.68; I 2 = 0%, in 6 trials, 63 vs 32 per 1000; absolute risk reduction, 31 per 1000 [95% CI, 20-39]). In primigravid plus secundigravid women, the risk of moderate to severe maternal anemia was lower in the ≥3-dose group (RR, 0.60; 95% CI, 0.36-0.99; I2 = 20%; in 6 trials, 36 vs 22 per 1000; absolute risk reduction, 14 per 1000 [95% CI, 0.4-23]). There were no differences in rates of serious adverse events.
CONCLUSIONS AND RELEVANCE
Among pregnant women in sub-Saharan Africa, intermittent preventive therapy with 3 or more doses of sulfadoxine-pyrimethamine was associated with a higher birth weight and lower risk of LBW than the standard 2-dose regimens. These data provide support for the new WHO recommendations to provide at least 3 doses of intermittent preventive therapy during pregnancy at each scheduled antenatal care visit in the second and third trimester.
Topics: Africa; Antimalarials; Drug Administration Schedule; Drug Combinations; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Malaria; Pregnancy; Pregnancy Complications, Infectious; Pyrimethamine; Risk; Sulfadoxine
PubMed: 23403684
DOI: 10.1001/jama.2012.216231 -
The Cochrane Database of Systematic... Jul 2021Intermittent preventive treatment could help prevent malaria in infants (IPTi) living in areas of moderate to high malaria transmission in sub-Saharan Africa. The World... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intermittent preventive treatment could help prevent malaria in infants (IPTi) living in areas of moderate to high malaria transmission in sub-Saharan Africa. The World Health Organization (WHO) policy recommended IPTi in 2010, but its adoption in countries has been limited.
OBJECTIVES
To evaluate the effects of intermittent preventive treatment (IPT) with antimalarial drugs to prevent malaria in infants living in malaria-endemic areas.
SEARCH METHODS
We searched the following sources up to 3 December 2018: the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE (PubMed), Embase (OVID), LILACS (Bireme), and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) and the WHO International Clinical Trials Registry Platform (ICTRP) portal for ongoing trials up to 3 December 2018.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that compared IPT to placebo or no intervention in infants (defined as young children aged between 1 to 12 months) in malaria-endemic areas.
DATA COLLECTION AND ANALYSIS
The primary outcome was clinical malaria (fever plus asexual parasitaemia). Two review authors independently assessed trials for inclusion, evaluated the risk of bias, and extracted data. We summarized dichotomous outcomes and count data using risk ratios (RR) and rate ratios respectively, and presented all measures with 95% confidence intervals (CIs). We extracted protective efficacy values and their 95% CIs; when an included trial did not report this data, we calculated these values from the RR or rate ratio with its 95% CI. Where appropriate, we combined data in meta-analyses and assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 12 trials that enrolled 19,098 infants; all were conducted in sub-Saharan Africa. Three trials were cluster-RCTs. IPTi with sulfadoxine-pyrimethamine (SP) was evaluated in 10 trials from 1999 to 2013 (n = 15,256). Trials evaluating ACTs included dihydroartemisinin-piperaquine (1 trial, 147 participants; year 2013), amodiaquine-artesunate (1 study, 684 participants; year 2008), and SP-artesunate (1 trial, 676 participants; year 2008). The earlier studies evaluated IPTi with SP, and were conducted in Tanzania (in 1999 and 2006), Mozambique (2004), Ghana (2004 to 2005), Gabon (2005), Kenya (2008), and Mali (2009). One trial evaluated IPTi with amodiaquine in Tanzania (2000). Later studies included three conducted in Kenya (2008), Tanzania (2008), and Uganda (2013), evaluating IPTi in multiple trial arms that included artemisinin-based combination therapy (ACT). Although the effect size varied over time and between drugs, overall IPTi impacts on the incidence of clinical malaria overall, with a 30% reduction (rate ratio 0.70, 0.62 to 0.80; 10 studies, 10,602 participants). The effect of SP appeared to attenuate over time, with trials conducted after 2009 showing little or no effect of the intervention. IPTi with SP probably resulted in fewer episodes of clinical malaria (rate ratio 0.78, 0.69 to 0.88; 8 trials, 8774 participants, moderate-certainty evidence), anaemia (rate ratio 0.82, 0.68 to 0.98; 6 trials, 7438 participants, moderate-certainty evidence), parasitaemia (rate ratio 0.66, 0.56 to 0.79; 1 trial, 1200 participants, moderate-certainty evidence), and fewer hospital admissions (rate ratio 0.85, 0.78 to 0.93; 7 trials, 7486 participants, moderate-certainty evidence). IPTi with SP probably made little or no difference to all-cause mortality (risk ratio 0.93, 0.74 to 1.15; 9 trials, 14,588 participants, moderate-certainty evidence). Since 2009, IPTi trials have evaluated ACTs and indicate impact on clinical malaria and parasitaemia. A small trial of DHAP in 2013 shows substantive effects on clinical malaria (RR 0.42, 0.33 to 0.54; 1 trial, 147 participants, moderate-certainty evidence) and parasitaemia (moderate-certainty evidence).
AUTHORS' CONCLUSIONS
In areas of sub-Saharan Africa, giving antimalarial drugs known to be effective against the malaria parasite at the time to infants as IPT probably reduces the risk of clinical malaria, anaemia, and hospital admission. Evidence from SP studies over a 19-year period shows declining efficacy, which may be due to increasing drug resistance. Combinations with ACTs appear promising as suitable alternatives for IPTi.
Topics: Africa South of the Sahara; Amodiaquine; Antimalarials; Artemisinins; Bias; Confidence Intervals; Disease Eradication; Drug Combinations; Endemic Diseases; Hospitalization; Humans; Infant; Malaria; Parasitemia; Pyrimethamine; Quinolines; Randomized Controlled Trials as Topic; Sulfadoxine
PubMed: 34273901
DOI: 10.1002/14651858.CD011525.pub3 -
Tropical Medicine & International... Dec 2015To estimate where intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) could be withdrawn as an intervention due to declining malaria... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To estimate where intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) could be withdrawn as an intervention due to declining malaria transmission intensity, or due to increasing prevalence of the Plasmodium falciparum dihydropteroate synthetase resistance mutation at codon 581G.
METHODS
We conducted a systematic review and meta-analysis of protection against the incidence of low birth weight (LBW) conferred by ≥2 doses of IPTp-SP. We matched these outcomes to a proxy measure of malaria incidence in women of the same studies, applied meta-regression models to these data and conducted sensitivity analysis of the 581G mutation.
RESULTS
Variation in the protective effect of IPTp-SP against LBW could not be explained by malaria transmission intensity. Among primi- and secundigravidae, IPTp-SP protected against LBW where 581G was ≤10.1% [odds ratio (OR): 0.49; 95% confidence intervals (CI): 0.29, 0.81; P = <0.01] and 581G was >10.1% (OR = 0.73; 95% CI: 0.29, 1.81; P = 0.03). Random-effects models among multigravidae showed that IPTp-SP protects against LBW where 581G was ≤10.1% (OR = 0.56; 95% CI: 0.37, 0.86; P = 0.07), a finding of borderline statistical significance. No evidence of protection against LBW was observed where 581G was >10.1% (OR = 0.96; 95% CI: 0.70, 1.34; P = 0.47).
CONCLUSION
There appears to be a prevalence of 581G above which IPTp-SP no longer protects against LBW. Pregnancy studies are urgently needed where 581G is >10.1% to define the specific prevalence threshold where new strategies should be deployed.
Topics: Africa South of the Sahara; Antimalarials; Dihydropteroate Synthase; Drug Combinations; Drug Resistance; Female; Gravidity; Humans; Infant, Low Birth Weight; Malaria, Falciparum; Mutation; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Sulfadoxine
PubMed: 26325263
DOI: 10.1111/tmi.12595 -
The American Journal of Tropical... Jan 2024Seasonal malaria chemoprevention (SMC) for children under 5 years of age for up to four monthly cycles during malaria transmission season was recommended by the WHO in... (Meta-Analysis)
Meta-Analysis
Seasonal malaria chemoprevention (SMC) for children under 5 years of age for up to four monthly cycles during malaria transmission season was recommended by the WHO in 2012 and has been implemented in 13 countries in the Sahel, reaching more than 30 million children annually. Malaria control programs implementing SMC have asked the WHO to consider expanding the age range or number of monthly cycles. We conducted a systematic review and meta-analysis of SMC among children up to 15 years of age and up to six monthly cycles. Twelve randomized studies were included, with outcomes stratified by age (< 5/≥ 5 years), by three or four versus five or six cycles, and by drug where possible. Drug regimens included sulfadoxine-pyrimethamine + amodiaquine, amodiaquine-artesunate, and sulfadoxine-pyrimethamine + artesunate. Included studies were all conducted in Sahelian countries in which high-grade resistance to sulfadoxine-pyrimethamine was rare and in zones with parasite prevalence ranging from 1% to 79%. Seasonal malaria chemoprevention resulted in substantial reductions in uncomplicated malaria incidence measured during that transmission season (rate ratio: 0.27, 95% CI: 0.25-0.29 among children < 5 years; rate ratio: 0.27, 95% CI: 0.25-0.30 among children ≥ 5 years) and in the prevalence of malaria parasitemia measured within 4-6 weeks from the final SMC cycle (risk ratio: 0.38, 95% CI: 0.34-0.43 among children < 5 years; risk ratio: 0.23, 95% CI: 0.11-0.48 among children ≥ 5 years). In high-transmission zones, SMC resulted in a moderately reduced risk of any anemia (risk ratio: 0.77, 95% CI: 0.72-0.83 among children < 5 years; risk ratio: 0.70, 95% CI: 0.52-0.95 among children ≥ 5 years [one study]). Children < 10 years of age had a moderate reduction in severe malaria (risk ratio: 0.53, 95% CI: 0.37-0.76) but no evidence of a mortality reduction. The evidence suggests that in areas in which sulfadoxine-pyrimethamine and amodiaquine remained efficacious, SMC effectively reduced malaria disease burden among children both < 5 and ≥ 5 years old and that the number of cycles should be commensurate with the length of the transmission season, up to six cycles.
Topics: Child; Child, Preschool; Humans; Amodiaquine; Antimalarials; Artesunate; Chemoprevention; Drug Combinations; Malaria; Pyrimethamine; Seasons; Sulfadoxine; Adolescent
PubMed: 38081050
DOI: 10.4269/ajtmh.23-0481 -
The Cochrane Database of Systematic... Jul 2021Haemolytic uraemic syndrome (HUS) is a common cause of acquired kidney failure in children and rarely in adults. The most important risk factor for development of HUS is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Haemolytic uraemic syndrome (HUS) is a common cause of acquired kidney failure in children and rarely in adults. The most important risk factor for development of HUS is a gastrointestinal infection by Shiga toxin-producing Escherichia coli (STEC). This review addressed the interventions aimed at secondary prevention of HUS in patients with diarrhoea who were infected with a bacteria that increase the risk of HUS.
OBJECTIVES
Our objective was to evaluate evidence regarding secondary preventative strategies for HUS associated with STEC infections. In doing so, we sought to assess the effectiveness and safety of interventions as well as their potential to impact the morbidity and death associated with this condition.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 12 November 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Studies were considered based on the methods, participants, and research goals. Only randomised controlled trials were considered eligible for inclusion. The participants of the studies were paediatric and adult patients with diarrhoeal illnesses due to STEC. The primary outcome of interest was incidence of HUS.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as recommended by Cochrane. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
We identified four studies (536 participants) for inclusion that investigated four different interventions including antibiotics (trimethoprim-sulfamethoxazole), anti-Shiga toxin antibody-containing bovine colostrum, Shiga toxin binding agent (Synsorb Pk: a silicon dioxide-based agent), and a monoclonal antibody against Shiga toxin (urtoxazumab). The overall risk of bias was unclear for selection, performance and detection bias and low for attrition, reporting and other sources of bias. It was uncertain if trimethoprim-sulfamethoxazole reduced the incidence of HUS compared to no treatment (47 participants: RR 0.57, 95% CI 0.11-2.81, very low certainty evidence). Adverse events relative to this review, need for acute dialysis, neurological complication and death were not reported. There were no incidences of HUS in either the bovine colostrum group or the placebo group. It was uncertain if bovine colostrum caused more adverse events (27 participants: RR 0.92, 95% CI 0.42 to 2.03; very low certainty evidence). The need for acute dialysis, neurological complications or death were not reported. It is uncertain whether Synsorb Pk reduces the incidence of HUS compared to placebo (353 participants: RR 0.93, 95% CI 0.39 to 2.22; very low certainty evidence). Adverse events relevant to this review, need for acute dialysis, neurological complications or death were not reported. One study compared two doses of urtoxazumab (3.0 mg/kg and 1.0 mg/kg) to placebo. It is uncertain if either 3.0 mg/kg urtoxazumab (71 participants: RR 0.34, 95% CI 0.01 to 8.14) or 1.0 mg/kg urtoxazumab (74 participants: RR 0.95, 95% CI 0.79 to 1.13) reduced the incidence of HUS compared to placebo (very low certainty evidence). Low certainty evidence showed there may be little or no difference in the number of treatment-emergent adverse events with either 3.0 mg/kg urtoxazumab (71 participants: RR 1.00, 95% CI 0.84 to 1.18) or 1.0 mg/kg urtoxazumab (74 participants: RR 0.95, 95% CI 0.79 to 1.13) compared to placebo. There were 25 serious adverse events reported in 18 patients: 10 in the placebo group, and 9 and 6 serious adverse events in the 1.0 mg/kg and 3.0 mg/kg urtoxazumab groups, respectively. It is unclear how many patients experienced these adverse events in each group, and how many patients experienced more than one event. It is uncertain if either dose of urtoxazumab increased the risk of neurological complications or death (very low certainty evidence). Need for acute dialysis was not reported.
AUTHORS' CONCLUSIONS
The included studies assessed antibiotics, bovine milk, and Shiga toxin inhibitor (Synsorb Pk) and monoclonal antibodies (Urtoxazumab) against Shiga toxin for secondary prevention of HUS in patients with diarrhoea due to STEC. However, no firm conclusions about the efficacy of these interventions can be drawn given the small number of included studies and the small sample sizes of those included studies. Additional studies, including larger multicentre studies, are needed to assess the efficacy of interventions to prevent development of HUS in patients with diarrhoea due to STEC infection.
Topics: Adult; Animals; Antibodies, Monoclonal, Humanized; Bias; Cattle; Child; Colostrum; Diarrhea; Escherichia coli Infections; Hemolytic-Uremic Syndrome; Humans; Incidence; Organosilicon Compounds; Placebos; Randomized Controlled Trials as Topic; Secondary Prevention; Shiga-Toxigenic Escherichia coli; Trimethoprim, Sulfamethoxazole Drug Combination; Trisaccharides
PubMed: 34219224
DOI: 10.1002/14651858.CD012997.pub2 -
The Cochrane Database of Systematic... 2001Intraventricular hemorrhage remains a serious complication of premature birth and post hemorrhagic hydrocephalus still has no satisfactory treatment. Acetazolamide and... (Review)
Review
BACKGROUND
Intraventricular hemorrhage remains a serious complication of premature birth and post hemorrhagic hydrocephalus still has no satisfactory treatment. Acetazolamide and furosemide, which both reduce the production of cerebrospinal fluid, have been suggested as non-invasive therapies to reduce hydrocephalus and the need for ventriculo-peritoneal (V-P) shunting.
OBJECTIVES
The aim of this review was to determine whether the use of acetazolamide and furosemide improves outcome, especially shunt dependence, in infants developing post-hemorrhagic ventricular dilatation.
SEARCH STRATEGY
The standard search strategy of the Cochrane Collaboration was used.
SELECTION CRITERIA
Randomised, or quasi-randomised trials, of acetazolamide and/or furosemide compared with standard therapy in infants with IVH or post-hemorrhagic ventricular dilatation
DATA COLLECTION AND ANALYSIS
Data were extracted independently by each author and were analysed by the standard methods of the Cochrane Collaboration using relative risk (RR) and risk difference (RD), a fixed effect model and sensitivity analyses where appropriate.
MAIN RESULTS
There were two eligible trials: one randomized 16 infants and the other, 177. Neither showed a decreased risk for V-P shunt or for V-P shunt or death associated with acetazolamide and furosemide therapy. The larger trial showed that acetazolamide and furosemide treatment resulted in a borderline increase in the risk for motor impairment at one year (RR 1.27, CI 1.02 to 1.58; RD 0.16, CI 0.02 to 0.31), but did not significantly affect the risk for the combined outcome of delay, disability or motor impairment among survivors, or the risk of the combined outcome of death, delay, disability or impairment at one year. The larger trial showed that diuretic treatment increased the risk for nephrocalcinosis (RR 5.31, CI 1.90 to 14.84; RD 0.19, CI 0.09 to 0.29); meta-analysis confirmed this result.
REVIEWER'S CONCLUSIONS
Acetazolamide and furosemide therapy is neither effective nor safe in treating post hemorrhagic ventricular dilatation. Acetazolamide and furosemide cannot be recommended as therapy for post hemorrhagic hydrocephalus.
Topics: Acetazolamide; Cerebral Hemorrhage; Cerebral Ventricles; Dilatation, Pathologic; Diuretics; Furosemide; Humans; Hydrocephalus; Infant; Infant, Newborn; Randomized Controlled Trials as Topic; Ventriculoperitoneal Shunt
PubMed: 11406041
DOI: 10.1002/14651858.CD002270 -
Antimicrobial Resistance and Infection... Apr 2022Vibrio cholerae O1/O139 were the predominant circulating serogroups exhibiting multi-drug resistance (MDR) during the cholera outbreak which led to cholera treatment... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vibrio cholerae O1/O139 were the predominant circulating serogroups exhibiting multi-drug resistance (MDR) during the cholera outbreak which led to cholera treatment failures.
OBJECTIVE
This meta-analysis aimed to evaluate the weighted pooled resistance (WPR) rates in V. cholerae O1/O139 isolates obtained from environmental samples.
METHODS
We systematically searched the articles in PubMed, Scopus, and Embase (until January 2020). Subgroup analyses were then employed by publication year, geographic areas, and the quality of studies. Statistical analyses were conducted using STATA software (ver. 14.0).
RESULTS
A total of 20 studies investigating 648 environmental V. cholerae O1/O139 isolates were analysed. The majority of the studies were originated from Asia (n = 9). In addition, a large number of studies (n = 15 i.e. 71.4%) included in the meta-analysis revealed the resistance to cotrimoxazole and ciprofloxacin. The WPR rates were as follows: cotrimoxazole 59%, erythromycin 28%, tetracycline 14%, doxycycline 5%, and ciprofloxacin 0%. There was increased resistance to nalidixic acid, cotrimoxazole, furazolidone, and tetracycline while a decreased resistance to amoxicillin, ciprofloxacin, erythromycin, chloramphenicol, ampicillin, streptomycin, and ceftriaxone was observed during the years 2000-2020. A significant decrease in the doxycycline and ciprofloxacin-resistance rates in V. cholerae O1/O139 isolates was reported over the years 2011-2020 which represents a decrease in 2001-2010 (p < 0.05).
CONCLUSIONS
Fluoroquinolones, gentamicin, ceftriaxone, doxycycline, kanamycin, and cefotaxime showed the highest effectiveness and the lowest resistance rate. However, the main interest is the rise of antimicrobial resistance in V. cholerae strains especially in low-income countries or endemic areas, and therefore, continuous surveillance, careful appropriate AST, and limitation on improper antibiotic usage are crucial.
Topics: Anti-Bacterial Agents; Ceftriaxone; Cholera; Ciprofloxacin; Doxycycline; Drug Resistance, Bacterial; Erythromycin; Humans; Microbial Sensitivity Tests; Trimethoprim, Sulfamethoxazole Drug Combination; Vibrio cholerae O1; Vibrio cholerae O139
PubMed: 35468830
DOI: 10.1186/s13756-022-01100-3