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Bone and joint infections (BJI) are one of the most difficult-to-treat bacterial infection, especially in the era of antimicrobial resistance. Lytic bacteriophages (phages for short) are natural viruses that can selectively target and kill bacteria. They are considered to have a high therapeutic potential for the treatment of severe bacterial infections and especially BJI, as they also target biofilms. Here we report on the management of a patient with a pandrug-resistant Pseudomonas aeruginosa spinal abscess who was treated with surgery and a personalized combination of phage therapy that was added to antibiotics. As the infecting P. aeruginosa strain was resistant to the phages developed by private companies that were contacted, we set up a unique European academic collaboration to find, produce and administer a personalized phage cocktail to the patient in due time. After two surgeries, despite bacterial persistence with expression of small colony variants, the patient healed with local and intravenous injections of purified phages as adjuvant therapy. Here, the authors describe a patient with a pandrug-resistant Pseudomonas aeruginosa spinal abscess successfully treated with a personalized combination of phage therapy and antibiotics.

BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age ( P =0.028), unrelated donor ( P =0.0178), stem cell source ( P =0.0001), HLA mismatching ( P =0.0022) and BU in conditioning regimen ( P =0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) ( P =0.0005) and peripheral blood stem cells ( P =0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity ( P =0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization ( P <0.0001), more RBC ( P =0.0003) and platelet transfusions ( P <0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at €2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

Abstract Background Prospective data on the natural history of anal human papillomavirus (HPV) infection are scarce in human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). Methods We analyzed incidence and clearance of HPV-16 and HPV-18 in a French cohort of HIV-infected MSM, aged ≥35 years, followed-up annually (n = 438, 2014–2018). Results Human papillomavirus-16 and HPV-18 incidence were similar (~10% incident infections at 24 months). Human papillomavirus-16 incidence was higher among high-grade versus no lesion at baseline (adjusted incidence rate ratio = 3.0; 95% confidence interval, 1.07–8.18). Human papillomavirus-16 cleared significantly slower than HPV-18 (32% versus 54% by 24 months). Conclusions In conclusion, anal HPV-16 is more persistent than HPV-18, and its incidence correlates with a prior detection of high-grade lesions. We analyzed incidence and clearance of HPV-16 and HPV-18 in a French cohort of HIV-infected MSM. HPV-16 and HPV-18 incidence were similar, whereas HPV-16 clearance was slower than HPV-18. Finally, HPV-16 incidence correlated with a prior detection of high-grade lesions.

Abstract Background We assessed prevalence and risk factors for anal human papillomavirus (HPV) in human immunodeficiency virus (HIV)–positive men who have sex with men (MSM), who are at high-risk of HPV-related anal cancer. Methods APACHES is a multicentric, prospective study of anal HPV infection and lesions in HIV-positive MSM aged ≥35 years. At baseline, participants underwent anal swabs for HPV and cytology, plus high-resolution anoscopy. High-risk HPV (HR-HPV) was tested by Cobas4800, with genotyping of HR-HPV positives by PapilloCheck. Results Among 490 participants, prevalence of HPV16 and HR-HPV was 29% and 70%, respectively, and did not differ significantly by age, sexual behavior, or markers of HIV or immune deficiency. Smoking was the only, albeit weak (odds ratio, 1.8; 95% confidence interval, 1.2–2.7), predictor of HR-HPV. High-risk HPV and HPV16 prevalence increased strongly with anal diagnosis severity, both by worse cytological/histological (composite) diagnosis at APACHES baseline and worse historical diagnosis. HPV16 rose from 19% among participants who were negative for lesions to 63% among participants with high-grade lesions. In contrast, non-HPV16 HR-HPVs were less prevalent in high-grade (37%) than negative (64%) composite diagnosis, and their causal attribution was further challenged by multiple HPV infections. Conclusions Human papillomavirus 16 is ubiquitously frequent among human immunodeficiency virus -positive men having sex with men, and more strongly associated with high-grade anal lesions than other high-risk types, confirming it as a target for anal cancer prevention. Baseline findings of this multicentric cohort in France highlight that human pappilomavirus 16 (HPV16) prevalence is ubiquitously high among human immunodeficiency virus–positive men who have sex with men and more strongly associated with high-grade anal lesions than other high-risk human papillomavirus types, confirming it as a target for anal cancer prevention.

Purpose To evaluate the contribution of ultrasound in the management of ballistic peripheral nerve injuries (BPNI). Methods Twenty-five Armenian soldiers who sustained BPNI of 44 different nerves during the Second Nagorno-Karabakh War in 2020 benefited from multidisciplinary team management including ultrasound examination. Results The injuries affected the upper limb in 17 cases (including 2 bilateral cases), the lower limb in 7 cases and both upper and lower limb in 1 case. The injuries were due to shrapnel in 14 cases and to high-velocity bullets in 10 cases. One median-radial nerve injury occurred after prolonged haemostatic tourniquet. Thirteen patients had at least 2 nerves injuries. Ultrasound showed 16 nerves with neurapraxia, including 2 blast injuries, 8 axonotmesis with a neuroma-in-continuity and 8 neurotmesis. Twelve soldiers got surgery prior to our missions. The preoperative skin marking of nerve lesions under ultrasound control was very useful for the surgeon during the operation. A good correlation with surgery was observed, in 7 cases, and in 10 cases, a correlation with electroneuromyography (ENMG) was found. The ultrasound exploration was not informative in 2 patients. Conclusion Ultrasound is a useful examination for the assessment of BPNI. It allows exploration of the entire nerve without artefact in the presence of projectiles or external fixator, contrary to MRI. It localizes and characterizes the nerve damage with a good correlation with data from the surgery and ENMG. Clinical relevance statement Ballistic wounds of peripheral nerves are frequent in war wounded. Ultrasound can localize and characterize nerve injuries with good correlation with surgical and electrophysiological data.

To evaluate factors associated with failure in patients treated with DAIR (debridement, antibiotic therapy, and implant retention) for Staphylococcus aureus prosthetic joint infections (PJIs). We retrospectively analyzed consecutive patients with stable PJI due to S. aureus treated with DAIR at six hospitals between 2010 and 2014. Cox proportional hazards regression was used to study factors associated with treatment failure at 2 years. Of 154 eligible patients, 137 were included (mean age 73 ± 13 years; male 56%). The estimated success rate according to the Kaplan–Meier method was 76.2 [95% CI 68–83] at 2 years of follow-up. In multivariate analysis, longer duration of treatment (hazard ratio (HR) 0.78 [0.69–0.88]; p < 0.001) and combination therapy including rifampin (HR 0.08 [0.018–0.36]; p = 0.001) were independently associated with success, whereas active smoking was independently associated with failure (HR 3.6 [1.09–11.84]; p = 0.036). When the analysis was restricted to patients with early infection onset (< 3 months), early acute infection was also predictive of a better prognosis (HR 0.25 [0.09–0.7]; p = 0.009). Failure was not associated with time from prosthesis insertion to debridement, nor with duration of symptoms > 3 weeks and type of prosthesis (hip or knee). These results remained unchanged when the 14 patients under immunosuppressive therapy were removed from analysis. These data suggest that DAIR can be performed even if infection and symptoms are delayed but reserved to patients who are able to follow rifampin-based combination therapy for a prolonged duration that should not be different for hip and knee PJI.

Ceftaroline fosamil is approved for the treatment of complicated skin and soft tissue infections (cSSTI) and community-acquired pneumonia (CAP); however, data on its real-world use and effectiveness in Europe and Latin America are currently limited. This retrospective observational study assessed ceftaroline fosamil use and treatment outcomes in adults hospitalized with cSSTI or CAP treated with ceftaroline fosamil in a usual care setting in Europe and Latin America. Results for patients with cSSTI are reported. Data from patients with cSSTI who received ≥4 consecutive intravenous ceftaroline fosamil doses up to May 31, 2019, were collected from sites in Brazil, Colombia, France, Greece, Italy, and Spain. Patient characteristics, clinical management, hospitalization information, microbiological diagnosis, and clinical responses were summarized descriptively. Healthcare resource use variables were evaluated by clinical response to ceftaroline fosamil. Data for 132 patients were included (58.3% male; mean age 58.5 years). Most common lesions were cellulitis/fasciitis (62.1%), abscess (34.1%), and post-surgical wounds (19.7%). Pathogens most frequently identified were methicillin-resistant (18.2%) and methicillin-susceptible (17.4%). Median (range) ceftaroline fosamil treatment duration was 8 (2-60) days (daily doses of 1200 [400-2400] mg); 78 patients (59.1%) received monotherapy. In total, 75 (56.8%) patients had additional antibiotics after ceftaroline fosamil. Clinical response occurred in 118 (89.4%) patients. All-cause 30-day readmission occurred in 13 (9.8%) patients, and all-cause 30-day mortality in 7 (5.3%). Clinical response to ceftaroline was associated with >25% shorter length of hospital and intensive care stay, and with ~40% lower hospital costs, versus non-responders. Ceftaroline fosamil was effective in treating adults with cSSTI and clinical response to ceftaroline fosamil was associated with reductions in healthcare resource use compared with non-responders, in Europe and Latin America. NCT04198571.

During prosthetic joint infection (PJI), optimal surgical management with exchange of the device is sometimes impossible, especially in the elderly population. Thus, prolonged suppressive antibiotic therapy (PSAT) is the only option to prevent acute sepsis, but little is known about this strategy. We aimed to describe the characteristics, outcome and tolerance of PSAT in elderly patients with PJI. We performed a national cross-sectional cohort study of patients >75 years old and treated with PSAT for PJI. We evaluated the occurrence of events, which were defined as: (i) local or systemic progression of the infection (failure), (ii) death and (iii) discontinuation or switch of PSAT. A total of 136 patients were included, with a median age of 83 years [interquartile range (IQR) 81–88]. The predominant pathogen involved was Staphylococcus (62.1%) ( Staphylococcus aureus in 41.7%). A single antimicrobial drug was prescribed in 96 cases (70.6%). There were 46 (33.8%) patients with an event: 25 (18%) with an adverse drug reaction leading to definitive discontinuation or switch of PSAT, 8 (5.9%) with progression of sepsis and 13 died (9.6%). Among patients under follow-up, the survival rate without an event at 2 years was 61% [95% confidence interval (CI): 51;74]. In the multivariate Cox analysis, patients with higher World Health Organization (WHO) score had an increased risk of an event [hazard ratio (HR) = 1.5, p  = 0.014], whereas patients treated with beta-lactams are associated with less risk of events occurring (HR = 0.5, p  = 0.048). In our cohort, PSAT could be an effective and safe option for PJI in the elderly.

Nocardiosis is a life-threatening opportunistic infection in immunocompromised patients. Herein, we present successful adjunctive use of liposomal nebulized amikacin and tedizolid in a recipient of allogeneic hematopoietic stem cell transplantation infected with Nocardia nova complex who presented multiple complications to conventional therapeutic options.

Background. Staphylococcus aureus superantigens are associated with the pathogenesis of toxic shock syndrome, but their involvement in septic shock is unknown. Methods. We compared the distribution of 11 superantigen genes in S. aureus blood culture isolates obtained from patients with sepsis who did and did not have septic shock (19 and 61 patients, respectively), as well as from patients with suppurative infections (101 patients) and patients with colonization (25 patients). Results. The prevalence of the enterotoxin A gene (sea) increased significantly with the severity of infection (P < .001), whereas the prevalence of the enterotoxin gene cluster (egc) decreased significantly (P = .009). Conclusion. Enterotoxin A (SEA) might play a key role in sea-positive S. aureus sepsis by triggering over-expression of inflammatory mediators associated with shock. Novel treatments targeting superantigens, especially the sea gene, might be beneficial in the treatment of S. aureus sepsis.