Effectiveness of temocillin in treatment of non-urinary tract infections caused by ESBL-producing Enterobacterales and risk factors for failure.

Objectives: To describe the real-life use of temocillin for non-urinary tract infections, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure. Method: Retrospective multicentric study in 14 tertiary care hospitals, including all patients who received at least one dose of temocillin for ESBL infections from 1 January 2016 to 31 December 2021 for non-urinary tract infections. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. Logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure. Results: Data on 163 infection episodes were collected; 133 were due to ESBL-producing Enterobacterales and 128 were included in the effectiveness analysis. Median (IQR) age was 61 (53-70) years and 61.7% of patients were male. Main indications were lower respiratory tract infection (LRTI; 28.9%), intra-abdominal infections (IAI; 28.1%) and cutaneous infections (12.5%). The main bacteria involved were Klebsiella pneumoniae (48.4%), Escherichia coli (25.0%) and Enterobacter cloacae (24.2%). Polymicrobial infections occurred in 45.3% of cases. Temocillin was used as monotherapy in 86/128 (67.2%). Failure was found in 36/128 (28.1%) cases. In multivariable analysis, the only factor associated with failure was initial severity of the episode [adjusted OR 3.0 (95% CI: 1.06-8.69)]. Conclusions: During non-urinary tract infections, the main use of temocillin was for LRTIs and IAIs due to ESBL-producing E. coli and K. pneumoniae. The main risk factor for failure was initial severity of the disease.

[Phage therapy: where do we stand?] / Traitement par bactériophages : où en est-on ?

PHAGE THERAPY: WHERE DO WE STAND? Bacteriophages, discovered at the beginning of the 20th century by Félix d'Hérelle, are viruses that infect and destroy bacteria. Unlike antibiotics, phages are specific to a given bacterial species. After initial successes (shigellosis, cholera), the arrival of antibiotics overshadowed phage therapy. It was not until 2000, with the emergence of antibiotic resistance, that phages and phage therapy made a comeback. They have the status of medicines, but production remains limited. In France, treatments are carried out on a compassionate basis, with a number of isolated successes that need to be confirmed by clinical trials. Some trials are currently underway in France to assess the efficacy of phage therapy in combination with antibiotics. France, a pioneer in phage therapy in its early days and at the time of its comeback, seems to be slowing down in 2024 compared with its European neighbors. The adoption of phage therapy on a routine basis in France will still require time and significant progress.

TRAITEMENT PAR BACTÉRIOPHAGES : OÙ EN EST-ON ? Les bactériophages, découverts au début du XXe siècle par Félix d'Hérelle, sont des virus qui infectent et détruisent les bactéries. Contrairement aux antibiotiques, les phages sont spécifiques d'une espèce bactérienne donnée. Après des premiers succès (shigellose, choléra), l'arrivée des antibiotiques a éclipsé la phagothérapie. Ce n'est qu'à partir de 2000, dans le contexte d'émergence de l'antibiorésistance, que les phages et la phagothérapie sont revenus sur le devant de la scène. Ils ont le statut de médicaments, mais leur production reste limitée. En France, des traitements sont réalisés dans le cadre d'accès compassionnels, avec de nombreux succès isolés nécessitant d'être confirmés par des essais cliniques. Certains essais sont en cours en France pour évaluer l'efficacité de la phagothérapie en association avec des antibiotiques. La France, pionnière de la phagothérapie à ses débuts et au moment de son retour, semble ralentir en 2024 par rapport à ses voisins européens. L'adoption de la phagothérapie en routine en France nécessitera encore du temps et des avancées significatives.

Impact of Clinical and Pharmacological Parameters on Faecal Microbiota Transplantation Outcome in Clostridioides difficile Infections: Results of a 5-Year French National Survey.

BACKGROUND: Detailed comparative assessment of procedure-related factors associated with faecal microbiota transplantation (FMT) efficacy in Clostridioides difficile infection (CDI) is limited. AIMS: We took advantage of the differences in procedures at the various French FMT centres to determine clinical and procedure-related factors associated with FMT success in CDI. METHODS: We performed a nationwide retrospective multicentre cohort study. All FMTs performed within The French Faecal Transplant Group for CDI from 2018 to 2022 were included. Clinical data were collected retrospectively from recipient medical files, characteristics of stool transplant preparations were prospectively collected by each Pharmacy involved. Univariate and multivariate analyses were performed using Fisher's test and multiple logistic regression. RESULTS: Six hundred fifty-eight FMTs were performed for 617 patients in 17 centres. The overall efficacy of FMT was 84.3% (520/617), with 0.5% of severe adverse events possibly related to FMT (3/658). Forty-seven patients were treated at the first recurrence of CDI with a similar success rate (85.1%). Severe chronic kidney disease (CKD; OR: 2.18, 95%CI [1.20-3.88]), non-severe refractory CDI (OR: 15.35, [1.94-318.2]), the use of ≥ 80% glycerol (OR: 2.52, [1.11-5.67]), insufficient bowel cleansing (OR: 5.47, [1.57-20.03]) and partial FMT retention (OR: 9.97, [2.62-48.49]) were associated with CDI recurrence within 8 weeks. CONCLUSIONS: Conditions of transplant manufacturing, bowel cleansing, and a route of delivery tailored to the patient's characteristics are key factors in optimising FMT efficacy. FMT at first recurrence showed high success in real-life practice, whereas it had lower efficacy in severe CDI and non-severe refractory CDI.

Use of frozen native feces for fecal microbiota transplantation in recurrent Clostridioides difficile infection: a simple way to improve the efficiency of donor feces preparation.

Preparing fecal microbiota transplants immediately after donation is resource-intensive, and a proportion are destroyed following abnormal screening results. We retrospectively compared two processes, frozen fecal preparation (FFP) and fresh native frozen preparation (FNFP), for clinical efficacy in the treatment of recurrent Clostridioides difficile infection (rCDI). FFP and FNFP were similarly effective with clinical success rates of 76.7% and 86.7% (P = 0.32), respectively. FNFP is an efficient procedure that saves resources while maintaining clinical efficacy in rCDI.

Treatment of persistent focalized Q fever: time has come for an international randomized controlled trial.

Q fever is a worldwide zoonosis due to Coxiella burnetii, responsible for endocarditis and endovascular infections. Since the 1990s, the combination hydroxychloroquine + doxycycline has constituted the curative and prophylactic treatment in persistent focalized Q fever. This combination appears to have significantly reduced the treatment's duration (from 60 to 26 months), yet substantial evidence of effectiveness remains lacking. Data are mostly based on in vitro and observational studies. We conducted a literature review to assess the effectiveness of this therapy, along with potential alternatives. The proposed in vitro mechanism of action describes the inhibition of Coxiella replication by doxycycline through the restoration of its bactericidal activity (inhibited in acidic environment) by alkalinization of phagolysosome-like vacuoles with hydroxychloroquine. So far, the rarity and heterogeneous presentation of cases have made it challenging to design prospective studies with statistical power. The main studies supporting this treatment are retrospective cohorts, dating back to the 1990s-2000s. Retrospective studies from the large Dutch outbreak of Q fever (>4000 cases between 2007 and 2010) did not corroborate a clear benefit of this combination, notably in comparison with other regimens. Thus, there is still no consensus among the medical community on this issue. However insufficient the evidence, today the doxycycline + hydroxychloroquine combination remains the regimen with the largest clinical experience in the treatment of 'chronic' Q fever. Reinforcing the guidelines' level of evidence is critical. We herein propose the creation of an extensive international registry, followed by a prospective cohort or ideally a randomized controlled trial.

Mutation Rate of AmpC ß-Lactamase-Producing Enterobacterales and Treatment in Clinical Practice: A Word of Caution.

In a retrospective multicenter study of 575 patients with bloodstream infections or pneumonia due to wild-type AmpC ß-lactamase-producing Enterobacterales, species with low in vitro mutation rates for AmpC derepression were associated with fewer treatment failures due to AmpC overproduction (adjusted hazard ratio, 0.5 [95% CI, .2-.9]). However, compared to cefepime/carbapenems, using third-generation cephalosporins as definitive therapy remained associated with this adverse outcome (15% vs 1%).

Postoperative infections after sinus lifts and onlay grafts in penicillin allergic patients.

INTRODUCTION: The primary objective of this retrospective study was to determine whether patients treated with clindamycin due to a reported allergy to penicillin have an increased risk of postsurgical infections after sinus lifts and onlay grafts. MATERIAL AND METHODS: A retrospective cohort study was performed on patients who underwent bone reconstruction procedures between October 2018 and December 2020. Data from all patients operated at the Pitié Salpêtrière University Hospital for sinus lifts or onlay grafts were collected. All surgical procedures studied were performed under preoperative and postoperative antibiotic prophylaxis with either amoxicillin (+/- clavulanic acid) or clindamycin for patients with reported penicillin allergy. Bone graft-associated infections as well as graft failures were recorded. RESULTS: In this study, 111 patients received bone reconstructions (89 sinus lifts and 148 onlay grafts). In the sinus lifts group, infections occurred in 5 of 89 sites (5.6 %). The infection rate was 28.5 % (7 graft sites) and only 3.9 % (82 graft sites) for clindamycin and for amoxicillin, respectively. In the onlay graft group, infections occurred in 25 of 148 sites (16.8 %). The infection rate was 56 % and only 12 % for clindamycin (18 graft sites) and for amoxicillin, respectively (130 graft sites). Non-Penicillin treated patients had a higher risk of infection with an odd ratio of 7.8 (95 % CI 1.1-54.8, P = 0.04) and 4.8 (95 % CI 1.9-12.3, P = 0.001) compared with patients receiving amoxicillin for onlay grafts and sinus lifts. CONCLUSION: Penicillin allergy and clindamycin use after sinus lift and onlay graft procedures were associated with a higher rate of infection and may be a risk factor for complications related to bone reconstruction surgery.

Fungal versus non-fungal supra-inguinal prosthetic vascular graft infections: A cohort study.

OBJECTIVES: Fungal prosthetic vascular graft infections are rare and mainly supra-inguinal. Current guidelines are based on the few studies that have specifically investigated this population, with few risk factors described. The objective of this study is to compare fungal and non-fungal supra-inguinal prosthetic vascular graft infections (PVGI), describing their specificities, identifying risk factors, and evaluating outcomes. PATIENTS AND METHODS: This is a single-center retrospective cohort study carried out at the Pitié-Salpêtrière Hospital in Paris, including all patients who were treated for a supra-inguinal PVGI between January 1st, 2009 and February 28th, 2021. Preoperative, intraoperative and postoperative data were compared between fungal and non-fungal PVGI. RESULTS: Out of the 475 patients screened, 148 developed a supra-inguinal PVGI: 32 fungal and 116 non-fungal. Factors independently associated with fungal PVGI were presence of a prostheto-digestive fistula (OR 5.98; 95% CI 2.29-15.62) and preoperative antibiotic therapy of seven days or more (OR 2.87; 95% CI 1.12-7.38). Mortality rate at 180 days was significantly higher for fungal as compared to non-fungal PVGIs (38% vs. 16% p = 0.009) and for fungal PVGI with prostheto-digestive fistula. However, there was no statistically significant relation between mortality due to prostheto-digestive fistula in contrast with fungal PVGI alone (p = 0.21). CONCLUSION: Prostheto-digestive fistula was strongly associated with fungal PVGI, which leads us to suggest that in such cases, an anti-fungal agent should be prescribed.

COVID-19 early curative treatments in kidney transplant recipients: is it really reasonable at the Omicron era?

Objective: Data about efficacy and safety of the latest COVID-19 treatments as nirmatrelvir/ritonavir (n/r) or Sotrovimab is scarce in solid organ transplant recipients in the Omicron era. This study aims at describing the outcome of kidney transplant recipients (KTRs) presenting Omicron infection according to their management: n/r, sotrovimab or no specific treatment. Patients and methods: We conducted a monocentric, retrospective observational study, including KTRs diagnosed Omicron infection between January and May 1st 2022 and compared their outcome (primary outcome defined as hospital admission for COVID-19 within a month after symptoms onset) according to early COVID-19 management. Results: Forty-five patients were included: 22 treated (12 n/r, 10 sotrovimab) and 23 with no specific treatment. The groups were statistically comparable. Two patients were admitted for COVID-19: one in each group, resulting in a non-different probability of the primary outcome at on month (p=0.9). Three patients presented tacrolimus overdose including two with acute kidney injury. Conclusions: There was no difference in outcome according to early therapeutic management: n/r, sotrovimab or no specific treatment. Our study both underlines a decreased severity of Omicron COVID-19 in KTRs (probably related to vaccinal immunity and decreased virulence of Omicron) and a potential severe adverse effects with n/r.

Objectif: Les données sur l'efficacité et la sécurité des derniers traitements de la Covid-19 sont peu nombreuses à l'ère du variant Omicron. Cette étude avait pour objectif de décrire l'évolution des transplantés rénaux (TR) présentant une infection à Omicron selon le traitement précoce reçu : nirmatrelvir/ritonavir (n/r), sotrovimab, ou pas de traitement. Patients et méthodes: Il s'agissait d'une étude monocentrique rétrospective observationnelle incluant tous les TR présentant une infection confirmée à Omicron entre le 1er janvier 2022 et le 1er mai 2022 et comparant leur évolution (critère de jugement principal : admission hospitalière pour Covid-19 à un mois du début des symptômes) selon leur prise en charge. Résultats: Quarante-cinq patients ont été inclus : 22 traités (12 n/r et 10 sotrovimab) et 23 non traités. Les groupes étaient statistiquement comparables. Seulement deux patients ont présenté le critère de jugement principal : un n/r et un non traité, avec une probabilité à un mois non différente (p = 0,9). Trois patients sur 12 ont en revanche présenté des surdosages en tacrolimus dans le groupe n/r, dont deux avec une insuffisance rénale aiguë. Conclusions: Dans les limites d'un petit effectif, nous n'avons pas montré de bénéfice au traitement précoce par n/r ou sotrovimab. On peut évoquer un effet de l'immunité vaccinale et une baisse de virulence du SARS-CoV-2. En revanche, les effets secondaires du n/r ne sont pas anodins avec des surdosages sévères malgré des protocoles de service précis. La balance bénéfice-risque de ces traitements doit être rediscutée.

Dalbavancin plasma concentrations in 133 patients: a PK/PD observational study.

OBJECTIVES: Limited pharmacokinetics data support dalbavancin long-term use in off-label indications and the optimal dosing regimen is debated. We aimed to describe dalbavancin concentrations in an observational retrospective multicentre study. METHODS: Patients from 13 French hospitals, treated with 1500 mg doses of dalbavancin and for whom therapeutic drug monitoring was performed from June 2018 to March 2021 were included. Dalbavancin plasma concentrations were described at peak and 1, 2, 3, 4, 6 and 8 weeks after the last 1500 mg dose. Concentrations in patients weighing more or less than 75 kg and with a GFR greater or less than 60 mL/min were compared. Microbiological data were collected and dalbavancin MIC was measured when possible. RESULTS: One hundred and thirty-three patients were included (69% treated for bone and joint infections, 16% for endocarditis). Thirty-five patients received a single dose of dalbavancin and 98 received several administrations. Two, 3 and 4 weeks after the last dose, median plasma concentrations were respectively 25.00, 14.80 and 9.24 mg/L for the first doses and 34.55, 22.60 and 19.20 mg/L for the second or subsequent doses. Weight and renal function had an impact on pharmacokinetics. Infection was documented in 105 patients (Staphylococcus spp. in 68% of cases). Staphylococcus aureus was isolated in 32.5% of cases (median MIC: 0.047 mg/L) and Staphylococcus epidermidis in 27% of cases (median MIC of 0.047 mg/L). CONCLUSIONS: Plasma concentrations of dalbavancin were consistent with those described in clinical trials and those sought during the industrial development of the molecule.

Effectiveness of third-generation cephalosporins or piperacillin compared with cefepime or carbapenems for severe infections caused by wild-type AmpC ß-lactamase-producing Enterobacterales: A multi-centre retrospective propensity-weighted study.

BACKGROUND: The optimal treatment regimen for infections caused by wild-type AmpC ß-lactamase-producing Enterobacterales remains controversial. This study compared the outcomes of bloodstream infections (BSI) and pneumonia according to the type of definitive antibiotic therapy: third-generation cephalosporin (3GC), piperacillin ± tazobactam, cefepime or carbapenem. METHODS: All cases of BSI and pneumonia caused by wild-type AmpC ß-lactamase-producing Enterobacterales over 2 years in eight university hospitals were reviewed. Patients who received definitive therapy consisting of either a 3GC (3GC group), piperacillin ± tazobactam (piperacillin group), or cefepime or a carbapenem (reference group) were included in this study. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was treatment failure due to infection by emerging AmpC-overproducing strains. Propensity-score-based models were used to balance confounding factors between groups. RESULTS: In total, 575 patients were included in this study: 302 (52%) with pneumonia and 273 (48%) with BSI. Half (n=271, 47%) received cefepime or a carbapenem as definitive therapy, 120 (21%) received a 3GC, and 184 (32%) received piperacillin ± tazobactam. Compared with the reference group, 30-day mortality was similar in the 3GC [adjusted hazard ratio (aHR) 0.86, 95% confidence interval (CI) 0.57-1.31)] and piperacillin (aHR 1.20, 95% CI 0.86-1.66) groups. The likelihood of treatment failure was higher in the 3GC (aHR 6.81, 95% CI 3.76-12.4) and piperacillin (aHR 3.13, 95% CI 1.69-5.80) groups. The results were similar when stratifying the analysis on pneumonia or BSI. CONCLUSION: Treatment of included BSI or pneumonia caused by wild-type AmpC ß-lactamase-producing Enterobacterales with 3GC or piperacillin ± tazobactam was not associated with higher mortality, but was associated with increased risk of AmpC overproduction leading to treatment failure compared with cefepime or a carbapenem.

Impact of clinical pharmacist interventions in a bone and joint infection orthoseptic surgery unit.

OBJECTIVES: To assess the impact of interventions of a clinical pharmacist in a unit of orthopedic surgery specialized in bone and joint infections. METHODS: Daily, in routine, a clinical pharmacist analyzed medication prescribed to inpatients via a computerized physician order entry (CPOE) (Phedra software). His attention was particularly focused on the impact of antibiotics on other medications. For this study, all of the pharmacist interventions (PI) have been retrospectively collected, then anonymized, and assessed over a two-month period. RESULTS: Thirty-eight patients were hospitalized during the study period, with a mean age of 63 years old. Forty-five interventions were identified which represents a mean of 1.18 pharmaceutical interventions per patient. Most of them concerned lack of follow-up (24%) and drug-drug interactions (22%) and widely non-anti-infectious medication (35 interventions) with levothyroxine (10 interventions) as the most involved non-anti-infectious molecule. Among antibiotics, with respectively 9 and 8 interventions, rifampicin and fluoroquinolones (6 interventions for moxifloxacin) were the most concerned notably for drug-drug interactions with usual treatment. CONCLUSION: In this observational retrospective study, 1.18 pharmacist interventions (PI) per patient were observed. Most of them are lack of follow-up and drug-drug interactions especially with usual treatment of patients. Moxifloxacin and rifampicin were the most antibiotics involved. Patients' characteristics (older, polypharmacy), long-term hospitalization and surgery are known to be predictive factors of medication errors and this study highlights the importance of the presence of clinical pharmacist in orthopedic surgery wards.

Severe Scabies: A French Multi-centre Study Involving 95 Patients with Crusted and Profuse Disease and Review of the Literature.

The aim of this multi-centre French retrospective study was to identify severe, i.e. crusted and profuse, scabies patients. Records were retrieved from 22 Dermatology or Infectious Diseases departments in the Ile-de-France from January 2009 to January 2015 to characterize epidemiology, demography, diagnosis, contributing factors, treatment features, and outcomes in severe scabies. A total of 95 inpatients (57 crusted and 38 profuse) were included. A higher number of cases was observed among elderly patients (>75 years), mostly living in institutions. Thirteen patients (13.6%) reported a history of previously treated scabies. Sixty-three patients (66.3%) had been seen by a previous practitioner for the current episode (up to 8 previous visits). Initial misdiagnosis (e.g. eczema, prurigo, drug-related eruptions, psoriasis) was documented in 41 patients (43.1%). Fifty-eight patients (61%) had already received 1 or more previous treatments for their current episode. Forty percent received corticosteroids or acitretin for an initial diagnosis of eczema or psoriasis. Median time from the onset of symptoms to the diagnosis of severe scabies was 3 months (range 0.3-22). Itch was present in all patients at diagnosis. Most patients (n=84, 88.4%) had comorbidities. Diagnostic and therapeutic approaches varied. Complications occurred in 11.5% of cases. To date, there is no consensus for diagnosis and treatment, and future standardization of is required for optimal management.

Pharmacokinetics/pharmacodynamics of ceftobiprole in patients on extracorporeal membrane oxygenation.

INTRODUCTION: Due to its bacteriological spectrum and efficacy in skin and soft tissue infections, ceftobiprole may be of interest for extracorporeal membrane oxygenation (ECMO) cannula-related infection. It is unknown whether ceftobiprole pharmacokinetics (PK) are changed by ECMO. METHODS: A retrospective monocentric cohort study was performed of 35 patients with suspected ECMO-related cannula infections (28 on ECMO, seven after ECMO removal), who received ceftobiprole as empiric treatment and had ceftobiprole blood levels measured at trough, peak and CT50 (50% of the dosing interval). Ceftobiprole blood levels of the 28 patients on ECMO were compared with those of the seven patients without ECMO. Factors associated with low ceftobiprole trough levels were also explored. RESULTS: Among the 35 patients included, 29 had a confirmed cannula-related infection and 48 pathogens were isolated. Ceftobiprole MIC was determined in 29 of these 48, and 23 (79%) were susceptible to ceftobiprole. Ceftobiprole blood levels (at trough, peak and CT50) were similar in ECMO and non-ECMO patients. Moreover, in patients whose pathogens responsible for infection were susceptible to ceftobiprole, 94% had a ceftobiprole trough level above the MIC. Ceftobiprole blood levels were decreased in patients with acute renal failure requiring renal replacement therapy (RRT) and in those with increased renal clearance (defined as creatinine clearance > 130 mL/min), independent of ECMO. No other factor was associated with modification of ceftobiprole PK/pharmacodynamics (PK/PD). CONCLUSIONS: The ceftobiprole PK/PD was no different in patients during ECMO or after its withdrawal. Factors associated with decreased ceftobiprole blood levels were patients requiring RRT and those with increased renal clearance.

Real-life temocillin use in Greater Paris area, effectiveness and risk factors for failure in infections caused by ESBL-producing Enterobacterales: a multicentre retrospective study.

Background: Temocillin is a ß-lactam that is not hydrolysed by ESBLs. Objectives: To describe the real-life use of temocillin, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure. Methods: Retrospective multicentric study in eight tertiary care hospitals in the Greater Paris area, including patients who received at least one dose of temocillin for ESBL infections from 1 January to 31 December 2018. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. A logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure. Results: Data on 130 infection episodes were collected; 113 were due to ESBL-producing Enterobacterales. Mean age was 65.2 ±â€Š15.7 years and 68.1% patients were male. Indications were mostly urinary tract infections (UTIs) (85.8%), bloodstream infections (11.5%), respiratory tract infections (RTIs) (3.5%) and intra-abdominal infections (3.5%). Bacteria involved were Escherichia coli (49.6%), Klebsiella pneumoniae (44.2%) and Enterobacter cloacae (8.8%). Polymicrobial infections occurred in 23.0% of cases. Temocillin was mostly used in monotherapy (102/113, 90.3%). Failure was found in 13.3% of cases. Risk factors for failure in multivariable analysis were: RTI (aOR 23.3, 95% CI 1.5-358.2) and neurological disease (aOR 5.3, 95% CI 1.5-18.6). Conclusions: The main use of temocillin was UTI due to ESBL-producing E. coli and K. pneumoniae, with a favourable clinical outcome. The main risk factor for failure was neurological disease.

Viral loads in clinical samples of men with monkeypox virus infection: a French case series.

BACKGROUND: Monkeypox virus (MPXV) is currently spreading among men who have sex with men, outside of sub-Saharan Africa, and close contact during sex seems to be one of the key pathways of viral transmission in the current outbreak. Our aim was to describe the distribution of MPXV in the human body, as it might play a role in its dissemination through sexual contact. METHODS: The study population in this case series consisted of patients with confirmed MPXV infection attending the Pitié-Salpêtrière Hospital (Paris, France), who had been sampled from multiple anatomical sites, including skin, anus, throat, blood, urine, and semen, at diagnosis and 2 weeks later. We compared the proportion of positive samples and MPXV viral loads (given as PCR cycle thresholds [Ct]) between anatomical sites, and between day 0 (D0) and D14. FINDINGS: Overall, 356 samples were collected between May 20 and June 13, 2022, from 50 men with a median age of 34 years (IQR 29-40). 22 (44%) of the 50 men were classified as HIV-negative on day (D)0, and 22 (44%) were living with HIV. At D0, MPXV detection was more frequent from skin (44 [88%] of 50), anus (30 [71%] of 42), and throat (36 [77%] of 47) than from blood (13 [29%] of 45), urine (nine [22%] of 41), or semen (13 [54%] of 24). Viral loads were significantly higher from skin lesions (Ct 19·8) and anal samples (Ct 20·9) than from throat (Ct 27·2), blood (Ct 32·8), urine (31·1), or semen samples (Ct 27·8). When analysing the 107 samples taken from 24 patients at D14, the proportion of positive samples strongly decreased between D0 and D14 at all sites: skin (four [22%] of 18), anus (two [9%] of 22), throat (none of 21), blood (one [5%] of 21), urine (none of 14), and semen (two [9%] of 11). INTERPRETATION: These data contribute to a better understanding of how the virus might spread between sexual partners over a relatively short period of time. High MPXV viral loads from skin and mucosa, including genital and anal sites, suggest that transmission most likely occurs through direct body contact rather than through the respiratory route or contact with body fluids, which should help to refine the prevention messages delivered to individuals most exposed to the virus. FUNDING: None.