Antibiotic prescription in ambulatory care for COVID-19 patients: a cohort analysis in four European countries.

OBJECTIVE: To analyse antibiotic prescription rates in ambulatory care for COVID-19 patients by general practitioners (GPs) in four European countries. METHODS: A total of 4,513,955 anonymised electronic prescribing records of 3656 GPs in four European countries were analysed. Diagnosis and prescriptions were retrieved. Antibiotic prescription rates during COVID-19 consultations were analysed and compared between France, the UK, Belgium and Romania. RESULTS: Overall prescription rate was in France and Belgium (6.66 and 7.46%). However, analysing median GP prescribing rates, we found that 33.9% of the GPs in Belgium prescribed antibiotics with a median of 16 prescriptions per 100 COVID-19 consultations, while 55.21% of the GPs in France prescribed a median of 8 antibiotic prescriptions per 100 COVID-19 consultations. Overall antibiotic prescription rates were less in Romania than in the UK (22% vs 32%); however, 73% of the Romanian GPs vs 57% of the British GPs prescribed antibiotics. Depending on the country, the proportion of each type of antibiotic was statistically different, with the proportion of azithromycin being more than 50% of all antibiotics in each country except for the UK where it was less than 1%. CONCLUSION: Both individual GPs prescribing patterns in addition to overall consumption patterns should be analysed in order to implement a tailored antimicrobial stewardship programme. Furthermore, antibiotic prescribing rates in COVID-19 are lower than other respiratory tract infections.

Optimizing Betalactam Clinical Response by Using a Continuous Infusion: A Comprehensive Review.

INTRODUCTION: Antimicrobial resistance is a major healthcare issue responsible for a large number of deaths. Many reviews identified that PKPD data are in favor of the use of continuous infusion, and we wanted to review clinical data results in order to optimize our clinical practice. METHODOLOGY: We reviewed Medline for existing literature comparing continuous or extended infusion to intermittent infusion of betalactams. RESULTS: In clinical studies, continuous infusion is as good as intermittent infusion. In the subset group of critically ill patients or those with an infection due to an organism with high MIC, a continuous infusion was associated with better clinical response. CONCLUSIONS: Clinical data appear to confirm those of PK/PD to use a continuous infusion in severely ill patients or those infected by an organism with an elevated MIC, as it is associated with higher survival rates. In other cases, it may allow for a decrease in antibiotic daily dosage, thereby contributing to a decrease in overall costs.

Injectable long acting antiretroviral for HIV treatment and prevention: perspectives of potential users.

BACKGROUND: The use of long acting injectable (LAA) antiretroviral drugs may be an alternative option for HIV treatment and prevention. Our study focused on patient perspectives to understand which individuals, among people with HIV (PWH) and pre-exposure prophylaxis (PrEP) users, would constitute the preferential target for such treatments in terms of expectations, tolerability, adherence and quality of life. METHODS: The study consisted in one self-administrated questionnaire. Data collected included lifestyle issues, medical history, perceived benefits and inconveniences of LAA. Groups were compared using Wilcoxon rank tests or Fisher's exact test. RESULTS: In 2018, 100 PWH and 100 PrEP users were enrolled. Overall, 74% of PWH and 89% of PrEP users expressed interest for LAA with a significantly higher rate for PrEP users (p = 0.001). No characteristics were associated with acceptance of LAA in both groups in term of demographics, lifestyle or comorbidities. CONCLUSION: PWH and PrEP users expressed a high level of interest in LAA, since a large majority seems to be in favor of this new approach. Further studies should be conducted to better characterize targeted individuals.

Bacterial Epidemiology of Surgical Site Infections after Open Fractures of the Lower Limb: A Retrospective Cohort Study.

Open lower limb fractures are common injuries, and the occurrence of infectious complications after open fractures is a usual problem. The rate of surgical site infections (SSIs) and the nature and resistance of the germs responsible for SSIs remain poorly described. Our aim was to describe the bacterial epidemiology of SSIs after surgical management of an open lower limb fracture. We conducted a retrospective monocentric cohort study from 1 January 2012 to 31 December 2020 based on the analysis of inpatient records in a non-university hospital of Ile de France region. All patients who underwent surgery for an open lower limb fracture were included. A total of 149 patients were included. In our population, 19 (12.7%) patients developed an SSI. Of these 19 patients, the sample was polymicrobial in 9 (47.4%) patients. In 9 (45%) cases, the samples identified a group 3 enterobacteria, Enterobacter cloacae being the main one in 7 (36.9%) cases. Staphylococci were identified in 11 patients, with Staphylococcus aureus in 9 (47.4%). All Staphylococcus aureus were susceptible to methicillin, and all enterobacteria were susceptible to C3G. Among all SSI, 10 (58.8%) contained at least one germ resistant to amoxicillin/clavulanic acid (AMC). The SSIs rate was 12.7%. The main pathogens identified were Enterobacter cloacae and Staphylococcus aureus. The presence of early SSI caused by group 3 Enterobacteriaceae renders current antibiotic prophylaxis protocols inadequate with AMC in half the cases.

Trimethoprim-sulfamethoxazole as de-escalation in ventilator-associated pneumonia: a cohort study subanalysis.

PURPOSE: This is a subanalysis of a previous study which compared the effectiveness of trimetoprim-sulfametoxazole (TMP-SMX) with all other regimens for treatment of ventilator-associated pneumonia (VAP). Aim of the current study was to focus on the effectiveness of a strategy based on TMP-SMX as de-escalation from ß-lactam including regimens. METHODS: Retrospective cohort study including patients who were hospitalized for VAP from 2011 to 2019. Patients were distributed in two groups: NO SWITCH TO TMP-SMX group, including patients who received ß-lactams for all treatment duration, and SWITCH TO TMP-SMX group, which included patients who switched to TMP-SMX from a ß-lactam including regimen after microbiology diagnosis. Three clinical outcomes were analyzed: mortality at 30 days from the start of the antibiotic treatment (T30), mortality at the end of treatment (EoT), and acquisition of multidrug-resistant bacteria during hospitalization in intensive care unit. RESULTS: Overall, 70 patients were included in the current study, 32/70 (45.7%) in NO SWITCH TO TMP-SMX group and 38/70 (54.3%) in SWITCH TO TMP-SMX group, 37/70 (52.8%) had been already included in the previous study. No significant differences in clinical outcomes and patient's characteristics were found when the two groups were compared. CONCLUSIONS: De-escalation to TMP-SMX for VAP treatment was not associated with higher mortality at EoT and T30 than standard treatment with ß-lactam. Monotherapy with TMP-SMX as de-escalation from broad-spectrum empirical regimens is a ß-lactam sparing strategy worthy to be further investigated in either multicenter cohort studies or randomized clinical trials.

Perspectives of injectable long acting antiretroviral therapies for HIV treatment or prevention: understanding potential users' ambivalences.

Recent clinical trial data showed that injectable long-acting antiretroviral treatment (LA-ART) every four or eight weeks could become an alternative option for HIV treatment or prevention. The purpose of our study was to explore perceptions and potential users' points of views of this new mode of administration through individuals' therapeutic itinerary and their singular history with ART. Between 2018 and 2019, a qualitative study was conducted in two University Hospitals in Paris, France. In-depth interviews were conducted with 15 virologically controlled People Living with HIV (PLWH) and 13 men on pre-exposure prophylaxis (PrEP) for at least six months. Interviews, focused on the daily experience with ART, were recorded, transcribed, and analyzed using thematic content analysis. Collected discourses were organized around three emergent concerns: social, material and experimental. Each of these concerns was perceived as ambivalent, balanced by skepticism and hope. It revealed the complexity of each individual's relationship to their HIV treatment or PrEP, leading to balance the injectable LA-ART popularity reported within clinical trials. This new mode of administration may be a suitable alternative for some PLWH and PrEP users, a "simplification" compared to the oral route. It opens a window for "customizable" ART-treatment according to individuals' lives.

Trimetoprim-sulfametoxazole in ventilator-associated pneumonia: a cohort study.

To evaluate the effectiveness of trimetoprim-sulfametoxazole (TMP-SMX) for treatment of ventilator-associated pneumonia (VAP). A retrospective cohort study including patients with VAP from 2011 to 2017. Two groups were analysed: TMP-SMX group, including patients who had received TMP-SMX (as first-line and as de-escalation), and No-TMP-SMX group, including patients who had not received TMP-SMX treatment. Primary clinical outcome was mortality at 30 days from starting the antibiotic treatment (T30). Secondary outcomes were mortality at end of treatment (EoT), day survival at T30, and acquisition of multidrug-resistant bacteria during hospitalization in intensive care unit. Eighty cases of VAP were included and devised into two groups: No-TMP-SMX (31/80; 39%) and TMP-SMX (49/80; 61%). Univariate analysis showed no significant differences were found when the TMP-SMX group was compared with the No-TMP-SMX group, except for frequency of male gender (p = 0.025). No significant statistical correlations between mortality at T30 and individual factors were detected by the multivariate model. No cases of either severe allergy or Clostridium difficile disease were reported in the TMP-SMX and No-TMP-SMX groups. TMP-SMX treatment was not associated with higher mortality at EoT and T30 in comparison with the No-TMP-SMX group. TMP-SMX had a good safety profile, in terms of ecology (acquisition of MDR bacteria and Clostridium difficile disease) and clinical management (no allergy events).

Evolution of haemostatic parameters and risk of bleeding during treatment with cefazolin.

In 2017, five cases of severe haemorrhages during treatment with cefazolin occurred in France. The aim of this study was to assess the risk of haemorrhage related to treatment with cefazolin by evaluating haemostatic parameters and bleeding events. A retrospective study was conducted from January 2016 to December 2017. Two populations were analysed: (i) overall population, which included all patients treated with cefazolin during this period and (ii) coagulation study population, which included all patients treated with cefazolin with available coagulation parameters (activated partial thromboplastin time (aPTT) and international normalised ratio (INR) at baseline and at the end of treatment or EoT). Values of either aPTT or INR at baseline and at EoT were compared. Cases of severe haemorrhages were reported and correlated with values of aPTT and INR. Overall, 132 patients received cefazolin and 59/132 (45%) were included in the coagulation study group. A significant increase of median aPTT was observed from baseline to EoT (39.5 and 44.3 sec; p = 0.004, respectively). Overall, severe haemorrhage occurred in 7/132 (5%) patients. Coagulation parameters were available in three of them, and no correlation was observed between bleeding events and aPTT increase. This study showed that bleeding is probably more frequent than ever reported before during cefazolin treatment. The significant increase of aPTT observed during cefazolin treatment was not correlated with risk of haemorrhage. Further studies are needed to explore the possible physio-pathological pathways behind the modification of haemostatic parameters and risk of haemorrhage.

Detection of Fusobacterium nucleatum in culture-negative brain abscess by broad-spectrum bacterial 16S rRNA Gene PCR.

BACKGROUND: Fusobacterium nucleatum is a strict anaerobic microorganism commensal to the human oropharynx and gastrointestinal tract, which causes a wide spectrum of human diseases and it is an important pathogen in abscesses. CASE PRESENTATION: We report the case of a previously healthy 64-year-old woman with multiple abscesses due to Fusobacterium nucleatum, involving liver, pleura and brain. Fusobacterium was not recovered from blood cultures nor from culture of hepatic, pleural and brain drain fluid. The diagnosis was obtained by polymerase chain reaction amplification of bacterial deoxyribonucleic acid in brain abscess drain. CONCLUSIONS: Fusobacterium spp., should be considered in patients with any organ abscess, especially in case of invasive disease with multiple secondary site involving brain. MOLECULAR: techniques might be of special usefulness in cases that remain negative in culture to obtain the diagnosis and perform adequate treatment.

Efficacy of hepatitis B sero-vaccination in newborns of African HBsAg positive mothers.

BACKGROUND: Maternal-infant transmission of hepatitis B virus (HBV) during birth carries a high risk of chronic HBV infection in infants. Appropriate neonatal prophylaxis is effective in preventing perinatal transmission of HBV. The purpose of this study was to evaluate the protective efficacy of anti-HBV sero-vaccination in newborns of HBsAg positive mothers from Mayotte, French island in the Mozambican canal. PATIENTS AND METHODS: One-hundred newborns of HBsAg positive mothers were identified retrospectively on the basis of hospital medical record and hepatitis B immune globulin (HBIG) prescriptions review from 1994 to 2007. To determine the rate of protective efficacy of neonatal prophylaxis defined by anti HBs antibodies >10 IU/mL with negative HBsAg, anti HBc and HBV DNA testing, HBV serological markers were performed in vaccinated children. RESULTS: Eighty-three of 100 newborns (83%) were given a complete sero-vaccination. Maternal HBe Ag status at delivery (available in 93%) was positive in 56 (60%) of cases and HBV viral load (available in 57%) was <5 logIU/mL, between 5 and 7 logsIU/mL and >7 logsIU/mL in 23 (40.4%), 12 (21%) and 22 (38.6%), respectively. HBV markers in all children at a median age of 5 years [IQR 2-8] showed that 76% were protected with anti HBs >10 IU/mL, despite incomplete sero-vaccination in 12 infants; 6% of infants had anti-HBs and anti-HBc positivity with undetectable HBV DNA, 1% had isolated anti HBc while 14% were seronegative. Only 3% had evidence of immunoprophylaxis failure: 1 infant was HBsAg carrier and 2 had detectable HBV DNA without HBsAg (occult HBV infection). The only factor associated with sustained protective efficacy was on time serological control performed within one year of life, whereas maternal age, HBeAg status and HBV viral load on delivery were not. CONCLUSION: The anti-HBV sero-vaccination of newborns of HBsAg-positive mothers is fairly done in Mayotte and allows a high protection of mother-to-child transmission in a mean endemic area with fair safety. Screening of sero-vaccination failures has to be reinforced in order either to revaccinate or to treat infected children.

Brief communication: case reports of ribavirin treatment for chronic hepatitis E.

BACKGROUND: There is currently no accepted treatment of chronic hepatitis E virus (HEV) infection. OBJECTIVE: To report 2 patients in whom ribavirin therapy seemed to alter the natural history of chronic HEV infection. DESIGN: Case reports. SETTING: Hepatology unit of a tertiary care center in France. PATIENTS: A kidney and pancreas transplant recipient and a patient with idiopathic CD4(+) T lymphocytopenia, both with biopsy-proven chronic HEV infection. INTERVENTION: Patients received oral ribavirin, 12 mg/kg of body weight daily for 12 weeks. MEASUREMENTS: Liver function tests, detection of HEV RNA (viremia and stool shedding) by reverse transcriptase polymerase chain reaction, and anti-HEV IgM and IgG antibodies. RESULTS: Both patients had normalized liver function test results after 2 weeks of treatment and cleared HEV after 4 weeks of treatment. Hepatitis E virus RNA remained undetectable in the serum and stools throughout follow-up (3 months and 2 months for the first and second patient, respectively). Side effects were considered mild. LIMITATION: Given the relatively short follow-up, the achievement of HEV eradication could not be claimed. CONCLUSION: Ribavirin is a potentially effective treatment of HEV infection and should be evaluated in patients with chronic HEV infection. PRIMARY FUNDING SOURCE: None.

Serologic response to hepatitis B vaccination in HIV-Infected patients with isolated positivity for antibodies to hepatitis B core antigen.

We assessed the safety and immunogenicity of hepatitis B vaccination among 40 human immunodeficiency virus-infected patients with isolated positivity for antibodies to hepatitis B core antigen. No baseline factors were found to be predictive of an anamnestic response, which occurred in 32.5% of the patients. The overall response rate among patients without an anamnestic response was 74.0% after 3-6 vaccine doses.