Efficacy and safety of hydroxychloroquine for treatment of mild SARS-CoV-2 infection and prevention of COVID-19 severity in pregnant and postpartum women: A randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Pregnant women have an increased risk of severe COVID-19. Evaluation of drugs with a safety reproductive toxicity profile is a priority. At the beginning of the pandemic, hydroxychloroquine (HCQ) was recommended for COVID-19 treatment. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted in eight teaching hospitals in Spain to evaluate the safety and efficacy of HCQ in reducing viral shedding and preventing COVID-19 progression. Pregnant and postpartum women with a positive SARS-CoV-2 PCR (with or without mild COVID-19 signs/symptoms) and a normal electrocardiogram were randomized to receive either HCQ orally (400 mg/day for 3 days and 200 mg/day for 11 days) or placebo. PCR and electrocardiogram were repeated at day 21 after treatment start. Enrollment was stopped before reaching the target sample due to low recruitment rate. Trial registration EudraCT #: 2020-001587-29, on April 2, 2020. CLINICAL TRIALS: gov # NCT04410562, registered on June 1, 2020. RESULTS: A total of 116 women (75 pregnant and 41 post-partum) were enrolled from May 2020 to June 2021. The proportion of women with a positive SARS-CoV-2 PCR at day 21 was lower in the HCQ group (21.8%, 12/55) than in the placebo group (31.6%, 18/57), although the difference was not statistically significant (P = 0.499). No differences were observed in COVID-19 progression, adverse events, median change in QTc, hospital admissions, preeclampsia or poor pregnancy and perinatal outcomes between groups. CONCLUSIONS: HCQ was found to be safe in pregnant and postpartum women with asymptomatic or mild SARS-CoV-2 infection. Although the prevalence of infection was decreased in the HCQ group, the statistical power was insufficient to confirm the potential beneficial effect of HCQ for COVID-19 treatment.

[Excess mortality in nursing homes during the first wave of the Covid-19 pandemic]. / Surmortalité dans les Ehpad pendant la première vague de la pandémie de la Covid-19.

Overall mortality in France is 147 568 deaths since the first wave. Although accounting for nearly 20% of deaths in France, the excess mortality in long-term care facilities compared to previous years has not been fully studied. The Covid-19 pandemic has highlighted the vulnerability of residents in long-term care facilities, with highly dependent elderly patients being the most exposed to the risk of death, with deleterious effects linked to the effects of confinement, which in Ehpad has resulted in major isolation of residents and the appearance by care teams of cognitive disorders appearing or deteriorating in residents, as well as a significant loss of autonomy.

Arthritis Caused by Nannizziopsis obscura, France.

Nannizziopsis spp., fungi responsible for emerging diseases, are rarely involved in human bone and joint infections. We present a rare case of septic arthritis with necrotizing cellulitis caused by N. obscura in a patient in France who had undergone kidney transplant. Rapid, aggressive medical and surgical management led to a favorable outcome.

Burden of malaria in pregnancy among adolescent girls compared to adult women in 5 sub-Saharan African countries: A secondary individual participant data meta-analysis of 2 clinical trials.

BACKGROUND: Malaria is among the top causes of death in adolescent girls (10 to 19 years) globally. Adolescent motherhood is associated with increased risk of adverse maternal and neonatal outcomes. The interaction of malaria, adolescence, and pregnancy is especially relevant in malaria endemic areas, where rates of adolescent pregnancy are high. However, data on burden of malaria among adolescent girls are limited. This study aimed at investigating whether adolescent girls were at a greater risk of experiencing malaria-related outcomes in pregnancy-parasitaemia and clinical disease-than adult women. METHODS AND FINDINGS: An individual secondary participant-level meta-analysis was conducted using data from 5,804 pregnant women participating in 2 malaria prevention clinical trials in Benin, Gabon, Kenya, Mozambique, and Tanzania between 2009 and 2014. Of the sample, 1,201 participants were adolescent girls with a mean age of 17.5 years (standard deviation (SD) 1.3) and 886 (73.8%) of them primigravidae. Among the 4,603 adult women with mean age of 27.0 years (SD 5.4), 595 (12.9%) were primigravidae. Mean gestational age at enrolment was 20.2 weeks (SD 5.2) and 1,069 (18.4%) participants were HIV-infected. Women were followed monthly until the postpartum visit (1 month to 6 weeks after delivery). This study considered outcomes including clinical episodes during pregnancy, peripheral parasitaemia at delivery, and placental malaria. A 2-stage meta-analysis approach was followed by pooling single multivariable regression results into standard DerSimonian-Laird random-effects models. Adolescent girls were more likely than adult women to present with clinical malaria during pregnancy (incidence risk ratio (IRR) 1.70, 95% confidence interval (CI) 1.20; 2.39, p-value = 0.003, I2 = 0.0%, N = 4,092), peripheral parasitaemia at delivery (odds ratio (OR) 2.28, 95% CI 1.46; 3.55, p-value < 0.001, I2 = 0.0%, N = 3,977), and placental infection (OR 1.97, 95% CI 1.31; 2.98, p-value = 0.001, I2 = 1.4%, N = 4,797). Similar associations were observed among the subgroup of HIV-uninfected participants: IRR 1.72 (95% CI 1.22; 2.45, p-value = 0.002, I2 = 0.0%, N = 3,531) for clinical malaria episodes, OR 2.39 (95% CI 1.49; 3.86, p-value < 0.001, I2 = 0.0%, N = 3,053) for peripheral parasitaemia, and OR 1.88 (95% CI 1.06 to 3.33, p-value = 0.03, I2 = 34.9%, N = 3,847) for placental malaria. Among HIV-infected subgroups statistically significant associations were not observed. Similar associations were found in the subgroup analysis by gravidity. The small sample size and outcome prevalence in specific countries limited the inclusion of some countries in the meta-analysis. Furthermore, peripheral parasitaemia and placental malaria presented a considerable level of missing data-12.6% and 18.2% of participants had missing data on those outcomes, respectively. Given the original scope of the clinical trials, asymptomatic malaria infection was only assessed at the end of pregnancy through peripheral and placental parasitaemia. CONCLUSIONS: In this study, we observed that adolescent girls in sub-Saharan Africa (SSA) are more prone to experience clinical malaria episodes during pregnancy and have peripheral malaria and placental infection at delivery than adult women. Moreover, to the best of our knowledge, for the first time this study disaggregates figures and stratifies analyses by HIV infection. Similar associations were found for both HIV-infected and uninfected women, although those for HIV-infected participants were not statistically significant. Our finding suggests that adolescent girls may benefit from targeted malaria prevention strategies even before they become pregnant.

Discontinuing ß-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial.

BACKGROUND: Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of ß-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment. METHODS: We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Adult patients (aged ≥18 years) admitted to hospital with moderately severe community-acquired pneumonia (defined as patients admitted to a non-critical care unit) and who met prespecified clinical stability criteria after 3 days of treatment with ß-lactam therapy were randomly assigned (1:1) to receive ß-lactam therapy (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or matched placebo for 5 extra days. Randomisation was done using a web-based system with permuted blocks with random sizes and stratified by randomisation site and Pneumonia Severity Index score. Participants, clinicians, and study staff were masked to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. A non-inferiority margin of 10 percentage points was chosen. The primary outcome was assessed in all patients who were randomly assigned and received any treatment (intention-to-treat [ITT] population) and in all patients who received their assigned treatment (per-protocol population). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT01963442, and is now complete. FINDINGS: Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility, and after 3 days of ß-lactam treatment, 310 eligible patients were randomly assigned to receive either placebo (n=157) or ß-lactam treatment (n=153). Seven patients withdrew consent before taking any study drug, five in the placebo group and two in the ß-lactam group. In the ITT population, median age was 73·0 years (IQR 57·0-84·0) and 123 (41%) of 303 participants were female. In the ITT analysis, cure at day 15 occurred in 117 (77%) of 152 participants in the placebo group and 102 (68%) of 151 participants in the ß-lactam group (between-group difference of 9·42%, 95% CI -0·38 to 20·04), indicating non-inferiority. In the per-protocol analysis, 113 (78%) of 145 participants in the placebo treatment group and 100 (68%) of 146 participants in the ß-lactam treatment group were cured at day 15 (difference of 9·44% [95% CI -0·15 to 20·34]), indicating non-inferiority. Incidence of adverse events was similar between the treatment groups (22 [14%] of 152 in the placebo group and 29 [19%] of 151 in the ß-lactam group). The most common adverse events were digestive disorders, reported in 17 (11%) of 152 patients in the placebo group and 28 (19%) of 151 patients in the ß-lactam group. By day 30, three (2%) patients had died in the placebo group (one due to bacteraemia due to Staphylococcus aureus, one due to cardiogenic shock after acute pulmonary oedema, and one due to heart failure associated with acute renal failure) and two (1%) in the ß-lactam group (due to pneumonia recurrence and possible acute pulmonary oedema). INTERPRETATION: Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing ß-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption. FUNDING: French Ministry of Health.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

BACKGROUND: Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with ongoing transmission (WHO 2020). The World Health Organization (WHO) estimated that, in 2019, approximately 229 million cases of malaria occurred worldwide, with 94% occurring in the WHO's African region (WHO 2020). Of these malaria cases, an estimated 409,000 deaths occurred globally, with 67% occurring in children under five years of age (WHO 2020). Malaria also negatively impacts the health of women during pregnancy, childbirth, and the postnatal period (WHO 2020). Sulfadoxine/pyrimethamine (SP), an antifolate antimalarial, has been widely used across sub-Saharan Africa as the first-line treatment for uncomplicated malaria sTo examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure?Criteria for considering studies for this review Types of studies Inclusion criteria Randomized controlled trials (RCTs) Quasi-RCTs with randomization at the individual or cluster level conducted in malaria-endemic areas (areas with ongoing, local malaria transmission, including areas approaching elimination, as listed in the World Malaria Report 2020) (WHO 2020) Exclusion criteria Ecological studies Observational studies In vivo/in vitro studies Economic studies Systematic literature reviews and meta-analyses (relevant systematic literature reviews and meta-analyses will be excluded but flagged for grey literature screening) Types of participants Inclusion criteria Individuals of any age or gender, living in a malaria endemic area, who are taking antifolate antimalarial medications (inclu

Bloodstream infections in older population: epidemiology, outcome, and impact of multidrug resistance.

Bloodstream infections (BSIs) among older patients are frequent with high rate of mortality. Infections with multidrug-resistant organisms (MDRO) are associated with higher mortality than with susceptible microorganisms. We aimed to evaluate the prevalence of MDRO infection during BSI in older population and the factors associated with unfavorable outcome. This study is a retrospective cohort of all BSI episodes occurring among older patients (> 65yo), from April 1, 2010, to December 31, 2016, in a French university hospital for geriatric medicine. A total of 255 BSI episodes were analyzed. Mean age was 86.3±6.5 years, and sex ratio (M/F) was 0.96. Main comorbidities were orthopedic device (26.7%), active neoplasia (24.3%), and diabetes mellitus (18.4%). Main primary sites of infection were urinary tract infections (56.9%), respiratory tract infections (10.6%), intra-abdominal infections (7.1%), and skin and soft tissue infections (4.7%). Main bacteria identified were Escherichia coli (45.1%), Staphylococcus aureus (14.1%), enterococci (10.7%), coagulase-negative staphylococci (CoNS) (5.5%), and streptococci (5.1%). MDROs were involved in 17.2% of BSI (gram-negative bacilli: 9.0%; CoNS: 4.3%; and methicillin-resistant S. aureus (MRSA): 3.9%). The main factor associated with MDRO BSI was colonization with MDRO (OR=6.29; 95%CI=2.9-14.32). Total mortality was 18.4% and significantly higher in case of initial severity (OR=3.83; 95%CI=1.75-8.38), healthcare-associated infection (OR=5.29; 95%CI=1.11-25.30), and MRSA BSI (OR=9.16; 95%CI=1.67-50.16). BSI due to MDRO is frequent in older population and is strongly associated with carriage of MDRO. Healthcare-associated BSI, severe episodes, and BSI due to MRSA are associated with unfavorable outcome. In these cases, a broad-spectrum antibiotic should be promptly initiated.

Weekly Sequential Antibioprophylaxis for Recurrent Urinary Tract Infections Among Patients With Neurogenic Bladder: A Randomized Controlled Trial.

BACKGROUND: Recurrent urinary tract infections (R-UTIs) are the main cause of morbidity and hospitalizations in subjects with neurogenic bladder (NB) due to spinal cord injury (SCI). We evaluated the efficacy of weekly oral cyclic antibiotic (WOCA) prophylaxis (ie, the alternate weekly administration of 2 antibiotics) in preventing R-UTIs. METHODS: Randomized (1:1), open-label, superiority-controlled trial compared WOCA prophylaxis to no prophylaxis (control) for 6 months in patients with NB due to SCI, using clean intermittent self-catheterization, and suffering from R-UTIs. Primary outcome was incidence of symptomatic antibiotic-treated UTIs. Secondary outcomes were number of febrile UTIs, number of hospitalizations, WOCA tolerance, antibiotic consumption, number of negative urine cultures, and emergence of bacterial resistance in urinary, intestinal, and nasal microbiota. RESULTS: Forty-five patients were either allocated to the WOCA group (n = 23) or the control group (n = 22). Median (IQR) incidence of symptomatic antibiotic-treated UTIs was 1.0 (0.5-2.5) in the WOCA group versus 2.5 (1.2-4.0) (P = .0241) in the control group. No febrile UTIs were recorded in the WOCA group versus 9 (45.0%) (P < .001) in the control group. The median number of additional antibiotic treatment was 0.0 (IQR, 0.0-2.0) versus 3.0 (2.0-5.0) (P = .004) in the WOCA and control groups, respectively. Only few adverse events were reported. No impact on emergence of bacterial resistance was observed. CONCLUSIONS: WOCA is efficient and well tolerated in preventing R-UTIs in SCI patients. In our study, we did not observe any emergence of antibiotic resistance in digestive and nasal microbiological cultures. CLINICAL TRIALS REGISTRATION: NCT01388413.

Actinomycetoma Caused by Actinomadura mexicana, A Neglected Entity in the Caribbean.

Mycetoma is a chronic infection that is slow to develop and heal. It can be caused by fungi (eumycetoma) or bacteria (actinomycetoma). We describe a case of actinomycetoma caused by Actinomadura mexicana in the Caribbean region.

Systematic review of artemisinin embryotoxicity in animals: Implications for malaria control in human pregnancy.

Pregnant women are one of the most susceptible and vulnerable groups to malaria, the most important parasitic disease worldwide. Artemisinin-based combination therapies (ACTs) are recommended for the treatment of uncomplicated malaria in all population groups including pregnant women. However, due to the embryotoxicity observed in animal studies, ACTs have long been contraindicated during the first trimester in pregnant women. Despite the safety concerns raised in pre-clinical studies, recent findings on ACTs's use in pregnant women appear to be reassuring regarding safety and have prompted a revision of malaria treatment guidelines for first trimester of pregnancy. To contribute to the risk-benefit assessment of ACTs, we conducted a systematic literature review of animal studies published between 2007 and 2019, which evaluated the embryotoxic effects of artemisinin and its derivatives among pregnant mammals. Eighteen experimental studies fitted the inclusion criteria. These studies confirmed and further characterized the severe embryolethal and embryotoxic dose-dependent effects of artemisinin and its derivatives when administered during the organogenesis period in rats, rabbits and monkeys. Timing of administration and dosage of the drug were found to be key factors in the appearance of embryo damage. Overall, the translation of the findings of artemisinin derivatives use in animal studies to pregnant women remains disturbing. Thus, a policy change in the use of ACTs during the first trimester in pregnant women for the treatment of uncomplicated malaria does not seem pertinent and if implemented, it should be accompanied by solid pharmacovigilance systems, which are challenging to establish in malaria endemic countries.

Predictive factors for positive disco-vertebral biopsy culture in pyogenic vertebral osteomyelitis, and impact of fluoroscopic versus scanographic guidance.

BACKGROUND: The aims of this study were to identify the predictive factors for microbiological diagnosis through disco-vertebral biopsy (DVB) in patients with pyogenic vertebral osteomyelitis (PVO) and negative blood cultures, and compare the performance of DVB under fluoroscopic versus scanographic guidance. METHODS: We performed a cohort study comparing positive and negative DVB among patients with PVO. All cases of PVO undergoing a DVB for microbiological diagnosis in our center were retrospectively reviewed. Infections due to Mycobacterium tuberculosis, infections on foreign device, and non-septic diseases were excluded. Anamnestic, clinical, biological, microbiological, as well as radiological data were collected from medical charts thanks to a standardized data set. RESULTS: A total of 111 patients were screened; 88 patients were included. Microbiological cultures were positive in 53/88 (60.2%) patients. A thickening of the paravertebral tissue ≥10 mm on magnetic resonance imaging (MRI) in axial MR scans was a predictive factor of DVB microbiological positivity (52.4% vs. 13.3%; p = 0.006; OR = 5.4). Overall, 51 DVB were performed under fluoroscopic guidance and 37 under scanographic guidance. Considering lumbar DVB, 25/36 (69.4%) of cases yielded positive results under fluoroscopic guidance versus 5/15 (33.3%) under scanographic guidance (p = 0.02; OR = 4.4). No adverse event linked to DVB was notified. CONCLUSION: Every patient with PVO and negative blood cultures should undergo a DVB. A thickening of the paravertebral tissue ≥10 mm on MRI is associated with a higher rate of positive DVB culture. A lumbar DVB under fluoroscopic guidance is more sensitive than under scanographic guidance to identify the micro-organism involved.

Monomicrobial bone and joint infection due to Corynebacterium striatum: literature review and amoxicillin-rifampin combination as treatment perspective.

Corynebacterium striatum is a ubiquitous colonizer of human skin and mucous membranes. It is increasingly involved in infections, especially with prosthetic devices or in immunocompromised individuals. Microbiological diagnosis is challenging and bacterial resistance is a major concern. We performed a retrospective study of monomicrobial bone and joint infections (BJI) due to C. striatum in two referral centers from April 2012 to July 2017. We collected the patients' clinical and microbiological characteristics and outcomes. We also performed a literature review of BJI due to C. striatum. We identified 12 cases (nine prosthetic joint infections, one osteosynthetic device infection, one non-union, and one arthritis) in 11 patients, five of which were immunocompromised. Microbiological diagnosis was performed with prolonged culture media. Ten out of 12 strains were susceptible to aminopenicillin, a drug class not recommended for testing by the EUCAST/CASFM guidelines, and 8/12 patients were treated with amoxicillin-rifampicin. The cure rate was 8/12, after a median follow-up period of 487.5 days (IQR 140.3-1348.5). Twelve cases of BJI due to C. striatum were previously reported. Among them, 5/12 patients were immunocompromised, 3/12 cases were acute BJI, and 2/12 were device-related infections. The diagnosis was performed by PCR in one case, and 10/12 patients were treated with glycolipopeptides, with a cure rate of 11/12. We report the largest cohort of monomicrobial BJI with C. striatum. Determination of aminopenicillin susceptibility is essential since it is frequently active in our experience, even in BJI. The cure rate of this infection seems high.

Mefloquine for preventing malaria in pregnant women.

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; I2 statistic = 0%; moderate-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; moderate-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; moderate-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.

Mefloquine for preventing malaria in pregnant women.

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; I2 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.

Case of femoral pseudarthrosis due to Scedosporium apiospermum in an immunocompetent patient with successful conservative treatment and review of literature.

Scedosporium apiospermum is a ubiquitous filamentous fungus, commonly found in soil, sewage and polluted waters. It is rarely pathogenic but can cause a broad spectrum of clinical diseases, which can be localised or disseminate to distant organs. The disseminated form of the disease is mostly seen among immunocompromised patients. However, some rare cases of disseminated disease have been reported in immunocompetent individuals. Treatment of these infections is challenging because of their natural resistance to many antifungal agents. Here, we report the case of a 57-year-old immunocompetent patient diagnosed with femoral pseudarthrosis due to S. apiospermum, despite having no obvious clinical sign of infection. Previously, the patient had undergone four iterative femoral surgeries following a road traffic accident which occurred 20 years before. During its last surgery for pseudarthrosis, no clinical or biological signs of infection were present. Per operative samples tested positive for S. apiospermum. The patient was successfully treated with oral voriconazole during 6 months with an excellent tolerance. We also provide a review of literature on bone and joint infections due to Scedosporium spp. (S. apiospermum, Scedosporium boydii and Scedosporium aurantiacum), discussing the evolution of their management and outcome which seems to improve since the use of voriconazole.

Association between HIV infection and socio-economic status: evidence from a semirural area of southern Mozambique.

OBJECTIVES: To analyse the association between socio-economic status (SES) and HIV in Manhiça, a district of Southern Mozambique with one of the highest HIV prevalences in the world. METHODS: Data were gathered from two cross-sectional surveys performed in 2010 and 2012 among 1511 adults and from the household census of the district's population. Fractional polynomial logit models were used to analyse the association between HIV and SES, controlling for age and sex and taking into account the nonlinearity of covariates. The inequality of the distribution of HIV infection with regard to SES was computed through a concentration index. RESULTS: Fourth and fifth wealth quintiles, the least poor, were associated with a reduced probability of HIV infection compared to the first quintile (OR = 0.595, P-value = 0.009 and OR = 0.474, P-value < 0.001, respectively). Probability of HIV infection peaked at 36 years and then fell, and was always higher for women regardless of age and SES. HIV infection was unequally distributed across the SES strata. CONCLUSIONS: Despite the high HIV prevalence across the entire population of Manhiça, the poorest are at greatest risk of being HIV infected. While women have a higher probability of being HIV positive than men, both sexes showed the same infection reduction at higher levels of SES. HIV interventions in the area should particularly focus on the poorest and on women without neglecting anyone else, as the HIV risk is high for everyone.

Should we, and how to, optimize cefiderocol administration during severe nosocomial pneumonia due to carbapenem-resistant Acinetobacter baumanii? A viewpoint.

INTRODUCTION: Acinetobacter baumannii is classified by the Center for Disease Control and Prevention (CDC) as an "urgent threat" due to its ability to acquire and develop resistance to multiple classes of antibiotics. As a result, it is one of the most concerning pathogens in healthcare settings, with increasing incidence of infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) associated with high morbidity and mortality rates. Therefore, there are ongoing efforts to find novel treatment options, one of which is cefiderocol. We aim to review available evidence on cefiderocol use for severe nosocomial pneumonia due to carbapenem-resistant Acinetobacter baumannii METHODS: A comprehensive review was conducted from 2017 to 2023, covering articles from databases such as Pubmed, Scopus, and Embase, along with conference proceedings from ECCMID 2023. The primary focus was on severe nosocomial pneumonia due A. baumannii and cefiderocol. DISCUSSION: Cefiderocol, targeting periplasmic space Penicillin-Binding Proteins (PBPs) via siderophore transport pathways, exhibits promise against multi-drug resistant Gram-negative bacilli. Its effectiveness in treating CRAB pneumonia remains debated. The CREDIBLE trial reported higher mortality with cefiderocol compared to the best available treatment, while other cohort studies showed contrasting outcomes. Patient variations and pharmacokinetic factors may underlie these discrepancies. The recommended cefiderocol dosage regimen may fall short of desired pharmacokinetic targets, especially in critically ill patients and lung infections. Pulmonary factors hindering cefiderocol's entry into bacteria through iron transporters are overlooked in clinical breakpoints. Optimized dosing or combination regimens may enhance infection site exposure and outcomes. CONCLUSION: Further research is needed to determine the optimal cefiderocol dosage and administration (mono vs. dual therapy, continuous vs. intermittent infusion), in severe Acinetobacter baumannii nosocomial pneumonia.

Real-life impact on antimicrobial prescription of Syndromic Molecular Testing in adults hospitalized in infectious disease departments. Respiratory Syndromic Molecular Testing panel: Is it worth it?

BACKGROUND: While sensitive molecular diagnostic tests enable accurate and rapid diagnosis of many respiratory viruses, their impact on antibiotic management remains uncertain. Our study aimed to evaluate the impact of respiratory syndromic molecular testing panel in real-life clinical practice. METHOD: Retrospective descriptive study involving consecutive hospitalized patients in an infectious disease department who had been prescribed a respiratory syndromic molecular testing panel on nasopharyngeal swab samples (FilmArray Respiratory Panel 2 plus) during hospitalization from October 1st, 2021, to February 28th, 2023. RESULTS: All in all, 94 out of 210 screened patients were included in the study. Syndromic molecular testing results influenced antibiotic treatment in seven cases: discontinuation in four cases (three virus identifications), changes in two (Mycoplasma pneumoniae positive cases), and initiation in two (negative viral PCRs and one positive bacterial culture). CONCLUSION: In our study, respiratory syndromic molecular testing had low impact on antibiotic modification.

Exclusive oral antibiotic treatment for hospitalized community-acquired pneumonia: a post-hoc analysis of a randomized clinical trial.

OBJECTIVES: In this study, we aimed to assess the efficacy of different ways of administration and types of beta-lactams for hospitalized community-acquired pneumonia (CAP). METHODS: In this post-hoc analysis of randomized controlled trials (RCT) on patients hospitalized for CAP (pneumonia short treatment trial) comparing 3-day vs. 8-day durations of beta-lactams, which concluded to non-inferiority, we included patients who received either amoxicillin-clavulanate (AMC) or third-generation cephalosporin (3GC) regimens, and exclusively either intravenous or oral treatment for the first 3 days (followed by either 5 days of oral placebo or AMC according to randomization). The choice of route and molecule was left to the physician in charge. The main outcome was a failure at 15 days after the first antibiotic intake, defined as temperature >37.9°C, and/or absence of resolution/improvement of respiratory symptoms, and/or additional antibiotic treatment for any cause. The primary outcome according to the route of administration was evaluated through logistic regression. Inverse probability treatment weighting with a propensity score model was used to adjust for non-randomization of treatment routes and potential confounders. The difference in failure rates was also evaluated among several sub-populations (AMC vs. 3GC treatments, intravenous vs. oral AMC, patients with multi-lobar infection, patients aged ≥65 years old, and patients with CURB65 scores of 3-4). RESULTS: We included 200 patients from the original trial, with 93/200 (46.5%) patients only treated with intravenous treatment and 107/200 (53.5%) patients only treated with oral therapy. The failure rate at Day 15 was not significantly different among patients treated with initial intravenous vs. oral treatment [25/93 (26.9%) vs. 28/107 (26.2%), adjusted odds ratios (aOR) 0.973 (95% CI 0.519-1.823), p 0.932)]. Failure rates at Day 15 were not significantly different among the subgroup populations. DISCUSSION: Among hospitalized patients with CAP, there was no significant difference in efficacy between initial intravenous and exclusive oral treatment. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT01963442.