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.).

Daptomycin > 6 mg/kg/day as salvage therapy in patients with complex bone and joint infection: cohort study in a regional reference center.

BACKGROUND: Even if daptomycin does not have approval for the treatment of bone and joint infections (BJI), the Infectious Diseases Society of America guidelines propose this antibiotic as alternative therapy for prosthetic joint infection. The recommended dose is 6 mg/kg/d, whereas recent data support the use of higher doses in these patients. METHODS: We performed a cohort study including consecutive patients that have received daptomycin >6 mg/kg/d for complex BJI between 2011 and 2013 in a French regional reference center. Factors associated with treatment failure were determined on univariate Cox analysis and Kaplan-Meier curves. RESULTS: Forty-three patients (age, 61 ± 17 years) received a mean dose of 8 ± 0.9 mg/kg/d daptomycin, for a mean 81 ± 59 days (range, 6-303 days). Most had chronic (n = 37, 86 %) implant-associated (n = 37, 86 %) BJI caused by coagulase-negative staphylococci (n = 32, 74 %). A severe adverse event (SAE) occurred in 6 patients (14 %), including 2 cases of eosinophilic pneumonia, concomitant with daptomycin Cmin >24 mg/L. Outcome was favorable in 30 (77 %) of the 39 clinically assessable patients. Predictors for treatment failure were age, non-optimal surgery and daptomycin withdrawal for SAE. CONCLUSIONS: Prolonged high-dose daptomycin therapy was effective in patients with complex BJI. However, optimal surgery remains the cornerstone of medico-surgical strategy; and a higher incidence of eosinophilic pneumonia than expected was recorded.

Acyclovir treatment of varicella-zoster virus meningeal infections and acute kidney injury: a multicentre case series study.

BACKGROUND: Systematic treatment with intravenous acyclovir is usually given when varicella zoster virus (VZV) DNA is isolated in cerebrospinal fluid (CSF), indicating central nervous system (CNS) involvement. Our study aimed to describe therapeutic management and acute kidney injury (AKI) occurrence during acyclovir treatment of VZV infection with CNS involvement. METHODS: Multicentre, retrospective study including all patients from 2010 to 2022 with VZV DNA in CSF. Patient management and outcomes were compared according to clinical presentation and indications for intravenous acyclovir: i) definite (encephalitis, myelitis or stroke, peripheral nervous system (PNS) with ≥ 2 roots, herpes zoster ≥ 3 dermatomes, immunosuppression), ii) questionable (1 or 2 dermatomes) or iii) no indication (other situations). RESULTS: 154 patients were included (median age 66 (interquartile range 43-77), 87 (56%) males); 60 (39%) had encephalitis, myelitis or stroke, 35 (23%) had PNS involvement, 37 (24%) had isolated meningitis, 14 (9%) had isolated cutaneous presentation, and 8 (5%) had other presentations. Overall, 128 (83%) received intravenous acyclovir for more than 72 h. AKI occurred in 57 (37%) patients. Finally, 42 (27%) and 25 (16%) patients had respectively no or a questionable indication for intravenous acyclovir, while 29 (69%) and 23 (92%) of them received it for more than 72 h, with AKI in 13 (35%) and 13 (52%) patients, respectively. In-hospital mortality was 12% (n = 18), and no deaths were reported in isolated meningitis. CONCLUSIONS: Intravenous acyclovir is widely prescribed when VZV DNA is isolated in CSF, regardless of the clinical presentation, with a high rate of AKI. Further studies are needed to better define the value of intravenous acyclovir in isolated VZV meningitis.

In vivo efficacy of humanised intermittent versus continuous ceftazidime in combination with tobramycin in an experimental model of pseudomonal pneumonia.

In this study, we compared the efficacy of ceftazidime (CAZ) intermittent versus continuous infusion with or without tobramycin (TOB) for the treatment of pneumonia caused by Pseudomonas aeruginosa in rabbits. Treatments were humanised and mimicked intermittent CAZ (iCAZ) (2g three times daily), continuous CAZ (cCAZ) (4g once daily (qd)) and TOB (10mg/kg qd). Minimum inhibitory concentrations (MICs) were 1mg/L and 4mg/L for TOB and CAZ, respectively. Bacterial efficacy in lungs was as follows: control, 9+/-0.6 colony-forming units (CFU)/g; TOB monotherapy, 8+/-0.5CFU/g; iCAZ monotherapy, 7.8+/-1.4CFU/g; cCAZ monotherapy, 8+/-0.4CFU/g (P = 0.005); and iCAZ+TOB, 8+/-0.5CFU/g; cCAZ+TOB, 7.2+/-0.3CFU/g (P < 0.05). Bacterial efficacy in the spleen was as follows (% sterile): control, 4+/-1.6CFU/g (0%); TOB monotherapy, 1.7+/-1.2CFU/g (60%); iCAZ monotherapy, 3.5+/-0.5CFU/g (17%); cCAZ monotherapy, 1.5+/-0.6CFU/g (75%) (P = 0.02); and iCAZ+TOB, 2.1+/-0.6CFU/g (50%); cCAZ+TOB, 1.2+/-0.3CFU/g (82%) (P < 0.05). The time the drug concentration was above the MIC (T > MIC) was 62% and 99% for iCAZ and cCAZ, respectively. We conclude that CAZ is more effective when administered continuously, especially for the sterilisation of septicaemia. A synergistic therapeutic effect of the association CAZ+TOB was observed in vivo, which can be explained by the longer T > MIC of cCAZ. These findings suggest that continuous treatment with 4g CAZ could be appropriate in patients with P. aeruginosa infections.

[Capnocytophaga canimorsus: atypical septicemic meningitis, approach to microbiological diagnosis and therapeutic impact]. / Capnocytophaga canimorsus : méningite septicémique atypique, démarche du diagnostic microbiologique et impact thérapeutique.

Meningitis and septicaemia due to Capnocytophaga canimorsus are extremely rare and described as emerging zoonoses because of their low incidence and prevalence, but also because of the challenges in bacterial identification, thus, the real number of cases is probably underestimated. We report the case of a 61-year-old man, with a history a chronic alcoholism, who developed, following a recent dog bite, meningitis with normoglycorachia and concomitant sepsis, and had a favorable outcome after intravenous probabilistic antibiotherapy combining ceftazidime and metronidazole. This association aimed to cover the risks represented by Pseudomonas spp and anaerobic bacteria, once the microorganisms commonly associated with meningitis were excluded using molecular biology tools. In addition to the unusual biological results (normoglycorachia and bacterial morphology after Gram staining), we present the biological diagnostic approach (molecular, biochemical and physical tools successively used to lead, by exclusion and confirmation, to this diagnosis), closely linked to the clinical expertise. This is, to our knowledge, the first described case of meningitis with normoglycorachia and septicaemia due to Capnocytophaga canimorsus successfully treated with ceftazidime and confirmed by identification by MALDI-TOF mass spectrometry.

Epidemiology, diagnosis and treatment of chronic hepatitis B in HIV-infected patients (EPIB 2005 STUDY).

OBJECTIVE: To describe the characteristics of hepatitis B (HBV) infection in HIV-infected patients and the impact of anti-HBV treatments. PATIENTS AND METHODS: All the patients with past or present chronic HBV infection seen in October 2005 in 17 French hospitals were included. Data were retrospectively collected from their first visit in a time-dependent manner, through a detailed standardized questionnaire. RESULTS: Among 477 HBV-infected patients, 261 (55%) were co-infected with HIV. The HBV-HIV co-infected patients underwent fewer serological, virological and histological evaluations. Initial positive HBe antigenemia (HBe Ag) was more frequent in these patients (57.9 versus 28.6%; P < 10), as was cirrhosis on the initial liver biopsy (17.9 versus 7.6%; P = 0.05). Throughout the mean 5-year follow-up, HBe Ag loss was less frequent (P = 0.04), as was HBe seroconversion (incidence rate 2.6 versus 10/100 patient-years; P < 10). HBe Ag loss was associated with fibrosis improvement (METAVIR score -0.5 +/- 0.4 versus +0.2 +/- 0.6 if persistent positive HBe Ag, P = 0.01). In co-infected patients on tenofovir, adefovir or interferon, HBe seroconversions were seen in patients on combined HBV treatment, the use of which is increasing (58% in 2005). Nevertheless, no significant difference in virological, immunological or biochemical evolution was observed between these different treatments. CONCLUSIONS: In HBV-HIV co-infected patients, the assessment of HBV infection still needs to be improved, the HBV wild-type remains predominant, and HBe Ag loss is rare and associated with a better histological evolution. There is insufficient evidence of the superiority of combined HBV treatment, and this still needs be demonstrated in long term studies.

Concentration of circulating oxidized LDL in HIV-infected patients treated with antiretroviral agents: relation to HIV-related lipodystrophy.

BACKGROUND: Circulating oxidized LDL (ox-LDL) is associated with clinical manifestations of atherosclerosis. The aim of the study was to investigate the concentrations of ox-LDL in HIV-infected patients under antiretroviral therapy with (HIV-LD) or without (HIV-nLD) HIV-related lipodystrophy. METHOD: A total of 44 HIV-infected men were enrolled in the study. Half of them had HIV-LD. The control group included 12 age- and body mass index (BMI)-matched HIV-uninfected men. Ox-LDL concentration and C-reactive protein level were determined. Insulin sensitivity was measured using the homeostasis model assessment (HOMA-IR). LD was assessed by using a validated score calculated from clinical and biological data. RESULTS: HIV-infected patients had significantly higher ox-LDL concentrations when compared to HIV-negative controls (0.8 +/- 0.3 mg/dL vs. 0.60 +/- 0.1 mg/dL; p = .007). HIV-LD patients had significantly higher ox-LDL concentrations than HIV-nLD patients (0.91 +/- 0.38 and 0.69 +/- 0.16; p = .04). In HIV-LD patients, current therapy with protease inhibitors (PIs); duration of PI therapy; HOMA-IR; and time exposure to stavudine, efavirenz, ritonavir, saquinavir, and amprenavir were significantly higher than in HIV-nLD patients. In multivariate analysis, time exposures to stavudine and ox-LDL concentration were independently related to lipodystrophy. CONCLUSION: The high concentration of ox-LDL was found in HIV-infected patients under antiretroviral therapy, especially in those with lipodystrophy.

[Acute Gemella haemolysans spondylodiscitis in an immunocompetent patient]. / Spondylodiscite aiguë à Gemella haemolysans chez une patiente immunocompétente.

INTRODUCTION: Gemella is a commensal bacterium of the upper respiratory tract responsible for rare infections such as acute endocarditis and meningitis. We report the case of an acute Gemella haemolysans spondylodiscitis. OBSERVATION: A 72 year-old woman was hospitalised for an etiological control and treatment of acute L4-L5 spondylodiscitis with epiduritis, confirmed on MRI. The clinical picture was composed of backache with shivering and alteration in general status of health. The peripheral bacteriological samples, intra-dermal reaction and brucella serology were all negative. The surgical L5 biopsy, following bacteriological enrichment, isolated Gram-positive cocci, later identified as Gemella haemolysans. The antibiogram showed good sensitivity to amoxicillin, dalacin and erythromycin, and strong resistance to aminosides. The search for a contamination point was negative. The patient rapidly improved with antibiotics combining 6 g/d of amoxicillin and 1200 mg/d of clindamycin, and the biological and clinical signs regressed. The antibiotic bi-therapy was continued for two and a half months and then relayed to amoxicillin alone for two further weeks. COMMENTS: The first descriptions of Gemella haemolysans infection were made in the seventies. Cases of infectious endocarditis were succeeded by septicaemia on cirrhosis and later a few cases of acute post-neurosurgical meningitis. In the majority of cases, a dental contamination point was found. The difficulties in its etiological diagnosis, related to the problems in identifying this germ that has similar characteristics to Streptococcus viridans, suggests that the prevalence of Gemella haemolysans infections is greatly underrated. The sensitivity profile generally observed is sensitivity to penicillins and aminosides--the association of which is synergic--, to cyclines and glycopeptides, and resistance to trimethoprime-sulfamethoxazole.

Treatment of chronic hepatitis C in HIV-infected patients: from clinical trials to field practice.

In a prospective cohort of 87 HIV coinfected patients with chronic hepatitis C, 63% had been treated for HCV, with global success rate (47%, 95% CI 34-61) close to or higher than that reported in therapeutic trials. These results argue for earlier, more frequent and improved HCV treatment in HIV-infected patients.

Prevalence and impact of GBV-C, SEN-V and HBV occult infections in HIV-HCV co-infected patients on HCV therapy.

BACKGROUND/AIMS: It has been suggested that, in HIV-HCV co-infected patients, co-infections with other viruses may affect the response to HCV therapy. We aimed to assess the prevalence of GBV-C, SEN-V and occult HBV infections, their impact on HCV and HIV infections and on the response to HCV therapy in HIV-HCV co-infected patients. METHODS: Three-hundred and sixty eight patients were tested before starting interferon-ribavirin for the presence of occult hepatitis B DNA, GBV-C RNA and SEN-V DNA by using real time PCR. Clinical, immunological, virological, histological characteristics and response to HCV therapy were compared according to the presence or not of each viral co-infection. RESULTS: HBV DNA, GBV-C RNA and SEN-V DNA were found in 5 (1.4%, CI95%: 0.2-2.4%), 104 (29.9%, CI95%: 25.1-34.7%) and 209 patients (57.9%, CI95%: 52.8-63.0%), respectively. GBV-C positive patients had significantly higher CD4 count at baseline, during and after HCV therapy, even after stratification on antiretroviral treatment. No other significant difference was observed according to the presence or not of GBV-C or SEN-V co-infection, in particular regarding virological responses to HCV combination therapy. CONCLUSIONS: There is no reason to withhold HCV therapy in HIV infected patients who have access to HAART, because of occult HBV, GBV-C or SEN-V co-infections.

Low trough plasma concentrations of nevirapine associated with virologic rebounds in HIV-infected patients who switched from protease inhibitors.

BACKGROUND: The substitution of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) for protease inhibitors (PIs) has demonstrated its suitability to maintain virologic response. However, the switch from PIs to an NNRTI could fail for a number of reasons, including NNRTI-associated toxicity and emergence of NNRTI-resistant variants. OBJECTIVE: To describe the virologic failures among 74 HIV-infected patients who switched from PIs to nevirapine. METHODS: Virologic failure was defined as any rebound of the plasma HIV-RNA (pVL) levels >1000 copies/mL on one occasion or 2 consecutive intermittent viremia episodes defined as increases of the pVL >20 copies/mL but <1000 copies/mL. Virologic failures were investigated retrospectively by determining nevirapine trough concentrations and performing genotypic resistance analysis. RESULTS: The mean nevirapine concentration was significantly lower in patients with virologic failure in comparison with patients with virologic response (2572 +/- 1642 vs 4550 +/- 2084 ng/mL, respectively; p = 0.003). In multivariate analysis, the mean duration of undetectable pVL before the switch and the mean plasma concentration of nevirapine were significantly associated with virologic success with relative rates of 1.39 (95% CI 1.10 to 1.76, p = 0.006) and 2.7 (95% CI 1.37 to 5.41, p = 0.01), respectively. In patients with pVL >1000 copies/mL, nevirapine mutations and nucleoside reverse-transcriptase inhibitor mutations were found in 80% of the cases. CONCLUSIONS: The risk of virologic failure after the switch from PI to nevirapine is higher in cases of inadequate nevirapine plasma concentrations. Our data support prospective monitoring of nevirapine plasma concentrations to detect low concentrations prior to the emergence of resistance mutations.