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.

Antibiotic Stewardship in Treatment of Osteoarticular Infections Based on Local Epidemiology and Bacterial Growth Times.

Incubation for 14 days is recommended for the culture of microorganisms from osteoarticular infections (OAI), but there are no recommendations for postoperative antibiotic stewardship concerning empirical antimicrobial therapy (EAT), while prolonging broad-spectrum EAT results in adverse effects. The aim of this study was to describe the local OAI epidemiology with consideration of bacterial growth times to determine which antibiotic stewardship intervention should be implemented in cases of negative culture after 2 days of incubation. We performed a 1-year, single-center, noninterventional cohort study at the Pitié-Salpêtrière hospital OAI reference center. Samples were taken as part of the local standard of care protocol for adult patients who underwent surgery for OAI (native or device related) and received EAT (i.e., piperacillin-tazobactam plus daptomycin [PTD]) following surgery. The time to culture positivity was monitored daily. Overall, 147 patients were recruited, accounting for 151 episodes of OAI, including 112 device-related infections. Microbiological cultures were positive in 144 cases, including 42% polymicrobial infections. Overall, a definitive microbiological result was obtained within 48 h in 118 cases (78%) and within 5 days in 130 cases (86%). After 5 days, only Gram-positive bacteria were recovered, especially Cutibacterium acnes, Staphylococcus spp., and Streptococcus spp. Overall, 90% of culture-positive OAI were correctly treated with the locally established EAT. EAT guidance for OAI was in agreement with our local epidemiology. Our results supported antibiotic stewardship intervention consisting of stopping piperacillin-tazobactam treatment at day 5 in cases of negative culture. IMPORTANCE Osteoarticular infections (OAI) remain challenging to diagnose and to treat. One of the issues concerns postoperative empirical antimicrobial therapy (EAT), which is usually a combination of broad-spectrum antibiotics. This EAT is maintained up to 2 weeks, until the availability of the microbiological results (identification and drug susceptibility testing of the microorganisms responsible for the OAI). Our results provide new data that will help to improve OAI management, especially EAT. Indeed, we have shown that antibiotic stewardship intervention consisting of stopping the antibiotic targeting Gram-negative bacteria included in the EAT could be implemented in cases where culture is negative after 5 days of incubation. The benefits of such an antibiotic stewardship plan include improved patient outcomes, reduced adverse events (including Clostridioides difficile infection), improvement in rates of susceptibilities to targeted antibiotics, and optimization of resource utilization across the continuum of care.

Clinical Features and Outcome of Multidrug-Resistant Osteoarticular Tuberculosis: A 12-Year Case Series from France.

The optimal treatment for osteoarticular infection due to multidrug-resistant tuberculosis strains (MDR-OATB) remains unclear. This study aims to evaluate the diagnosis, management and outcome of MDR-OATB in France. We present a case series of MDR-OATB patients reviewed at the French National Reference Center for Mycobacteria between 2007 and 2018. Medical history and clinical, microbiological, treatment and outcome data were collected. Twenty-three MDR-OATB cases were reported, representing 3% of all concurrent MDR-TB cases in France. Overall, 17 were male, and the median age was 32 years. Six patients were previously treated for TB, including four with first-line drugs. The most frequently affected site was the spine (n = 16). Bone and joint surgery were required in 12 patients. Twenty-one patients (91%) successfully completed the treatment with a regimen containing a mean of four drugs (range, 2-6) for a mean duration of 20 months (range, 13-27). Overall, high rates of treatment success were achieved following WHO MDR-TB treatment guidelines and individualized patient management recommendations by the French National TB Consilium. However, the optimal combination of drugs, duration of treatment and role of surgery in the management of MDR-OATB remains to be determined.

A case of tuberculosis and black-grain eumycetoma co-infection in a non-endemic country: clinical presentation and therapeutic management.

We report a case of black-grain eumycetoma co-localized with Mycobacterium tuberculosis infection, presenting as a painless leg abscess and associated with vertebral tuberculosis. The rare association of these two pathogens raises several challenges regarding foreseeable drug interactions, side effects, the most appropriate management, and the potential link between these two diseases.

Ciprofloxacin population pharmacokinetics during long-term treatment of osteoarticular infections.

BACKGROUND: Ciprofloxacin is an antibiotic used in osteoarticular infections owing to its very good bone penetration. Very few pharmacokinetic data are available in this population. OBJECTIVES: To investigate oral ciprofloxacin population pharmacokinetics in adult patients treated for osteoarticular infections and propose guidance for more effective dosing. METHODS: A retrospective population-pharmacokinetic analysis was performed on 92 consecutive hospitalized patients in the orthopaedic department. Ciprofloxacin plasma samples were obtained on one or two occasions during treatment. Plasma concentration was measured using ultra-performance liquid chromatography system coupled with tandem mass spectrometry. Data analysis was performed using a non-linear mixed-effect approach via Monolix 2019R2. RESULTS: A total of 397 plasma samples were obtained with 11.5% and 41.6% of patients being below the therapeutic target for Gram-negative and staphylococcal infections, respectively. Ciprofloxacin pharmacokinetics were best described by a two-compartment model with a first-order absorption. Ciprofloxacin apparent plasma clearances and volumes of distribution were dependent on patients' fat-free mass according to the allometric rule. Elimination clearance was also positively related to renal function through the modification of diet in renal disease equation (MDRD) and rifampicin co-administration. When patients are co-treated with rifampicin, ciprofloxacin dosage should be increased by 50% to 60%. CONCLUSIONS: This study showed that free-fat mass was a better size predictor than total body weight for ciprofloxacin clearance and volumes terms. Moreover, both MDRD and rifampicin status were significant predictors of individual ciprofloxacin clearance. Our study suggests that individual adjustment of ciprofloxacin dose in osteoarticular infections with less-susceptible bacteria might be indicated to reach required efficacy targets.

Diabetic foot ulcer management in a multidisciplinary foot centre: one-year healing, amputation and mortality rate.

OBJECTIVE: To describe the rates of healing, major amputation and mortality after 12 months in patients with a new diabetic foot ulcer (DFU) and their care in a French diabetic foot service (DFS). METHOD: A prospective single-centre study including patients from March 2009 to December 2010. The length of time to healing, minor amputation, major amputation and mortality rate after inclusion were analysed using the Kaplan-Meier method. RESULTS: Some 347 patients were included (3% lost to follow-up), with a median follow-up (IQR) of 19 (12-24) months. The mean (SD) age was 65±12 years, 68% were male, and the median duration of the ulcer was 49 (19-120) days. Complications of the DFU were ischaemia (70%), infection (55%) and osteomyelitis (47%). Of the patients, 50% were inpatients in the DFS at inclusion (median duration of hospitalisation 26 (15-41) days). The rate of healing at one year was 67% (95% confidence interval (CI): 61-72); of major amputation 10% (95% CI: 7-17); of minor amputation 19% (95% CI: 14-25), and the death rate was 9% (95% CI: 7-13). Using an adjusted hazard ratio, the predictive factors of healing were perfusion and the area of the wound. The risk factors for a major amputation were active smoking and osteomyelitis. The risk factors for mortality were perfusion and age. CONCLUSION: This study confirms the need to treat DFUs rapidly, in a multidisciplinary DFS.

Diabetic foot ulcer management in a multidisciplinary foot centre: one-year healing, amputation and mortality rate.

OBJECTIVE: To describe the rates of healing, major amputation and mortality after 12 months in patients with a new diabetic foot ulcer (DFU) and their care in a French diabetic foot service (DFS). METHOD: A prospective single-centre study including patients from March 2009 to December 2010. The length of time to healing, minor amputation, major amputation and mortality rate after inclusion were analysed using the Kaplan-Meier method. RESULTS: Some 347 patients were included (3% lost to follow-up), with a median follow-up (IQR) of 19 (12-24) months. The mean (SD) age was 65±12 years, 68% were male, and the median duration of the ulcer was 49 (19-120) days. Complications of the DFU were ischaemia (70%), infection (55%) and osteomyelitis (47%). Of the patients, 50% were inpatients in the DFS at inclusion (median duration of hospitalisation 26 (15-41) days). The rate of healing at one year was 67% (95% confidence interval (CI): 61-72); of major amputation 10% (95% CI: 7-17); of minor amputation 19% (95% CI: 14-25), and the death rate was 9% (95% CI: 7-13). Using an adjusted hazard ratio, the predictive factors of healing were perfusion and the area of the wound. The risk factors for a major amputation were active smoking and osteomyelitis. The risk factors for mortality were perfusion and age. CONCLUSION: This study confirms the need to treat DFUs rapidly, in a multidisciplinary DFS.

Development and validation of a UPLC-MS/MS method for simultaneous quantification of levofloxacin, ciprofloxacin, moxifloxacin and rifampicin in human plasma: Application to the therapeutic drug monitoring in osteoarticular infections.

BACKGROUND: Fluoroquinolones and rifampicin are antibiotics frequently used for the treatment of osteoarticular infections, and their therapeutic drug monitoring is recommended. The aim of this study was to develop and validate a rapid and selective method of simultaneous quantification of levofloxacin, ciprofloxacin, moxifloxacin and rifampicin with short pretreatment and run times in order to be easily used in clinical practice. METHODS: After a simple protein precipitation of plasma samples, the chromatographic separation was performed using an ultra-performance liquid chromatography system coupled with mass tandem spectrometry in a positive ionization mode. The mobile phase consisted of a gradient elution of water-formic acid (100:0.1, v/v)-ammonium acetate 2 mM (A) and methanol-formic acid (100:0.1, v/v)-ammonium acetate 2 mM (B) at a flow rate at 0.3 mL/min. RESULTS: Analysis time was 5 min per run, and all analytes and internal standards eluted within 0.85-1.69 minutes. The calibration curves were linear over the range from 0.5-30 µg/mL for levofloxacin, ciprofloxacin, moxifloxacin and rifampicin with linear regression coefficients above 0.995 for all analytes. The intra-day and inter-day coefficients of variation were below 10 % for lower and higher concentration. This method was successfully applied to drug monitoring in patients with an osteoarticular infection. CONCLUSION: A simple, rapid, and selective liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of levofloxacin, ciprofloxacin, moxifloxacin and rifampicin in human plasma.

[Surgical management of diabetic foot osteomyelitis]. / Prise en charge chirurgicale de l'ostéite du pied chez le diabétique.

SURGICAL MANAGEMENT OF DIABETIC FOOT OSTEOMYELITIS. painless due to diabetic neuropathy. Osteomyelitis is most often managed surgically after both clinico-radiological examination of the wound and treatment of an arteriopathy if present. Multiple conservative surgical techniques currently exist, depending on the infection's location, and aim to treat and prevent ulcer recurrence. These techniques are briefly described presently. Combined conservative surgery, appropriate antibiotherapy, and off-loading allow full healing in the majority of cases. Amputation should only be considered after failure of conservative treatment or in the presence of severe vascular lesions or untreatable arteriopathy.

PRISE EN CHARGE CHIRURGICALE DE L'OSTÉITE DU PIED CHEZ LE DIABÉTIQUE. L'ostéite est une complication fréquente et grave des plaies du pied chez le diabétique. Il s'agit d'une infection de contiguïté liée à l'indolence de la plaie du fait de la neuropathie diabétique. La prise en charge de ces ostéites est le plus souvent chirurgicale après un bilan clinique et radiologique de la plaie et la recherche d'une artériopathie associée qui nécessite une prise en charge première. De nombreuses techniques chirurgicales conservatrices en fonction du bilan préopératoire et de la localisation de l'ostéite sont utilisables actuellement afin de traiter cette infection et de prévenir les récidives. Ses différentes techniques sont succinctement décrites. La chirurgie associée à une antibiothérapie adaptée et à une décharge stricte de la plaie permet la guérison dans la grande majorité des cas. L'amputation ne doit être envisagée qu'après échec du traitement conservateur ou lors de lésions vasculaires graves avec artériopathie sévère associée non traitable.

Erwinia billingiae as Unusual Cause of Septic Arthritis, France, 2017.

In 2017 in France, we treated a patient with knee septic arthritis caused by Erwinia billingiae after trauma involving a palm tree. This rare pathogen could only be identified through 16S rRNA gene sequencing. For bacterial infections after injuries with plants, 16S rRNA gene sequencing might be required for species identification.