Low prevalence of tissue detection of cefepime and daptomycin used as empirical treatment during revision for periprosthetic joint infections: results of a prospective multicenter study.

Data demonstrating that antibiotics administered intraoperatively in patients with surgical revision for periprosthetic joint infection achieve concentrations exceeding minimal inhibitory concentrations of the identified bacteria at the surgical site when the new implant is inserted are lacking. We prospectively included patients with periprosthetic joint infection operated with one- or two-stage replacement during which cefepime (2g)-daptomycin (10mg/kg) combination was administered intravenously as intraoperative empirical antibiotic treatment. Three biopsies (two bones and one synovial membrane) were taken from each patient just before the insertion of the new implant. Eighteen adults of median age 68 years were included. Knee was involved in 10 patients (55.6%) and surgery consisted in one-/two-stage replacement in 11/7 patients. A tourniquet was used during the intervention in the 10 patients with knee prosthesis. Among 54 tissue samples, cefepime and daptomycin were detected respectively in 35 (64.8%) and 21 (38.9%) cases (P=0.01). A total of 17 bacteria dominated by staphylococci (n=14) were identified in 10 patients; tissue inhibitory quotient calculated in 51 samples was >1 in 22 cases (43.1%) for cefepime and in 16 cases (31.4%) for daptomycin. The proportion of tissue samples with detectable antibiotic was significantly higher in hip versus knee prosthesis (P=0.03). The present study suggests that intraoperative empirical administration of cefepime-daptomycin combination during septic prosthetic joint replacement results in a high proportion of tissue samples in which at least one of the two antibiotics was not detected or at a low concentration despite satisfactory concomitant blood serum concentrations.

Daptomycin versus Vancomycin as Post-Operative Empirical Antibiotic Treatment for Prosthetic Joint Infections: A Case-Control Study.

Purpose: To compare safety and efficacy of Vancomycin (Van) versus Daptomycin (Dap) as post-operative empirical antibiotic treatment (PEAT) in patients with periprosthetic joint infections (PJIs). Methods: Medical charts of patients treated empirically with Van or Dap in the post-operative period of total hip/knee prosthesis septic revision until the results of intra-operative culture were reviewed. Cefotaxime, cefepime or aztreonam were used in combination with Dap or Van. Results: Twenty Dap patients were matched with 20 other Van patients according to the age and type of prosthesis. The ASA score and the distribution of the pathogens was similar in the two groups especially regarding the number of methicillin-resistant staphylococci. The mean duration of the PEAT was 6.07 ± 0.85 days. A total of 17 episodes of adverse events (AE) in 10 patients (25%) were recorded during the PEAT which led to discontinue the treatment in 5 patients, all of them treated with Van (P=0.02). At the end of a mean post-treatment follow-up of 618 +/- 219 days, 36 patients remained in remission of infection; 2 patients failed in each group. Conclusions: Our observations suggest that PEAT with Van for septic revision of PJIs is associated with a higher discontinuation rate due to AE but with a similar outcome than it is with Dap.

Prevalence and risk factors for low bone mineral density in antiretroviral therapy-naive HIV-infected young men.

OBJECTIVE: We aimed to investigate the prevalence of low bone mineral density (BMD) and associated factors in antiretroviral therapy (ART)-naive HIV-infected young men. METHODS: In this cross-sectional study, dual-energy X-ray absorptiometry (DXA) was used to measure BMD. BMD at the lumbar spine, total hip and femoral neck sites was expressed as a Z-score (number of standard deviations away from the mean in an age, race and sex-matched reference population). Low BMD was defined as Z-scores≤-2 at any of the three sites. The prevalence of low BMD was evaluated at the lumbar spine, total hip and femoral neck sites, as were risk factors associated with Z-scores. RESULTS: The study cohort comprised 49 men, of whom 87.8% were white. Mean age was 31.6 (±7.7) years and mean BMI was 22.7 (±4.0)kg/m2. Half of patients (51.0%) were current smokers. The prevalence of low BMD was 24.5% [95% CI, 13.3-38.9]. Low estradiol levels and low BMI were associated with low Z-scores at each skeletal site, whereas current smoking and high IGF1 levels were associated with low Z-scores at the lumbar spine site. Among the HIV-related factors, low CD4+ cell count was associated with low Z-scores at the lumbar spine site. CONCLUSIONS: We observed a high prevalence of low BMD in our ART-naive cohort of young men. Risk factors associated with low Z-scores were those usually observed in HIV-infected individuals (low BMI, current smoking and CD4+ cell count) or linked to endocrine hormone levels (estradiol, IGF-1).

Suppressive antibiotic therapy with oral tetracyclines for prosthetic joint infections: a retrospective study of 78 patients.

PURPOSE: This study aimed at describing the use of oral cyclines (i.e., doxycycline and minocycline) as suppressive antibiotic therapy (SAT) in patients with periprosthetic joint infections (PJIs). METHODS: Medical charts of all patients with surgical revisions for PJIs who were given cycline-based SAT because of a high failure of various origins were reviewed. Data regarding tolerability and effectiveness of cycline-based SAT were analysed. RESULTS: Seventy-eight patients of mean age 64 ± 17 years received cycline-base SAT in the period from January 2006 to January 2014. PJIs involved the knee in 37 patients (47%), the hip in 35 (45%), the elbow in 4 (5%), and the shoulder in 2 (3%) and were qualified as early in 31 patients (39.7%). Staphylococcus spp. were the most common pathogens accounting for 72.1% of the total number of bacterial strains identified. All included patients had surgery which consisted in debridement and implant retention in 59 of them (75.6%). Doxycycline and minocycline were prescribed as SAT in 72 (92%) and 6 (8%) patients, respectively. Adverse events were reported in 14 patients (18%), leading to SAT discontinuation in 6 of them (8%). After a mean follow-up of 1020 ± 597 days, a total of 22 (28.2%) patients had failed including 3 cases (3.8%) with documented acquisition of tetracycline resistance in initial pathogen(s). CONCLUSIONS: Our results suggest that oral cyclines used as SAT in patients treated for PJI have an acceptable tolerability and effectiveness and appear to be a reasonable option in this setting.

RNA and DNA Sanger sequencing versus next-generation sequencing for HIV-1 drug resistance testing in treatment-naive patients.

Background: Sanger sequencing of plasma RNA is the standard method for HIV-1 drug resistance testing in treatment-naive patients, but is limited by the non-detection of resistance-associated mutations (RAMs) with prevalence below approximately 20%. Objectives: We compared RNA and DNA Sanger sequencing (RSS and DSS) with RNA next-generation sequencing (NGS) for RAM detection in HIV-1 reverse transcriptase (RT), protease (PR) and integrase (IN) genes. Methods: Sanger sequencing was performed on RNA and DNA, following the recommendations of the French Agency for AIDS Research (ANRS). NGS was performed on RNA using the HIV-1 Drug Resistance Assay, v. 3.0 (Roche) on the 454 GS Junior sequencer. The IAS-USA list was used to identify RAMs. ANRS, Rega and Stanford algorithms were used for drug resistance interpretation. Results: The study included 48 ART-naive patients. The number of patients with at least one major RAM was 3, 3, 4 and 8 when using RSS, DSS, NGS 20% and NGS 5%, respectively. Numerous minor mutations were detected in patients, especially in the protease gene. None of the methods detected any major mutation in the integrase gene. Overall, the mutation detection rate was similar between RSS and DSS, and higher with NGS 20%. Differences in drug resistance interpretation were found between algorithms. No impact of the minority RAMs detected by NGS was found on the short-term treatment outcome. Conclusions: DSS does not clearly improve the detection of RAMs in ART-naive patients, as compared with RSS. NGS allows detection of additional minority RAMs; however, their clinical relevance requires further investigation.

Suppressive antibiotic therapy with oral doxycycline for Staphylococcus aureus prosthetic joint infection: a retrospective study of 39 patients.

The aim of this study was to describe the use of oral doxycycline as suppressive antibiotic therapy (SAT) in patients with Staphylococcus aureus periprosthetic (hip or knee) joint infections. The medical charts of all patients with surgical revisions for S. aureus hip or knee prosthetic joint infections (PJIs) who were given doxycycline-based SAT because of a high risk of failure of various origins were reviewed. Data regarding tolerability and effectiveness of doxycycline-based SAT were analysed. A total of 39 patients (mean age 66.1 ± 16.3 years) received doxycycline-base SAT in the period from January 2006 to January 2014. PJIs involved the hip in 23 patients (59.0%) and the knee in 16 (41.0%), and were qualified as early in 15 patients (38.5%). Methicillin-resistant S. aureus (MRSA) accounted for 22% of the total number of bacterial strains identified. All patients included in the study had surgery, which consisted of debridement and implant retention in 32 (82.1%). Adverse events likely attributable to SAT were reported in six patients (15.4%), leading to discontinuation of SAT in three (7.7%). A total of 29 patients (74.4%) remained event-free and 10 (25.6%) failed, including 8 (20.5%) relapses and 2 (5.1%) superinfections. Overall, 8 of the 10 failure cases were related to a doxycycline-susceptible pathogen. These results suggest that oral doxycycline used as SAT in patients treated for S. aureus hip or knee PJIs has an acceptable tolerability and effectiveness and appears to be a reasonable option in this setting.

Counter-intuitive plasma vitamin D and zinc status in HIV-1-infected adults with persistent low-level viraemia after treatment initiation: a pilot case-control study.

Determinants of persistent low-level viraemia [PLLV, a viral load (VL) of between 50 and 500 copies/mL] have not been elucidated. In a case-control study, we evaluated the influence of micronutrients on PLLV in a population of 454 HIV-1 adults having initiated antiretroviral therapy (ART) between January 2007 and December 2011. Plasma levels of retinol (vitamin A), 25-OH vitamin D2 + D3, vitamin E and zinc were measured at ART initiation in cases (PLLV after 6 months of ART) and in controls (VL <50 copies/mL after 6 months). Cases and controls were matched for the CD4 cell count (±50/mm3) and ethnic origin. Intergroup differences in demographic, biological and treatment parameters and sunshine intensity at ART initiation were adjusted using a propensity score. A receiver operating characteristic (ROC) curve was used to assess intergroup differences in plasma micronutrient levels. Thirty-three of the 454 patients (7.3%) displayed PLLV (median VL: 92 copies/mL). Patients were predominantly male (89%), Caucasian (64%) and CDC stage C (25%). The median age was 38 years, the median initial VL was 5.2 log10 copies/mL and the median CD4 count was 74/mm3. The 22 cases and matched controls were balanced in these respects, and had similar vitamin A/E levels. Two cases (9%) and 9 controls (41%) had a vitamin D level <10.3 ng/mL (p = 0.0015), and 2 cases (9%) and 10 controls (48%) had a zinc level <74.6 µg/dL (p = 0.04). Our results support in vitro studies suggesting that vitamin D favours HIV-1 replication and that HIV-1 is zinc-dependent. Wide-scale, prospective studies are required.

Outcome of patients with streptococcal prosthetic joint infections with special reference to rifampicin combinations.

BACKGROUND: Outcome of patients with streptococcal prosthetic joint infections (PJIs) is not well known. METHODS: We performed a retrospective multicenter cohort study that involved patients with total hip/knee prosthetic joint (THP/TKP) infections due to Streptococcus spp. from 2001 through 2009. RESULTS: Ninety-five streptococcal PJI episodes (50 THP and 45 TKP) in 87 patients of mean age 69.1 ± 13.7 years met the inclusion criteria. In all, 55 out of 95 cases (57.9 %) were treated with debridement and retention of the infected implants with antibiotic therapy (DAIR). Rifampicin-combinations, including with levofloxacin, were used in 52 (54.7 %) and 28 (29.5 %) cases, respectively. After a mean follow-up period of 895 days (IQR: 395-1649), the remission rate was 70.5 % (67/95). Patients with PJIs due to S. agalactiae failed in the same proportion as in the other patients (10/37 (27.1 %) versus 19/58 (32.7 %); p = .55). In the univariate analysis, antibiotic monotherapy, DAIR, antibiotic treatments other than rifampicin-combinations, and TKP were all associated with a worse outcome. The only independent variable significantly associated with the patients' outcomes was the location of the prosthesis (i.e., hip versus knee) (OR = 0.19; 95 % CI 0.04-0.93; p value 0.04). CONCLUSIONS: The prognosis of streptococcal PJIs may not be as good as previously reported, especially for patients with an infected total knee arthroplasty. Rifampicin combinations, especially with levofloxacin, appear to be suitable antibiotic regimens for these patients.

Optimising the quality and outcomes of treatments for diabetic foot infections.

INTRODUCTION: Infection is the commonest foot complication that arises in people with diabetes and may lead to amputation and even death. The emergence of multidrug resistant bacteria, especially in Gram negative rods, may have a negative impact on the chances of cure in these patients. AREAS COVERED: We searched the Medline and Pubmed databases for studies using the keywords 'diabetic foot infection' and 'diabetic foot osteomyelits' from 1980 to 2016. Expert commentary: Much has been done in the field of diabetic foot infection regarding pathophysiology, diagnosis and treatment. The construction of multidisciplinary teams is probably the most efficient way to improve the patients' outcome. The rational use of antibiotics and surgical skills are essential in these potentially severe infections. Each case of diabetic infection deserves to be discussed in the light of the current guidelines and the local resources. Because of the overal poor outcome of these infections, prevention remains a priority.

Influence of daily dosage and frequency of administration of rifampicin-levofloxacin therapy on tolerance and effectiveness in 154 patients treated for prosthetic joint infections.

Data on the tolerance and effectiveness of rifampicin-levofloxacin combination therapy (RLCT) in patients treated for prosthetic joint infections (PJIs) according to daily dosage are lacking. A review of the clinical data from patients treated with RLCT for PJIs in a French referent center for PJIs was conducted. A total of 154 patients (75 F/79 M), with a median age of 64.1 years and median body weight of 83.1 kg, were included. The median daily dosages of rifampicin and levofloxacin were, respectively, 1,200 mg (range 300-2,100) and 750 mg (range 500-1,500), corresponding to a mean daily dose per kg of, respectively, 16.2 ± 4.3 mg/kg and 10.1 ± 3.0 mg/kg. After a mean follow-up period of 55.6 ± 27.1 months (range 24-236), 127 patients (82.5 %) were in remission. Adverse events attributable to rifampicin and levofloxacin were reported in 48 (31.2 %) and 13 (8.4 %) patients (p < 0.001), respectively. Patients who experienced rifampicin-related adverse events had been given higher rifampicin daily doses than the other patients (p = 0.04). The rifampicin daily dosage did not influence patient outcome and nor did the levofloxacin daily dosage on both tolerance and patient outcome. Our results suggest that adjusting rifampicin daily doses to the patient total body weight when combined with levofloxacin for the treatment of PJIs is associated with a poor tolerance. High daily doses of rifampicin (>600 mg) and levofloxacin (750 mg) do not improve patient outcome when compared to lower daily doses in this setting.