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International Journal of Environmental... Oct 2022There are several techniques for the removal of pharmaceuticals (drugs) from wastewater; however, strengths and weaknesses have been observed in their elimination... (Review)
Review
There are several techniques for the removal of pharmaceuticals (drugs) from wastewater; however, strengths and weaknesses have been observed in their elimination processes that limit their applicability. Therefore, we aimed to evaluate the best techniques for the removal of pharmaceuticals from municipal and hospital wastewater. For this, a non-experimental, descriptive, qualitative-quantitative design was used, corresponding to a systematic review without meta-analysis. Based on established inclusion and exclusion criteria, 31 open-access articles were selected from the Scopus, ProQuest, EBSCOhost, and ScienceDirect databases. The results showed that high concentrations of analgesics such as naproxen (1.37 mg/L) and antibiotics such as norfloxacin (0.561 mg/L) are frequently found in wastewater and that techniques such as reverse osmosis, ozonation, and activated sludge have the best removal efficiency, achieving values of 99%. It was concluded that reverse osmosis is one of the most efficient techniques for eliminating ofloxacin, sulfamethoxazole, carbamazepine, and diclofenac from municipal wastewater, with removal rates ranging from 96 to 99.9%, while for hospital wastewater the activated sludge technique proved to be efficient, eliminating analgesics and antibiotics in the range of 41-99%.
Topics: Wastewater; Sewage; Diclofenac; Naproxen; Norfloxacin; Water Pollutants, Chemical; Carbamazepine; Hospitals; Ozone; Sulfamethoxazole; Anti-Bacterial Agents; Ofloxacin; Pharmaceutical Preparations; Waste Disposal, Fluid
PubMed: 36293682
DOI: 10.3390/ijerph192013105 -
Pediatric Pulmonology May 2023Cepacia syndrome (CS) is an acute, necrotizing pneumonia with a high mortality rate, occurring in patients with cystic fibrosis (CF) infected with Burkholderia cepacia... (Review)
Review
BACKGROUND
Cepacia syndrome (CS) is an acute, necrotizing pneumonia with a high mortality rate, occurring in patients with cystic fibrosis (CF) infected with Burkholderia cepacia complex (BCC). Due to its low incidence, data on this condition are limited.
METHODS
We conducted a systematic review of the reported cases of CS by searching MEDLINE, Embase and the Cochrane Library to improve knowledge of this rare but potentially lethal condition.
RESULTS
We included 15 eligible articles, describing 18 cases (9 females) of CS. Median age at onset was 22 years (range: 10-60 years); median time to CS after first infection by BCC was 5 years (range: 1-26 years). Burkholderia cenocepacia was the most frequently reported causative agent. All patients received intravenous antibiotic treatment (most frequently including cotrimoxazole), while inhaled antibiotics were used in five patients (27.8%). Immunosuppressant agents were the most commonly prescribed supportive treatment (n = 7, 38.9%). Half of the patients died (9/18, 50%).
CONCLUSIONS
This study describes epidemiological, clinical characteristics, and prognosis of CS cases reported over the last 24 years. CS is a rare yet severe complication of BCC infection in patients with CF, which occurs several years after BCC colonization and has a negative outcome in 50% of the patients. Data are too scanty to identify the most effective therapeutic approach.
Topics: Female; Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Cystic Fibrosis; Anti-Bacterial Agents; Burkholderia cepacia complex; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination; Burkholderia Infections
PubMed: 36815622
DOI: 10.1002/ppul.26359 -
The Cochrane Database of Systematic... Mar 2018The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for malaria for all women who live in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for malaria for all women who live in moderate to high malaria transmission areas in Africa. However, parasite resistance to sulfadoxine-pyrimethamine has been increasing steadily in some areas of the region. Moreover, HIV-infected women on cotrimoxazole prophylaxis cannot receive sulfadoxine-pyrimethamine because of potential drug interactions. Thus, there is an urgent need to identify alternative drugs for prevention of malaria in pregnancy. One such candidate is mefloquine.
OBJECTIVES
To assess the effects of mefloquine for preventing malaria in pregnant women, specifically, to evaluate:• the efficacy, safety, and tolerability of mefloquine for preventing malaria in pregnant women; and• the impact of HIV status, gravidity, and use of insecticide-treated nets on the effects of mefloquine.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), the Malaria in Pregnancy Library, and two trial registers up to 31 January 2018. In addition, we checked references and contacted study authors to identify additional studies, unpublished data, confidential reports, and raw data from published trials.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials comparing mefloquine IPT or mefloquine prophylaxis against placebo, no treatment, or an alternative drug regimen.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when required. Dichotomous outcomes were compared using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes using mean differences (MDs). We have presented all measures of effect with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach for the following main outcomes of analysis: maternal peripheral parasitaemia at delivery, clinical malaria episodes during pregnancy, placental malaria, maternal anaemia at delivery, low birth weight, spontaneous abortions and stillbirths, dizziness, and vomiting.
MAIN RESULTS
Six trials conducted between 1987 and 2013 from Thailand (1), Benin (3), Gabon (1), Tanzania (1), Mozambique (2), and Kenya (1) that included 8192 pregnant women met our inclusion criteria.Two trials (with 6350 HIV-uninfected pregnant women) compared two IPTp doses of mefloquine with two IPTp doses of sulfadoxine-pyrimethamine. Two other trials involving 1363 HIV-infected women compared three IPTp doses of mefloquine plus cotrimoxazole with cotrimoxazole. One trial in 140 HIV-infected women compared three doses of IPTp-mefloquine with cotrimoxazole. Finally, one trial enrolling 339 of unknown HIV status compared mefloquine prophylaxis with placebo.Study participants included women of all gravidities and of all ages (four trials) or > 18 years (two trials). Gestational age at recruitment was > 20 weeks (one trial), between 16 and 28 weeks (three trials), or ≤ 28 weeks (two trials). Two of the six trials blinded participants and personnel, and only one had low risk of detection bias for safety outcomes.When compared with sulfadoxine-pyrimethamine, IPTp-mefloquine results in a 35% reduction in maternal peripheral parasitaemia at delivery (RR 0.65, 95% CI 0.48 to 0.86; 5455 participants, 2 studies; high-certainty evidence) but may have little or no effect on placental malaria infections (RR 1.04, 95% CI 0.58 to 1.86; 4668 participants, 2 studies; low-certainty evidence). Mefloquine results in little or no difference in the incidence of clinical malaria episodes during pregnancy (incidence rate ratio (IRR) 0.83, 95% CI 0.65 to 1.05, 2 studies; high-certainty evidence). Mefloquine decreased maternal anaemia at delivery (RR 0.84, 95% CI 0.76 to 0.94; 5469 participants, 2 studies; moderate-certainty evidence). Data show little or no difference in the proportions of low birth weight infants (RR 0.95, 95% CI 0.78 to 1.17; 5641 participants, 2 studies; high-certainty evidence) and in stillbirth and spontaneous abortion rates (RR 1.20, 95% CI 0.91 to 1.58; 6219 participants, 2 studies; I statistic = 0%; high-certainty evidence). IPTp-mefloquine increased drug-related vomiting (RR 4.76, 95% CI 4.13 to 5.49; 6272 participants, 2 studies; high-certainty evidence) and dizziness (RR 4.21, 95% CI 3.36 to 5.27; participants = 6272, 2 studies; high-certainty evidence).When compared with cotrimoxazole, IPTp-mefloquine plus cotrimoxazole probably results in a 48% reduction in maternal peripheral parasitaemia at delivery (RR 0.52, 95% CI 0.30 to 0.93; 989 participants, 2 studies; moderate-certainty evidence) and a 72% reduction in placental malaria (RR 0.28, 95% CI 0.14 to 0.57; 977 participants, 2 studies; high-certainty evidence) but has little or no effect on the incidence of clinical malaria episodes during pregnancy (IRR 0.76, 95% CI 0.33 to 1.76, 1 study; high-certainty evidence) and probably no effect on maternal anaemia at delivery (RR 0.94, 95% CI 0.73 to 1.20; 1197 participants, 2 studies; moderate-certainty evidence), low birth weight rates (RR 1.20, 95% CI 0.89 to 1.60; 1220 participants, 2 studies; moderate-certainty evidence), and rates of spontaneous abortion and stillbirth (RR 1.12, 95% CI 0.42 to 2.98; 1347 participants, 2 studies; very low-certainty evidence). Mefloquine was associated with higher risks of drug-related vomiting (RR 7.95, 95% CI 4.79 to 13.18; 1055 participants, one study; high-certainty evidence) and dizziness (RR 3.94, 95% CI 2.85 to 5.46; 1055 participants, 1 study; high-certainty evidence).
AUTHORS' CONCLUSIONS
Mefloquine was more efficacious than sulfadoxine-pyrimethamine in HIV-uninfected women or daily cotrimoxazole prophylaxis in HIV-infected pregnant women for prevention of malaria infection and was associated with lower risk of maternal anaemia, no adverse effects on pregnancy outcomes (such as stillbirths and abortions), and no effects on low birth weight and prematurity. However, the high proportion of mefloquine-related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women.
Topics: Abortion, Spontaneous; Africa South of the Sahara; Antimalarials; Dizziness; Drug Combinations; Drug Therapy, Combination; Female; HIV Infections; Humans; Infant, Low Birth Weight; Insecticide-Treated Bednets; Malaria; Mefloquine; Parasitemia; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Randomized Controlled Trials as Topic; Sulfadoxine; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination; Vomiting
PubMed: 29561063
DOI: 10.1002/14651858.CD011444.pub2 -
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 Cochrane Database of Systematic... Aug 2018Buruli ulcer is a necrotizing cutaneous infection caused by infection with Mycobacterium ulcerans bacteria that occurs mainly in tropical and subtropical regions. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Buruli ulcer is a necrotizing cutaneous infection caused by infection with Mycobacterium ulcerans bacteria that occurs mainly in tropical and subtropical regions. The infection progresses from nodules under the skin to deep ulcers, often on the upper and lower limbs or on the face. If left undiagnosed and untreated, it can lead to lifelong disfigurement and disabilities. It is often treated with drugs and surgery.
OBJECTIVES
To summarize the evidence of drug treatments for treating Buruli ulcer.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (Ovid); and LILACS (Latin American and Caribbean Health Sciences Literature; BIREME). We also searched the US National Institutes of Health Ongoing Trials Register (clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en/). All searches were run up to 19 December 2017. We also checked the reference lists of articles identified by the literature search, and contacted leading researchers in this topic area to identify any unpublished data.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that compared antibiotic therapy to placebo or alternative therapy such as surgery, or that compared different antibiotic regimens. We also included prospective observational studies that evaluated different antibiotic regimens with or without surgery.
DATA COLLECTION AND ANALYSIS
Two review authors independently applied the inclusion criteria, extracted the data, and assessed methodological quality. We calculated the risk ratio (RR) for dichotomous data with 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included a total of 18 studies: five RCTs involving a total of 319 participants, ranging from 12 participants to 151 participants, and 13 prospective observational studies, with 1665 participants. Studies evaluated various drugs usually in addition to surgery, and were carried out across eight countries in areas with high Buruli ulcer endemicity in West Africa and Australia. Only one RCT reported adequate methods to minimize bias. Regarding monotherapy, one RCT and one observational study evaluated clofazimine, and one RCT evaluated sulfamethoxazole/trimethoprim. All three studies had small sample sizes, and no treatment effect was demonstrated. The remaining studies examined combination therapy.Rifampicin combined with streptomycinWe found one RCT and six observational studies which evaluated rifampicin combined with streptomycin for different lengths of treatment (2, 4, 8, or 12 weeks) (941 participants). The RCT did not demonstrate a difference between the drugs added to surgery compared with surgery alone for recurrence at 12 months, but was underpowered (RR 0.12, 95% CI 0.01 to 2.51; 21 participants; very low-certainty evidence).An additional five single-arm observational studies with 828 participants using this regimen for eight weeks with surgery (given to either all participants or to a select group) reported healing rates ranging from 84.5% to 100%, assessed between six weeks and one year. Four observational studies reported healing rates for participants who received the regimen alone without surgery, reporting healing rates ranging from 48% to 95% assessed between eight weeks and one year.Rifampicin combined with clarithromycinTwo observational studies administered combined rifampicin and clarithromycin. One study evaluated the regimen alone (no surgery) for eight weeks and reported a healing rate of 50% at 12 months (30 participants). Another study evaluated the regimen administered for various durations (as determined by the clinicians, durations unspecified) with surgery and reported a healing rate of 100% at 12 months (21 participants).Rifampicin with streptomycin initially, changing to rifampicin with clarithromycin in consolidation phaseOne RCT evaluated this regimen (four weeks in each phase) against continuing with rifampicin and streptomycin in the consolidation phase (total eight weeks). All included participants had small lesions, and healing rates were above 90% in both groups without surgery (healing rate at 12 months RR 0.94, 95% CI 0.87 to 1.03; 151 participants; low-certainty evidence). One single-arm observational study evaluating the substitution of streptomycin with clarithromycin in the consolidation phase (6 weeks, total 8 weeks) without surgery given to a select group showed a healing rate of 98% at 12 months (41 participants).Novel combination therapyTwo large prospective studies in Australia evaluated some novel regimens. One study evaluating rifampicin combined with either ciprofloxacin, clarithromycin, or moxifloxacin without surgery reported a healing rate of 76.5% at 12 months (132 participants). Another study evaluating combinations of two to three drugs from rifampicin, ciprofloxacin, clarithromycin, ethambutol, moxifloxacin, or amikacin with surgery reported a healing rate of 100% (90 participants).Adverse effects were reported in only three RCTs (158 participants) and eight prospective observational studies (878 participants), and were consistent with what is already known about the adverse effect profile of these drugs. Paradoxical reactions (clinical deterioration after treatment caused by enhanced immune response to M ulcerans) were evaluated in six prospective observational studies (822 participants), and the incidence of paradoxical reactions ranged from 1.9% to 26%.
AUTHORS' CONCLUSIONS
While the antibiotic combination treatments evaluated appear to be effective, we found insufficient evidence showing that any particular drug is more effective than another. How different sizes, lesions, and stages of the disease may contribute to healing and which kind of lesions are in need of surgery are unclear based on the included studies. Guideline development needs to consider these factors in designing practical treatment regimens. Forthcoming trials using clarithromycin with rifampicin and other trials of new regimens that also address these factors will help to identify the best regimens.
Topics: Anti-Bacterial Agents; Buruli Ulcer; Clarithromycin; Clofazimine; Drug Therapy, Combination; Humans; Mycobacterium ulcerans; Observational Studies as Topic; Randomized Controlled Trials as Topic; Rifampin; Streptomycin; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 30136733
DOI: 10.1002/14651858.CD012118.pub2 -
The Cochrane Database of Systematic... Mar 2016Following surgery, incisions are usually closed by fixing the edges together with sutures (stitches), staples, adhesives (glue) or clips. This process helps the cut... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Following surgery, incisions are usually closed by fixing the edges together with sutures (stitches), staples, adhesives (glue) or clips. This process helps the cut edges heal together and is called 'healing by primary intention'. However, a minority of surgical wounds are not closed in this way. Where the risk of infection is high or there has been significant loss of tissue, wounds may be left open to heal by the growth of new tissue rather than by primary closure; this is known as 'healing by secondary intention'. There is a risk of infection in open wounds, which may impact on wound healing, and antiseptic or antibiotic treatments may be used with the aim of preventing or treating such infections. This review is one of a suite of Cochrane reviews investigating the evidence on antiseptics and antibiotics in different types of wounds. It aims to present current evidence related to the use of antiseptics and antibiotics for surgical wounds healing by secondary intention (SWHSI).
OBJECTIVES
To assess the effects of systemic and topical antibiotics, and topical antiseptics for the treatment of surgical wounds healing by secondary intention.
SEARCH METHODS
In November 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We also searched three clinical trials registries and the references of included studies and relevant systematic reviews. There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA
Randomised controlled trials which enrolled adults with a surgical wound healing by secondary intention and assessed treatment with an antiseptic or antibiotic treatment. Studies enrolling people with skin graft donor sites were not included, neither were studies of wounds with a non-surgical origin which had subsequently undergone sharp or surgical debridement or other surgical treatments or wounds within the oral or aural cavities.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, risk of bias assessment and data extraction.
MAIN RESULTS
Eleven studies with a total of 886 participants were included in the review. These evaluated a range of comparisons in a range of surgical wounds healing by secondary intention. In general studies were small and some did not present data or analyses that could be easily interpreted or related to clinical outcomes. These factors reduced the quality of the evidence.Two comparisons compared different iodine preparations with no antiseptic treatment and found no clear evidence of effects for these treatments. The outcome data available were limited and what evidence there was low quality.One study compared a zinc oxide mesh dressing with a plain mesh dressing. There was no clear evidence of a difference in time to wound healing between groups. There was some evidence of a difference in measures used to assess wound infection (wound with foul smell and number of participants prescribed antibiotics) which favoured the zinc oxide group. This was low quality evidence.One study reported that sucralfate cream increased the likelihood of healing open wounds following haemorrhoidectomy compared to a petrolatum cream (RR: 1.50, 95% CI 1.13 to 1.99) over a three week period. This evidence was graded as being of moderate quality. The study also reported lower wound pain scores in the sucralfate group.There was a reduction in time to healing of open wounds following haemorrhoidectomy when treated with Triclosan post-operatively compared with a standard sodium hypochlorite solution (mean difference -1.70 days, 95% CI -3.41 to 0.01). This was classed as low quality evidence.There was moderate quality evidence that more open wounds resulting from excision of pyomyositis abscesses healed when treated with a honey-soaked gauze compared with a EUSOL-soaked gauze over three weeks' follow-up (RR: 1.58, 95% CI 1.03 to 2.42). There was also some evidence of a reduction in the mean length of hospital stay in the honey group. Evidence was taken from one small study that only had 43 participants.There was moderate quality evidence that more Dermacym®-treated post-operative foot wounds in people with diabetes healed compared to those treated with iodine (RR 0.61, 95% CI 0.40 to 0.93). Again estimates came from one small study with 40 participants.
AUTHORS' CONCLUSIONS
There is no robust evidence on the relative effectiveness of any antiseptic/antibiotic/anti-bacterial preparation evaluated to date for use on SWHSI. Where some evidence for possible treatment effects was reported, it stemmed from single studies with small participant numbers and was classed as moderate or low quality evidence. This means it is likely or very likely that further research will have an important impact on our confidence in the estimate of effect, and may change this estimate.
Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Humans; Iodine; Randomized Controlled Trials as Topic; Sucralfate; Surgical Mesh; Surgical Procedures, Operative; Surgical Wound Infection; Trimethoprim, Sulfamethoxazole Drug Combination; Wound Healing; Zinc Oxide
PubMed: 27021482
DOI: 10.1002/14651858.CD011712.pub2 -
The Lancet. Infectious Diseases Aug 2020Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum... (Meta-Analysis)
Meta-Analysis
Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: a systematic review and individual patient data meta-analysis.
BACKGROUND
Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy and tolerability of different artemisinin-based or quinine-based treatments for malaria in pregnant women.
METHODS
We did a systematic review of interventional or observational cohort studies assessing the efficacy of artemisinin-based or quinine-based treatments in pregnancy. Seven databases (MEDLINE, Embase, Global Health, Cochrane Library, Scopus, Web of Science, and Literatura Latino Americana em Ciencias da Saude) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrials.gov) were searched. The final search was done on April 26, 2019. Studies that assessed PCR-corrected treatment efficacy in pregnancy with follow-up of 28 days or more were included. Investigators of identified studies were invited to share data from individual patients. The outcomes assessed included PCR-corrected efficacy, PCR-uncorrected efficacy, parasite clearance, fever clearance, gametocyte development, and acute adverse events. One-stage IPD meta-analysis using Cox and logistic regression with random-effects was done to estimate the risk factors associated with PCR-corrected treatment failure, using artemether-lumefantrine as the reference. This study is registered with PROSPERO, CRD42018104013.
FINDINGS
Of the 30 studies assessed, 19 were included, representing 92% of patients in the literature (4968 of 5360 episodes). Risk of PCR-corrected treatment failure was higher for the quinine monotherapy (n=244, adjusted hazard ratio [aHR] 6·11, 95% CI 2·57-14·54, p<0·0001) but lower for artesunate-amodiaquine (n=840, 0·27, 95% 0·14-0·52, p<0·0001), artesunate-mefloquine (n=1028, 0·56, 95% 0·34-0·94, p=0·03), and dihydroartemisinin-piperaquine (n=872, 0·35, 95% CI 0·18-0·68, p=0·002) than artemether-lumefantrine (n=1278) after adjustment for baseline asexual parasitaemia and parity. The risk of gametocyte carriage on day 7 was higher after quinine-based therapy than artemisinin-based treatment (adjusted odds ratio [OR] 7·38, 95% CI 2·29-23·82).
INTERPRETATION
Efficacy and tolerability of artemisinin-based combination therapies (ACTs) in pregnant women are better than quinine. The lower efficacy of artemether-lumefantrine compared with other ACTs might require dose optimisation.
FUNDING
The Bill & Melinda Gates Foundation, ExxonMobil Foundation, and the University of Oxford Clarendon Fund.
Topics: Amodiaquine; Anti-Bacterial Agents; Antimalarials; Artemisinins; Artesunate; Atovaquone; Clindamycin; Drug Combinations; Drug Therapy, Combination; Female; Humans; Malaria, Falciparum; Mefloquine; Pregnancy; Pregnancy Complications, Parasitic; Proguanil; Pyrimethamine; Quinine; Quinolines; Sulfadoxine
PubMed: 32530424
DOI: 10.1016/S1473-3099(20)30064-5 -
International Journal of Antimicrobial... Jul 2021Antibiotic consumption is a key driver of antimicrobial resistance (AR), particularly in low- and middle-income countries (LMICs) where risk factors for AR emergence and...
Antibiotic consumption is a key driver of antimicrobial resistance (AR), particularly in low- and middle-income countries (LMICs) where risk factors for AR emergence and spread are prevalent. However, the potential contribution of mass drug administration (MDA) and systematic drug administration (SDA) of antibiotics to AR spread is unknown. We conducted a systematic review to provide an overview of MDA/SDA in LMICs, including indications, antibiotics used and, if investigated, levels of AR over time. This systematic review is reported in accordance with the PRISMA statement. Of 2438 identified articles, 63 were reviewed: indications for MDA/SDA were various, and targeted populations were particularly vulnerable, including pregnant women, children, human immunodeficiency virus (HIV)-infected populations, and communities in outbreak settings. Available data suggest that MDA/SDA may lead to a significant increase in AR, especially following azithromycin administration. However, only 40% of studies evaluated AR. Integrative approaches that evaluate AR in addition to clinical outcomes are needed to understand the consequences of MDA/SDA implementation, combined with standardised AR surveillance for timely detection of AR emergence.
Topics: Amoxicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Ciprofloxacin; Developing Countries; Doxycycline; Drug Resistance, Microbial; Drug Utilization; Female; Humans; Mass Drug Administration; Pregnancy; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 34044108
DOI: 10.1016/j.ijantimicag.2021.106364 -
Pharmacotherapy Nov 2022Patients with inflammatory bowel disease (IBD) are at increased risk of developing Pneumocystis jirovecii pneumonia (PJP) than the general population. Many medications... (Review)
Review
Patients with inflammatory bowel disease (IBD) are at increased risk of developing Pneumocystis jirovecii pneumonia (PJP) than the general population. Many medications utilized for the treatment of IBD affect the immune system, potentially further increasing the risk of PJP. Recommendations for prophylaxis against PJP in this patient population are based upon limited evidence, and risk factors for PJP development are not well-agreed upon. The purpose of this systematic review was to consolidate and evaluate the evidence for PJP prophylaxis in patients with IBD. An electronic literature search was performed, and 29 studies were included in the review, of which 24 were case reports or case series. Combined data from five cohort studies showed an absolute risk of developing PJP to be 0.07%. The majority of patients who developed PJP were receiving corticosteroids at the time of diagnosis (76%). The number of concomitant immunosuppressants received at time of PJP diagnosis varied from one to four. All studies reporting treatment of PJP utilized sulfamethoxazole-trimethoprim. Of the 27 studies reporting mortality data, 19% of patients died. Given the lack of conclusive data regarding risk factors for PJP development and the overall low incidence of PJP in patients with IBD, it is recommended to assess the patient's risk on a case-by-case basis to determine whether PJP prophylaxis is warranted.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination; Inflammatory Bowel Diseases; Immunosuppressive Agents
PubMed: 36222368
DOI: 10.1002/phar.2733 -
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