Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection.

BACKGROUND: The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear. METHODS: We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points. RESULTS: A total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events. CONCLUSIONS: Among patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.).

Efficacy and safety of co-trimoxazole in device-related bone and joint infections: a CRIOGO multicentre case-control study.

OBJECTIVES: Co-trimoxazole could be an alternative antibiotic to treat device-related bone and joint infection (BJI) but there are few published data about its efficacy and safety in this complex scenario to treat infection. The objective was to compare the outcome of patients with device-related BJI treated with an antibiotic regimen including co-trimoxazole versus a regimen without co-trimoxazole. METHODS: This multicentre case-control study included consecutive adult patients diagnosed with device-related BJI. Each patient receiving co-trimoxazole was included in the co-trimoxazole group and was matched with two control patients, with stratification on microbial aetiology and age. The primary outcome was composite and defined by death or treatment failure during the follow-up. RESULTS: In this study, 150 patients were included, 50 in the co-trimoxazole group and 100 in the control group. The rate of reaching the primary endpoint was 18% in the co-trimoxazole group (9/50 cases) versus 21% in the control group (21/100) (P = 0.66). Co-trimoxazole use was not associated with an unfavourable outcome in the multivariate analysis (adjusted OR 0.8, 95% CI 0.31-2.06, P = 0.64). Although no significant difference was observed in premature discontinuation of treatment due to an adverse event between both groups (14 versus 12%, P = 0.73), treatment-related adverse events were significantly more frequently reported in patients of the co-trimoxazole group than the control group [34% (17/50) versus 18% (18/100), P = 0.03]. CONCLUSIONS: Co-trimoxazole appears to be an effective alternative for the treatment of BJI, even when it occurs on a device, but the safety profile requires close monitoring of adverse effects.

Impact of Enterococcus faecalis Endocarditis Treatment on Risk of Relapse.

BACKGROUND: Enterococcus faecalis infective endocarditis (EFIE) is characterized by a higher frequency of relapses than other infective endocarditis. The role of the treatment on its occurrence remains poorly understood. The aim of this study was to investigate whether the antibiotic regimen could impact the risk of relapse in EFIE. MATERIALS: This was a multicenter retrospective study of patients diagnosed with definite EFIE between 2015 and 2019 in 14 French hospitals. The primary endpoint was the occurrence of relapses within the year following endocarditis diagnosis. As death was a competing risk for relapse, Fine and Gray models were used for studying risk factors and impact of treatment. RESULTS: Of the 279 patients included, 83 (29.7%) received the amoxicillin-gentamicin (A-G) combination, 114 (40.9%) amoxicillin-ceftriaxone (A-C), 63 (22.6%) A-G and A-C (A-G/A-C) sequentially, 9 (3.2%) amoxicillin (A), and 10 received other treatments. One-year-relapse rate was 9.3% (26 patients). Relapse occurred after a median delay of 107 days from EFIE diagnosis; 6 occurred after 6 months, and 6 were diagnosed by blood cultures in asymptomatic patients. In multivariate analysis, surgery during treatment was a protective factor against one-year relapse and death.The cumulative incidence of relapse 1 year after endocarditis was 46.2% for patients treated with amoxicillin, 13.4% with A-G, 14.7% with A-C, and 4.3% with A-G/A-C (P≥.05 in multivariate analysis). CONCLUSIONS: Relapses after treatment of EFIE are frequent, frequently asymptomatic, and may occur more than 6 months after the initial episode.

Are unknown co-medications, over-the-counter and off-label drug use still problems among people living with HIV? Results from a transversal survey in 23 centres in France.

INTRODUCTION: Polypharmacy can lead to drug-drug interactions (DDIs), especially with ART. The burden of co-medications, including over-the-counter (OTC) drugs and self-medications, could be underestimated. We aimed to investigate the proportion of people living with HIV (PLHIV) with declared and undeclared co-medications, as well as their potential burden. METHODS: We conducted a national, multicentre, 1 week cross-sectional study between 10 December and 16 December 2019 in 23 French hospitals amongst consecutive adult PLHIV presenting for a routine outpatient visit. A standardized questionnaire filled in by the physicians assessed all medications and other active chemical substances taken by the PLHIV. RESULTS: Overall we enrolled 496 participants from 23 centres. Median age was 50.6 years; ART regimens included an integrase inhibitor in 61% (n = 302), an NNRTI in 34% (n = 169) and a PI in 14% (n = 70) of the cases. Co-medications involved 392 (79%) PLHIV, among which 85 (17%) received polypharmacy (≥5 medications). Previously unknown co-medications or other active substances were found for 32% (n = 159) of the participants. Corticosteroids (9%, n = 46) and proton pump inhibitors (10%, n = 50) were frequently administered. These co-medications did not differ according to age range. Illegal drug use was declared by 11% (n = 54) and OTC drugs by 23% (n = 113) of PLHIV. Potential DDIs were discovered for 11% (n = 53), leading to treatment modifications in 47% (25/53) of cases. CONCLUSIONS: Potential DDIs that lead to therapeutic modifications remain significant whatever the age of PLHIV. More devoted time to identify co-medications and OTC treatment is needed in all PLHIV.

Tenofovir disoproxil fumarate and emtricitabine maintenance strategy in virologically controlled adults with low HIV-1 DNA: 48 week results from a randomized, open-label, non-inferiority trial.

OBJECTIVES: Low HIV reservoirs may be associated with viral suppression under a lower number of antiretroviral drugs. We investigated tenofovir disoproxil fumarate/emtricitabine as a maintenance strategy in people living with HIV (PLHIV) with low HIV-DNA. METHODS: TRULIGHT (NCT02302547) was a multicentre, open-label, randomized trial comparing a simplification to tenofovir disoproxil fumarate/emtricitabine versus a triple regimen continuation (tenofovir disoproxil fumarate/emtricitabine with a third agent, control arm) in virologically suppressed adults with HIV-DNA <2.7 log10 copies/106 PBMCs and no prior virological failure (VF). The primary endpoint (non-inferiority margin 12%) was the percentage of participants with a plasma viral load (pVL) <50 copies/mL in ITT (Snapshot approach) and PP analyses at Week 48 (W48). RESULTS: Of the 326 participants screened, 223 (68%) were randomized to the tenofovir disoproxil fumarate/emtricitabine arm (n = 113) or control arm (n = 110). At W48, the tenofovir disoproxil fumarate/emtricitabine and control arms maintained a pVL < 50 copies/mL in 100/113 (88.5%) and 100/110 (90.9%) participants, respectively (ITT difference 2.4%, 95% CI -5.9 to 10.7; PP difference 3.4%, 95% CI -4.2 to 11.0). Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI -1.9 to 9.4). All VFs were resuppressed after treatment modification. CONCLUSIONS: Although non-inferiority was shown, simplification to tenofovir disoproxil fumarate/emtricitabine should not be used for most PLHIV because of a low risk of VF with resistance.

Low-level HIV viremia is associated with low antiretroviral prescription refill rates and social deprivation.

Optimal management of patients experiencing persistent low-level viremia (LLV) remains challenging and poorly understood. This study aimed to assess the association between poor antiretroviral treatment (ARV) adherence and persistent LLV. ADHELOW is a sub-study of the ECHEC cohort comprising HIV-infected adults with virological failure (viral load>50 copies/mL). Patients were recruited in 2013-2015 from 4 French university hospitals. Those with LLV (i.e., ≥2 viral load measurements between 50 and 500 copies/mL) were selected and matched on age and sex to 3 controls with virological suppression. The adherence rate was estimated using pharmacy-delivered prescription refills over one year. Overall, 60 patients were included (15 LLV and 45 controls). Mean age was 50.20 years, M/F sex ratio was 14 and mean EPICES (social deprivation) score was 42.90. In univariable analyses, LLV patients had significantly lower adherence (<80%: 53.30% vs. 6.67%, p < 0.01) and were more likely to have an EPICES score >40.2 (60.00% vs. 24.44%, p < 0.01). In multivariable analysis, these two variables remained significantly associated with LLV (OR 31.49, CI 95% [4.54-218.70]) and OR 11.00 (CI 95% [1.87-218.70], respectively). Poor long-term treatment adherence, estimated by prescription refills, was strongly associated with LLV. This reinforces the message that adherence counseling should be the primary intervention to overcome LLV.

First description of bacteremia caused by Oscillibacter valericigenes in a patient hospitalized for leg amputation.

Initially isolated from the alimentary canal of a Japanese corbicula clam, Oscillibacter valericigenes is a Gram-negative rod, of which culture remains very difficult. Herein we present the first case of bacteremia due to Oscillibacter valericigenes, in humans. A 55-year-old man was hospitalized for clinical management of multiple neglected leg wounds (colonized with maggots) that had occurred during a motorcycle accident. Following radiological confirmation of the bone infection, a transfemoral amputation was performed to limit the risk of extended infection. During hospitalization, before the amputation, the patient experienced fever, biological inflammation justifying the sampling of multiple blood cultures. Anaerobic blood culture was positive after 34 hours, without identification by routine procedure (MALDI-TOF), justifying identification by 16S DNA sequencing. In the absence of possible subculture, antibiotic sensitivity testing could not be performed. A pre-emptive treatment by piperacillin-tazobactam was introduced for 14 days. The evolution was good, except for a local disunion. Complete phylogenic analysis of the clinical strain showed that it significantly differed from the reference strain, which is distantly related to the Clostridia cluster IV. Due to the culture conditions and specialized identification method by sequencing, prevalence of O. valericigenes may be underestimated. Optimization of blood culture procedures and utilization of 16S rRNA gene sequencing are tools needed for identification of rare pathogens that could help to optimize clinical management of infected patients.

Dolutegravir Monotherapy Versus Dolutegravir/Abacavir/Lamivudine for Virologically Suppressed People Living With Chronic Human Immunodeficiency Virus Infection: The Randomized Noninferiority MONotherapy of TiviCAY Trial.

BACKGROUND: We investigated whether dolutegravir (DTG) monotherapy could be used to maintain virological suppression in people living with human immunodeficiency virus (HIV) on a successful dolutegravir-based triple therapy. METHODS: MONCAY (MONotherapy of TiviCAY) was a 48-week, multicentric, randomized, open-label, 12% noninferiority margin trial. Patients with CD4 nadir >100/µL, plasma HIV-1 RNA <50 copies/mL for ≥12 months, and stable regimen with DTG/abacavir (ABC)/lamivudine (3TC) were 1:1 randomized to continue their regimen or to DTG monotherapy. The primary endpoint was the proportion of patients with HIV RNA <50 copies/mL at week 24 in intention-to-treat snapshot analysis. Virologic failure (VF) was defined as 2 consecutive HIV RNA >50 copies/mL within 2 weeks apart. RESULTS: Seventy-eight patients were assigned to DTG monotherapy and 80 to continue DTG/ABC/3TC. By week 24, 2 patients in the DTG group experienced VF without resistance to the integrase strand transfer inhibitor (INSTI) class; 1 patient discontinued DTG/ABC/3TC due to an adverse event. The success rate at week 24 was 73/78 (93.6%) in the DTG arm and 77/80 (96.3%) in the DTG/ABC/3TC arm (difference, 2.7%; 95% confidence interval [CI], -5.0 to 10.8). During subsequent follow-up, 5 additional VFs occurred in the DTG arm (2 of which harbored emerging resistance mutation to INSTI). The cumulative incidence of VF at week 48 was 9.7% (95% CI, 2.8 to 16.6) in the DTG arm compared with 0% in the DTG/ABC/3TC arm (P = .005 by the log-rank test). The Data Safety Monitoring Board recommended to reintensify the DTG arm with standardized triple therapy. CONCLUSIONS: Because the risk of VF with resistance increases over time, we recommend avoiding DTG monotherapy as a maintenance strategy among people living with chronic HIV infection. CLINICAL TRIALS REGISTRATION: NCT02596334 and EudraCT 2015-002853-36.

Nebulized Liposomal Amphotericin B for Treatment of Pulmonary Infection Caused by Hormographiella aspergillata: Case Report and Literature Review.

Invasive fungal infection is a serious complication following allogeneic hematopoietic stem cell transplantation. Pulmonary infection due to Hormographiella aspergillata is an uncommon condition associated with a high mortality rate. The susceptibility of H. aspergillata to available antifungal agents is not well established. We report for the first time a case of H. aspergillata lung infection that responded poorly to conventional treatment with liposomal amphotericin B (LAmB; 3 mg kg-1 of body weight per day) with renal damage at higher posology (5 mg kg-1 of body weight per day), but improved rapidly after addition of nebulized LAmB to intravenous LAmB (3 mg kg-1 of body weight per day). Successful treatment of our patient using nebulized LAmB would be worth evaluating in cases refractory to standard treatment or when the reference treatment may not be extended due to interaction or side effects.

Reliability of the INSTI® rapid test for the diagnosis of HIV-1 non-B subtypes and recombinant variants.

Data regarding the efficacy of Rapid HIV tests (RHTs) in detecting non-B subtype HIV-1 are limited. We evaluated the sensitivity of the INSTI® test for the detection of HIV-1 antibodies for the diagnosis of HIV-1 non-B subtypes and recombinant variants. We identified adults with HIV-1 infection due to non-B subtypes and recombinant variants. The participants were re-tested with INSTI® test. We included 258 patients. Overall, the INSTI® test sensitivity was 98.4% (95%CI: 96.9-99.9%). For the major CRF_02AG subtype, the sensitivity was 99.0% (95%CI: 97.1-100%). The HIV INSTI® test is reliable for the detection of various non-B HIV-1 antibodies.

Immuno-virological and clinical impacts of treating cancer in patients living with HIV.

BACKGROUND: Patients living with HIV (PLHIV) are increasingly being affected by cancer. However, data evaluating the long-term impact of cancer treatment on HIV course are sparse. METHODS: To determine whether anticancer treatments detrimentally impact HIV course, we conducted a retrospective cohort study in seven hospitals in France. Adult PLHIV treated for haematological or solid malignancies were included and compared (1:1) with suitably matched (cancer-free) controls. The primary outcome was the risk of a ≥ 25% reduction in the absolute CD4+ count during follow-up. The risks for virological failure (i.e. a confirmed plasma viral load >50 copies/mL), incidental AIDS-related illnesses and death over time were also assessed. Multivariate Cox proportional-hazards regression analyses were used to identify the outcome predictors. RESULTS: One-hundred-and-ten patients with cancer and 110 controls were followed for a median of 4.4 years. In a Cox model, the CD4+ depletion was strongly predicted by external radiotherapy (ERT) exposure (HR = 5.1, 95% CI, 3.0-8.6, P < 0.0001) but not by chemotherapy. For patients exposed to ERT, the magnitude of the CD4+ depletion peaked 6 months after their cancer diagnosis (mean CD4+ drop at this time =  -283 ± 370 cells/mm(3)). Overall, the cancer patients were also more likely to experience virological failure than the controls (HR = 1.7, 95% CI, 1.1-2.7, P = 0.03). Finally, the incidence of AIDS-related illnesses was similar for both groups. CONCLUSIONS: In PLHIV, cancer treatment increased the risk for prolonged CD4+ depletion and virological failure but had no impact on AIDS-related events when appropriate prophylaxes were implemented.

Nebulised liposomal amphotericin B for Aspergillus lung diseases: case series and literature review.

Over the past 10 years the incidence of Aspergillus spp. has significantly increased, and it is now the most widespread air transmission fungal pathogen in developed countries. Whatever the clinical expression of the pulmonary disease and despite recent progress in antifungal drug therapy, morbidity and mortality related to aspergillosis lung disease still constitute a serious threat for immunosuppressed or mildly immunocompromised patients. Moreover, the treatments currently used have many limitations due to adverse effects and drug interactions. Finally, subjects exposed to azoles present an increased risk of Aspergillus-resistant strain emergence. We have reported five cases with aspergillosis lung diseases that were either difficult to control or in which patients had a contra-indication to triazole therapy, but which showed durable improvement following the administration of nebulised liposomal amphotericin B. Our alternative strategy could be of interest for patients with aspergillosis lung disease who otherwise cannot be conventionally treated by triazoles.

Pneumocystis jirovecii pneumonia in HIV-negative patients: a prospective study with focus on immunosuppressive drugs and markers of immune impairment.

Pneumocystis jirovecii pneumonia (PCP) is emerging in HIV-negative patients, for whom the prognosis is significantly worse than in HIV-infected patients and risk factors are poorly characterized. We performed an observational, multi-centre, prospective study of 56 consecutive cases of documented PCP in HIV-negative patients, and found that: (1) the main underlying conditions were haematological malignancies (43%), solid tumours (25%), inflammatory diseases (20%), and solid organ transplantation (7%); (2) most patients (80%) had received prolonged corticosteroids, with a mean daily dose of 47.3 ± 32.8 mg equivalent prednisone when PCP was diagnosed, and a mean cumulative dose of 5807 ± 5048 mg over the last 12 months; and (3) the median CD4 cell count was 0.12 × 109/l (range 0.0-1.42), with a median CD4/CD8 ratio of 1.32 (0.0-6.4). These findings may be used to better target PCP prophylaxis according to the level of risk and contribute to decrease the burden of PCP in HIV-negative patients.

Management of urosymphyseal fistula and pubic bone osteomyelitis: Description of a new surgical technique by cystectomy, urinary diversion and pelvic filling flap by unilateral pedicled myocutaneous vertical rectus abdominus muscle flap.

Pubic bone osteomyelitis is a rare infection, mostly related to urinary fistula. The published data about the medical or surgical management of this type of infection is relatively poor. In this case study of three patients, we describe our surgical technique for the management of urosymphyseal fistula complicated with pubic bone infection using pelvic filling flap by unilateral pedicled myocutaneous vertical rectus abdominus muscle flap. The first patient had the pelvic space filled with omentum flap. Unfortunately, the patient presented, postoperatively, an enteric fistula resulting from intestine incarceration on the resected bone. Considering this failure, the next two cases, have benefited from a Taylor flap to protect the peritoneal cavity by covering the residual pubic bone. Early complications were pyelonephritis and anemia (Clavien-Dindo 2), but no repeat surgery was required afterwards. The hospital stay for both cases were 26- and 12-days contrary to the first case who was hospitalized for 180-days. In conclusion, despite our limited experience in managing complicated urosymphyseal fistula, Taylor's flap, mainly used for gynecological or rectal surgery, might be a good reproducible solution for the surgical management of this kind of fistula with pubic debridement. It allows to protect the peritoneal cavity with fewer postoperative complications.

Acceptability determinants of a proposal to reduce antiretroviral treatment to an oral two-drug regimen among patients living with HIV and physicians in France.

An oral two-drug regimen (O2DR) in the form of a once-a-day single tablet is now recommended for treatment switching and treatment initiation for HIV. In clinical care, the process of treatment change refers to adaptation issues, both individual and within the care relationship. The study aim is to present the determinants involved in the acceptability of switching to O2DR in the PROBI (Patient-Reported Outcomes BItherapy) qualitative study. The study includes 30 interviews: 15 were conducted with doctors caring for people living with HIV, 15 were conducted with patients who had been offered a change of treatment. A double analysis was carried out: lexicometric analysis to highlight the structuring of the discourse around the change in treatment and a thematic analysis to understand the associated issues more precisely. The results highlighted common concerns with respect to switching to O2DR. Also, the caregiver-patient relationship was a central determinant in treatment switching. Information, knowledge and representations of O2DR are also factors facilitating treatment change and should be taken into account for doctors' and patients' adherence.

Long-term antiretroviral therapy initiated during primary HIV-1 infection is key to achieving both low HIV reservoirs and normal T cell counts.

OBJECTIVES: To characterize viro-immunological outcomes following long-term combined antiretroviral therapy (cART) initiated during primary HIV infection (PHI) or chronic HIV infection (CHI) and to identify factors predictive of optimal viro-immunological responder (OVIR) status. METHODS: This was a prospective, single-centre cohort study of HIV-1-infected patients on effective cART. Total cell-associated HIV DNA levels and T cell counts before and during treatment were used to identify factors predictive of OVIR status {i.e. low HIV DNA level [<2.3 log10 copies/10(6) peripheral blood mononuclear cells (PBMCs)], together with normalization of the absolute/relative CD4+ T cell counts and CD4+/CD8+ ratio}. RESULTS: A total of 307 patients were enrolled, of whom 35 started cART during PHI (<4 months post-infection) and 272 during CHI. HIV DNA decay was modelled with a non-linear mixed-effects model that showed two phases of HIV DNA decay, both of which were significantly more pronounced in the PHI group. At the end of follow-up, after a median of 4 years of viral suppression (<50 copies/mL), HIV DNA levels were lower in the PHI group than in the CHI group (median = 2.15 versus 2.84 log10 copies/10(6) PBMCs; P< 0.0001). Immune reconstitution was more rapid and sustained in the PHI group (median = 883 versus 619 CD4+ cells/mm(3); 41% versus 31% CD4+; CD4+/CD8+ 1.31 versus 0.77; all P< 0.0001). Finally, OVIR status was obtained in 19/35 (54%) and 7/272 (3%) patients in the PHI and CHI groups (P< 0.0001), respectively. In a logistic regression analysis, cART initiation during PHI (OR = 16, 95% CI = 3.5-72.3) and HIV DNA level <3.3 log10 before treatment (OR = 4.8, 95% CI = 1.2-19.3) were independently predictive of OVIR status. CONCLUSIONS: Initiating cART during PHI represents a major opportunity to reduce HIV reservoirs and achieve optimal immune reconstitution.

Characterization and evolution of natural aquatic biofilm communities exposed in vitro to herbicides.

River biofilms are assemblies of autotrophic and heterotrophic microorganisms that can be affected by pollutants such as those found in watersheds and wastewater treatment plants. In the laboratory, experimental biofilms were formed from river water, and their overall composition was investigated. Denaturing gradient gel electrophoresis (DGGE) and cytometry were used to assess the richness and diversity of these communities. The software Cytostack (available on request) was developed to treat and analyze the cytometric data. Measurements of chlorophyll-a and carotenoids were used to assess the global composition of the photoautotrophic community, whereas proteins, polysaccharides (PS) content, and esterase activities were used to assess overall changes in the mixed communities. We evaluated the effects that 3 weeks of treatment with the herbicides diuron and glyphosate (10 µg L(-1)) had on these biofilms. Exposed to diuron, bacterial communities adapted, changing their composition. Glyphosate inhibited growth of one autotrophic community but caused no chlorophyll deficit. As a whole, the biofilm acted as a micro-ecosystem, able to regulate and maintain a constant level of photosynthetic pigment through the structural adaptation of the autotrophic community. These results are one more proof that microbial diversity of aquatic biofilms is influenced by chemical stresses, potentially leading to disturbances within the ecosystems.

Assessment of the impact of pharmacist-led intervention with antibiotics in patients with bone and joint infection.

OBJECTIVES: The management of patients with bone and joint infections (BJIs) is complex. To improve this care, we carried out pharmaceutical actions in the orthopedic unit, including pharmacist-led-intervention (PLI) for patients requiring prolonged antibiotics. Few data exist regarding patient compliance, adherence and knowledge in cases of BJI. Data on hospital readmission are likewise limited, even though it is considered as a major determinant of clinical impact. The aim of this study was to assess the effectiveness of PLI regarding six-month readmissions. PATIENTS AND METHODS: Patients were assigned to two groups, both receiving standardized care. Two periods were compared: control group (CG) without PLI and interventional group (IG) with PLI throughout. The analysis was based on patient records and included: proportion of rehospitalizations at 6 months for infectious causes, reasons for antibiotic dose modification or antibiotic switch after 6 weeks, and descriptive analysis of data on pharmaceutical interventions in care pathways. RESULTS: Analysis was performed on 164 patients: 105 CG (64 %) patients and 59 IG (36 %) patients. There were no significant differences between IG and CG in patients' socio-demographic characteristics, infectious factors and antibiotic regimens. Amongst the CG patients, 23 were readmitted (22 %) versus 3 patients in the IG (5 %), (p = 0.002). There were significantly fewer treatment changes after 6 weeks (28.6 % versus 15.3 %, p = 0.05) for IG patients. CONCLUSION: In this retrospective survey, our results suggest a positive impact of PLI on 6-month readmission for all causes in BJI patients. These results need to be confirmed in a multicentric study.

Efficacy and Safety of Doravirine-Based Regimens in Real Life: A Prospective Monocentric French Study.

Doravirine (DOR) efficacy and safety have been evaluated in adult naive or treated patients starting a DOR-based regimen between September 15, 2019, and December 31, 2020. Medical history and examination, laboratory results, and tolerance were assessed during the 48 weeks of follow-up. Among the 77 patients included, virological control (VC) was noticed for 66 patients at baseline. Median age was 51 years, and 62% were men. The most common reason for initiating a DOR-based therapy was toxicity (44; 67%) and, especially, weight gain. A virological suppression (VS) was maintained in 55 (83%) patients of the VC group and noticed in 9 (82%) of the non-VC patients at week 48, by intention-to-treat analysis. On treatment analysis, 98% and 100% patients achieved VS in the VC and non-VC groups, respectively. The renal and metabolic tolerance were good. DOR-based regimens appear to be a safe and relevant strategy to circumvent drug interactions and drugs with a poor metabolic tolerance profile.