-
Frontiers in Endocrinology 2023Hypoglycemia is a sporadic and serious adverse reaction of trimethoprim-sulfamethoxazole (TMP-SMX) due to its sulfonylurea-like effect. This study explored the clinical...
OBJECTIVE
Hypoglycemia is a sporadic and serious adverse reaction of trimethoprim-sulfamethoxazole (TMP-SMX) due to its sulfonylurea-like effect. This study explored the clinical characteristics, risk factors, treatment, and prognosis of TMP-SMX-induced hypoglycemia.
METHODS
Case reports and series of TMP-SMX-induced hypoglycemia were systematically searched using Chinese and English databases. Primary patient and clinical information were extracted for analysis.
RESULTS
A total of 34 patients were reported from 31 studies (16 males and 18 females). The patients had a median age of 64 years (range 0.4-91), and 75.8% had renal dysfunction. The median duration of a hypoglycemic episode was six days (range 1-20), and the median minimum glucose was 28.8 mg/dL (range 12-60). Thirty-two patients (97.0%) showed neuroglycopenic symptoms, with consciousness disturbance (30.3%) and seizure (24.2%), sweating (18.2%), confusion (15.2%), asthenia (12.1%) being the most common symptoms. Fifteen patients (44.1%) had elevated serum insulin levels, with a median of 31.8 μU/mL (range 3-115.3). C-peptide increased in 13 patients (38.2%), with a median of 7.7 ng/mL (range 2.2-20). Complete recovery from symptoms occurred in 88.2% of patients without sequelae. The duration of hypoglycemia symptoms was 8 hours to 47 days after the intervention. Interventions included discontinuation of TMP-SMX, intravenous glucose, glucagon, and octreotide.
CONCLUSION
Hypoglycemia is a rare and serious adverse effect of TMP-SMX. Physicians should be aware of this potential adverse effect, especially in patients with renal insufficiency, increased drug doses, and malnutrition.
Topics: Male; Female; Humans; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Trimethoprim, Sulfamethoxazole Drug Combination; Risk Factors; Hypoglycemia; Renal Insufficiency; Glucose
PubMed: 36843590
DOI: 10.3389/fendo.2023.1059522 -
Medicine Sep 2016The aim of this study is to determine the prevalence of antibiotic susceptibility and resistance of Escherichia coli Escherichia coli (E coli) in female uncomplicated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The aim of this study is to determine the prevalence of antibiotic susceptibility and resistance of Escherichia coli Escherichia coli (E coli) in female uncomplicated cystitis in Korea using meta-analysis.
METHODS
A cross-search of the literature was performed with MEDLINE for all relevant data published before October 2015 and EMBASE from 1980 to 2015, the Cochrane Library, KoreaMed, RISS, KISS, and DBPia were also searched. Observational or prospective studies that reported the prevalence of antimicrobial susceptibility and resistance of E coli were selected for inclusion. No language or time restrictions were applied. We performed a meta-analysis using a random effects model to quantify the prevalence of antimicrobial susceptibility and resistance of E coli.
RESULTS
Ten studies were eligible for the meta-analysis, which together included a total of 2305 women with uncomplicated cystitis. The overall resistance rate to antibiotics was 0.28 (95% confidence interval [CI]: 0.25, 0.32). The pooled resistance rates were 0.08 (95% CI: 0.06, 0.11) for cephalosporin, 0.22 (95% CI: 0.18, 0.25) for fluoroquinolone (FQ), and 0.43 (95% CI: 0.35, 0.51) for trimethoprim/sulfamethoxazole (TMP/SMX). Regression analysis showed that resistance to FQ is increasing (P = 0.014) and resistance to TMP/SMX is decreasing (P = 0.043) by year. The generation of cephalosporin was not a significant moderator of differences in resistance rate.
CONCLUSION
The resistance rate of FQ in Korea is over 20% and is gradually increasing. Although the resistance rate of TMP/SMX is over 40%, its tendency is in decreasing state. Antibiotic strategies used for the treatment of uncomplicated cystitis in Korea have to be modified.
Topics: Cystitis; Drug Combinations; Drug Resistance, Bacterial; Escherichia coli; Fluoroquinolones; Humans; Republic of Korea; Sulfamethizole; Trimethoprim
PubMed: 27603359
DOI: 10.1097/MD.0000000000004663 -
Clinical Microbiology and Infection :... Feb 2024Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial. (Meta-Analysis)
Meta-Analysis Review
Trimethoprim-sulfamethoxazole significantly reduces the risk of nocardiosis in solid organ transplant recipients: systematic review and individual patient data meta-analysis.
BACKGROUND
Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial.
OBJECTIVES
To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection.
METHODS
A systematic review and individual patient data meta-analysis.
DATA SOURCES
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023.
STUDY ELIGIBILITY CRITERIA
(a) Risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (b) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis.
PARTICIPANTS
SOT recipients.
INTERVENTION
TMP-SMX prophylaxis versus no prophylaxis.
ASSESSMENT OF RISK OF BIAS
Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies.
METHODS OF DATA SYNTHESIS
For our primary outcome (i.e. to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis and 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92-100).
CONCLUSIONS
In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection.
Topics: Humans; Breakthrough Infections; Nocardia Infections; Organ Transplantation; Retrospective Studies; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 37865337
DOI: 10.1016/j.cmi.2023.10.008 -
Journal of Infection and Public Health 2018Evidence to demonstrate the prevalence and trend of Methicillin Resistant Staphylococcus aureus (MRSA) infection in Nigeria is scarce. This review evaluates the... (Review)
Review
BACKGROUND
Evidence to demonstrate the prevalence and trend of Methicillin Resistant Staphylococcus aureus (MRSA) infection in Nigeria is scarce. This review evaluates the prevalence, trend and antimicrobial susceptibility of clinical MRSA isolates reported in published studies.
METHOD
Electronic search (PubMed, Scopus and Google scholar) was conducted using the following search terms: "MRSA OR Methicillin Resistant Staphylococcus aureus AND Nigeria." Reference list of selected studies was scanned to identify more studies. Studies published between 2007 and 2017 that tested at least 30 non-duplicate S. aureus isolates were selected. An independent reviewer extracted data from the studies using a standardized form.
RESULTS
Twelve studies were included in this review. Overall, prevalence of MRSA infection increased from 18.3% (2009) to 42.3% (2013). The prevalence of MRSA infection was less than 50% in all the regions during the period under review. There was a decline in the prevalence of MRSA infection in the North-East (from 12.5% to 8.0%) between 2007 and 2012, and an increase in the South-West (from 20.2% to 47.4%) between 2006 and 2010. Wound, blood and urine specimens had the highest proportion of MRSA isolates. Non-susceptibility of MRSA strains to cotrimoxazole and tetracycline was greater than 85%.
CONCLUSION
Prevalence of MRSA infection in Nigeria is rising, albeit regional variations. Non-susceptibility to commonly prescribed, orally available and inexpensive antibiotics was high. Antimicrobial resistance surveillance system, infection control, and antimicrobial stewardship interventions are recommended.
Topics: Anti-Bacterial Agents; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Nigeria; Prevalence; Staphylococcal Infections; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 29933910
DOI: 10.1016/j.jiph.2018.05.013 -
The Cochrane Database of Systematic... Feb 2018The 8-aminoquinoline (8AQ) drugs act on Plasmodium falciparum gametocytes, which transmit malaria from infected people to mosquitoes. In 2012, the World Health... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The 8-aminoquinoline (8AQ) drugs act on Plasmodium falciparum gametocytes, which transmit malaria from infected people to mosquitoes. In 2012, the World Health Organization (WHO) recommended a single dose of 0.25 mg/kg primaquine (PQ) be added to malaria treatment schedules in low-transmission areas or those with artemisinin resistance. This replaced the previous recommendation of 0.75 mg/kg, aiming to reduce haemolysis risk in people with glucose-6-phosphate dehydrogenase deficiency, common in people living in malarious areas. Whether this approach, and at this dose, is effective in reducing transmission is not clear.
OBJECTIVES
To assess the effects of single dose or short-course PQ (or an alternative 8AQ) alongside treatment for people with P. falciparum malaria.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; and the WHO International Clinical Trials Registry Platform (ICRTP) portal using 'malaria*', 'falciparum', 'primaquine', '8-aminoquinoline', and eight 8AQ drug names as search terms. We checked reference lists of included trials, and contacted researchers and organizations. Date of last search: 21 July 2017.
SELECTION CRITERIA
Randomized controlled trials (RCTs) or quasi-RCTs in children or adults, adding PQ (or alternative 8AQ) as a single dose or short course alongside treatment for P. falciparum malaria.
DATA COLLECTION AND ANALYSIS
Two authors screened abstracts, applied inclusion criteria, and extracted data. We sought evidence on transmission (community incidence), infectiousness (people infectious and mosquitoes infected), and potential infectiousness (gametocyte measures assessed by microscopy or polymerase chain reaction [PCR]). We grouped trials into artemisinin and non-artemisinin treatments, and stratified by PQ dose (low, 0.2 to 0.25 mg/kg; moderate, 0.4 to 0.5 mg/kg; high, 0.75 mg/kg). We used GRADE, and absolute effects of infectiousness using trial control groups.
MAIN RESULTS
We included 24 RCTs and one quasi-RCT, comprising 43 arms. Fourteen trials evaluated artemisinin treatments (23 arms), nine trials evaluated non-artemisinin treatments (13 arms), and two trials included both artemisinin and non-artemisinin arms (three and two arms, respectively). Two trial arms used bulaquine. Seven PQ arms used low dose (six with artemisinin), 11 arms used moderate dose (seven with artemisinin), and the remaining arms used high dose. Fifteen trials tested for G6PD status: 11 excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and three included all, irrespective of status. The remaining 10 trials either did not test or did not report on testing.No cluster trials evaluating community effects on malaria transmission met the inclusion criteria.With artemisinin treatmentLow dose PQInfectiousness (participants infectious to mosquitoes) was reduced (day 3 or 4: RR 0.12, 95% CI 0.02 to 0.88, 3 trials, 105 participants; day 8: RR 0.34, 95% CI 0.07 to 1.58, 4 trials, 243 participants; low certainty evidence). This translates to a reduction in percentage of people infectious on day 3 or 4 from 14% to 2%, and, for day 8, from 4% to 1%; the waning infectiousness in the control group by day 8 making the absolute effect smaller by day 8. For gametocytes detected by PCR, there was little or no effect of PQ at day 3 or 4 (RR 1.02, 95% CI 0.87 to 1.21; 3 trials, 414 participants; moderate certainty evidence); with reduction at day 8 (RR 0.52, 95% CI 0.41 to 0.65; 4 trials, 532 participants; high certainty evidence). Severe haemolysis was infrequent, with or without PQ, in these groups with few G6PD-deficient individuals (RR 0.98, 95% CI 0.69 to 1.39; 4 trials, 752 participants, moderate certainty evidence).Moderate dose PQInfectiousness was reduced (day 3 or 4: RR 0.13, 95% CI 0.02 to 0.94; 3 trials, 109 participants; day 8 RR 0.33, 95% CI 0.07 to 1.57; 4 trials, 246 participants; low certainty evidence). Illustrative risk estimates for moderate dose were the same as low dose. The pattern and level of certainty of evidence with gametocytes detected by PCR was the same as low dose, and severe haemolysis was infrequent in both groups.High dose PQInfectiousness was reduced (day 4: RR 0.2, 95% CI 0.02 to 1.68, 1 trial, 101 participants; day 8: RR 0.18, 95% CI 0.02 to 1.41, 2 trials, 181 participants, low certainty evidence). The effects on gametocyte prevalence showed a similar pattern to moderate and low dose PQ. Trials did not systematically report evidence of haemolysis.With non-artemisinin treatmentTrials with non-artemisinin treatment have been conducted only for moderate and high dose PQ. With high dose, infectiousness appeared markedly reduced on day 5 (RR 0.09, 95% CI 0.01 to 0.62; 30 participants, very low certainty evidence), with similar reductions at day 8. For both moderate dose (two trials with 221 people) and high dose (two trials with 30 people), reduction in gametocytes (detected by microscopy) showed similar patterns as for artemisinin treatments, with little or no effect at day 4 or 5, and larger effects by day 8. No trials with non-artemisinin partner drugs systematically sought evidence of severe haemolysis.Two trials comparing bulaquine with PQ suggest bulaquine may have larger effects on gametocytes by microscopy on day 8 (RR 0.41, 95% CI 0.26 to 0.66; 2 trials, 112 participants).
AUTHORS' CONCLUSIONS
A single low dose of PQ (0.25 mg/kg) added to artemisinin-based combination therapy for malaria reduces infectiousness of people to mosquitoes at day 3-4 and day 8, and appears as effective as higher doses. The absolute effect is greater at day 3 or 4, and smaller at day 8, in part because of the lower infectiousness in the control group. There was no evidence of increased haemolysis at 0.25 mg/kg, but few G6PD-deficient individuals were included in the trials. The effect on infectiousness precedes the effect of PQ on gametocyte prevalence. We do not know whether single dose PQ could reduce malaria transmission at community level.
Topics: Adult; Antimalarials; Artemisinins; Child; Chloroquine; Drug Combinations; Glucosephosphate Dehydrogenase Deficiency; Humans; Malaria, Falciparum; Mefloquine; Non-Randomized Controlled Trials as Topic; Plasmodium falciparum; Primaquine; Pyrimethamine; Quinine; Randomized Controlled Trials as Topic; Sulfadoxine; Time Factors
PubMed: 29393511
DOI: 10.1002/14651858.CD008152.pub5 -
The Cochrane Database of Systematic... 2000Inhibition of prostaglandin synthesis mediates closure of the ductus arteriosus and renal side effects after indomethacin administration. Because furosemide increases... (Review)
Review
BACKGROUND
Inhibition of prostaglandin synthesis mediates closure of the ductus arteriosus and renal side effects after indomethacin administration. Because furosemide increases prostaglandin production, it could potentially help prevent indomethacin-related toxicity but also decrease ductal response to indomethacin.
OBJECTIVES
The primary objectives of this review were to assess (1) whether furosemide affects the incidence of failure of ductal closure after indomethacin and that of indomethacin-related toxicity and (2) the effect of furosemide on mid-term and long-term outcome. The secondary objective was to determine whether the effect of furosemide on renal function and water balance depends on prior extracellular volume (assessed by blood urea nitrogen [BUN]/creatinine ratio).
SEARCH STRATEGY
We searched electronic databases (Medline, Embase and Cochrane) and selected abstract books, without language restriction.
SELECTION CRITERIA
We selected studies with (1) random allocation to either indomethacin alone or indomethacin and furosemide and (2) analysis of either short-term risk-benefit ratio of furosemide, mid- or long-term outcome, or the relationship between extracellular volume at study entry and changes in renal function.
DATA COLLECTION AND ANALYSIS
We assessed studies for possible bias and for quality of assessment of ductal patency. We assessed categorical variables using relative risk and absolute risk reduction. We assessed the effects of furosemide on renal function and fluid balance by comparing changes from baseline in the treatment group with those in controls. Subsets were determined a priori based on BUN/creatinine ratio at study entry.
MAIN RESULTS
All 3 studies fulfilling the entry criteria had limitations, including possible or definite bias. There was substantial heterogeneity among studies. Furosemide administration did not significantly increase the risk of failure of ductal closure; however, sample size was insufficient to rule out even a 31% increase. In the subset with initial BUN/creatinine ratio > 20 mg/mg, 2 of 18 patients receiving furosemide could not complete a 3-dose course of indomethacin because of toxicity. Minimal or no information was available about any of the other main outcome variables. Furosemide increased urine output regardless of the initial BUN/creatinine ratio, leading to a 5% weight loss during a 3-dose course, an undesired effect in patients with initial BUN/creatinine ratio > 20 mg/mg. Furosemide increased creatinine clearance only in patients with initial BUN/creatinine ratio <20 mg/mg.
REVIEWER'S CONCLUSIONS
There is not enough evidence to support the administration of furosemide to premature infants treated with indomethacin for symptomatic patent ductus arteriosus. Furosemide appears to be contraindicated in the presence of dehydration in those infants.
Topics: Cyclooxygenase Inhibitors; Diuretics; Ductus Arteriosus, Patent; Furosemide; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Kidney
PubMed: 10796253
DOI: 10.1002/14651858.CD001148 -
The Cochrane Database of Systematic... Jan 2009Children with HIV are at increased risk of acquiring tuberculosis (TB), a common cause of acute and chronic respiratory disease and death in HIV-infected children living... (Review)
Review
BACKGROUND
Children with HIV are at increased risk of acquiring tuberculosis (TB), a common cause of acute and chronic respiratory disease and death in HIV-infected children living in areas where prevalence of the disease is high. Children infected with HIV and TB have worse outcomes than HIV-uninfected children who have TB; thus, preventing the infection and disease in HIV-infected children is potentially an important public health intervention. Isoniazid, an anti-tuberculosis medication, has been used effectively to prevent TB in HIV-uninfected children, but currently there are no guidelines on the use of TB preventive therapy in HIV-infected children.
OBJECTIVES
To determine the impact of TB preventive therapy on TB-related incidence and death in HIV-infected children
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register (CENTRAL/CCTR), Cochrane HIV/AIDS Group Specialized Register, MEDLINE/PubMed, EMBASE, and AIDSearch. In addition, we scanned reference lists, manually searched conference abstracts, and contacted content experts.
SELECTION CRITERIA
We included studies of HIV-infected children randomised to receive TB preventive therapy or placebo, or an alternative TB preventive regimen. Participants could have tuberculin skin test results that were positive or negative.
DATA COLLECTION AND ANALYSIS
Two authors independently used the study selection criteria, assessed methodological quality and extracted data. Effects were assessed using hazard ratios.
MAIN RESULTS
One trial met the selection criteria for the review. The trial participants were HIV-infected children, most of whom were not taking antiretroviral therapy. Subjects were randomised to isoniazid and cotrimoxazole or placebo and cotrimoxazole, given daily or three times a week. The trial showed a marked reduction in TB incidence and death in the isoniazid group. As yet, however, there are no long-term follow-up data on the durability of the protective effect or on possible long-term adverse events. This trial also was unable to assess the impact of isoniazid prophylaxis on children receiving antiretroviral therapy.
AUTHORS' CONCLUSIONS
Isoniazid prophylaxis in HIV-infected children has the potential to play a major public health role by reducing TB incidence and death. As yet, however, data are insufficient to guide the duration of prophylaxis and to support its use in children using highly active antiretroviral therapy (HAART) and in those living in areas of low TB prevalence. Further studies are needed to assess whether TB preventive therapy is of benefit in all HIV-infected children, irrespective of use of antiretroviral treatment, the optimal duration of preventive therapy, or long-term adverse events.
Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antitubercular Agents; Child; HIV Infections; Humans; Incidence; Isoniazid; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary
PubMed: 19160285
DOI: 10.1002/14651858.CD006418.pub2 -
The Cochrane Database of Systematic... Jan 2006The majority of children with HIV infection live in low-income countries without access to antiretroviral drugs. The prevention and early treatment of opportunistic... (Review)
Review
BACKGROUND
The majority of children with HIV infection live in low-income countries without access to antiretroviral drugs. The prevention and early treatment of opportunistic infections are the mainstay of their medical management. Cotrimoxazole is cheap and effective against a wide range of organisms, including Pneumocystis jiroveci pneumonia (PCP), which is an important cause of death and illness in the first year of life. It is safe with relatively few side effects. Diagnosis of HIV in children is complicated by the presence of maternal antibodies in early life. Providing prophylaxis based initially on maternal status is one possible solution. However, routine prophylactic treatment is difficult to deliver in low-resource settings, and could also lead to increased resistance to the drug.
OBJECTIVES
To assess the effects of routinely administered cotrimoxazole on death and illness episodes in children with HIV infection, and in infants of HIV-infected mothers.
SEARCH STRATEGY
We searched the Cochrane HIV/AIDS registry, MEDLINE, the Cochrane Controlled Trials Register, LILACS, AIDSLINE, AIDSTRIALS and AIDSDRUGS databases, and proceedings and abstracts from AIDS and TB conferences (search date Feb 2005). We checked reference lists of pertinent articles, and contacted pharmaceutical companies and experts in the field.
SELECTION CRITERIA
Randomised or quasi-randomised trials comparing routinely administered cotrimoxazole versus placebo or no treatment in children (age less than 15 years) with HIV infection, or children less than 18 months with HIV infected mothers.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial eligibility and quality. Where data were incomplete or unclear trial authors were contacted for further details.
MAIN RESULTS
One study was identified that fulfilled the inclusion criteria. It studied 534 children with HIV infection in Lusaka, Zambia. The study was conducted in an area of high bacterial resistance to cotrimoxazole (60-80%). A reduction in mortality of 33% was seen in the cotrimoxazole group as compared to placebo, relative risk 0.67 (95% CI 0.53 - 0.85). There was also a beneficial effect on hospitalisation, relative risk 0.77 (95% CI 0.62 - 0.96). There was no difference in adverse events between groups, and the beneficial effect was seen across all ages and CD4%.
AUTHORS' CONCLUSIONS
A single trial has shown a beneficial effect from the use of cotrimoxazole prophylaxis in HIV infected children in Zambia. It must be decided whether this can be extrapolated to other resource-poor settings.
Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Child; Humans; Infant; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 16437457
DOI: 10.1002/14651858.CD003508.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 -
Bulletin of the World Health... Feb 2012To determine whether cotrimoxazole reduces mortality in adults receiving antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in low- and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine whether cotrimoxazole reduces mortality in adults receiving antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in low- and middle-income countries through a systematic review and meta-analysis.
METHODS
PubMed and Embase were searched for randomized controlled trials and prospective and retrospective cohort studies that compared mortality or morbidity in HIV-infected individuals aged ≥ 13 years on cotrimoxazole and ART and on ART alone. The Newcastle-Ottawa Quality Assessment Scale was used to assess selection, confounding and measurement bias. Publication bias was assessed using Egger's and Begg's tests. Sensitivity analysis was performed because the I-squared statistic indicated substantial heterogeneity in study results. A random-effects model was used for meta-analysis.
FINDINGS
Nine studies were included. Begg and Egger P-values for the seven that reported the effect of cotrimoxazole on mortality were 0.29 and 0.49, respectively, suggesting no publication bias. The I-squared statistic was 93.2%, indicating high heterogeneity in study results. The sensitivity analysis showed that neither the follow-up duration nor the percentage of individuals with World Health Organization stage 3 or 4 HIV disease at baseline explained the heterogeneity. The summary estimate of the effect of cotrimoxazole on the incidence rate of death was 0.42 (95% confidence interval: 0.29-0.61). Since most studies followed participants for less than 1 year, it was not possible to determine whether cotrimoxazole can be stopped safely after ART-induced immune reconstitution.
CONCLUSION
Cotrimoxazole significantly increased survival in HIV-infected adults on ART. Further research is needed to determine the optimum duration of cotrimoxazole treatment in these patients.
Topics: Anti-HIV Agents; Anti-Infective Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; Confidence Intervals; Global Health; HIV Infections; Humans; Mortality; Odds Ratio; Statistics as Topic; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 22423164
DOI: 10.2471/BLT.11.093260