Objectives

To describe 7 years of experience in osteomyelitis management, from microbiological, clinical, radiological and laboratory points of view.

Material and methods: Data from clinical records from private practice in a Vascular Reference Center (Angios) located in Caracas, Venezuela; were collected retrospective, in which patients who have been diagnostic of chronic osteomyelitis and received treatment with daptomycin alone or in combination for attack phase (with curative intention); with the primary objective to evaluate microbiological and clinical outcomes and secondary endpoints as safety and efficacy. Patients evaluated among August 2009 and August 2016 were analyzed.

Result: 90 patients (68 males/22 females) with chronic osteomyelitis diagnosis were included; aged between 31 and 96 years (average 62,8 years), age over 65 years in 64 patients-71%; with comorbidities as diabetes mellitus (DM), High blood pressure (HBP) & peripheral vascular disease (PVD). The most frequently bacteria isolated in bone culture were Staphylococcus aureus (82 isolates with 76 strains resistant to methicillin and 68 strains with biofilm-positive production), coagulase- negative staphylococci (4 isolates, all methicillin-resistant & biofilm producers) and Enterococcus faecalis (4 isolates sensitive to Ampicillin and biofilm-negative production). Daptomycin was our election choice at attack phase as Outpatient Parenteral Antimicrobial Therapy (OPAT), at doses among 6 to 12mg/kg/day, alone (22 patients) or combine with Rifampicin at 600mg/PO/OD (68 patients); with mean treatment duration of 6,5 weeks (52, 5 days) (4-12 weeks). For consolidation phase, we considered 4 regimens pathogen-specific, Linezolid + Rifampicin for MRSA biofilm-positive, Moxifloxacin + Rifampicin for MSSA biofilm-positive; Moxifloxacin alone for MRS biofilm-negative and Ampicillin for Enterococcus faecalis biofilm-negative; for 4 weeks of therapy. Daptomycin resistance was absent (MICs over 1μgr/mL) and a reverse Creep MIC was observed), nor resistance develop to Linezolid, Moxifloxacin, Ampicillin or Rifampicin during treatment, and nor MIC Creep phenomenon appears. The overall treatment success rate (clinical, microbiological, radiological and laboratory values normalization) was 100% (healing). Daptomycin regimens were used in 37 patients (41,1%) as a rescue medication, and only in 21 patients as first option choice (23,3%). 16 adverse events were documented, 10 as severe fatigue and 6 CPK elevations (under 5 times NL), which not forced discontinuation of the drug in any patient (further analysis showed no causality in any case), and no reports of nephrotoxicity, pneumo, muscle-toxicity, bone narrow suppression, peripheral neuropathy or liver abnormalities were observed.

Conclusion: In Venezuelan experience, chronic osteomyelitis produced by Gram-positive cocci with high antimicrobial resistance profile and biofilm expression, the cornerstone of attack phase was Daptomycin (alone or combined with Rifampicin), follow by a consolidation therapy with slow or faster bactericidal drugs (linezolid+/-rifampicin, moxifloxacin+/-rifampicin, ampicillin), with excellent efficacy, tolerance and safety profile at the OPAT setting even in elderly patients with severe comorbidities, with a great rate of clinical, microbiological, radiological and paraclinical cure.

Keywords: Osteomyelitis; Biofilm; Daptomycin; Linezolid; Moxifloxacin; Rifampicin; Gram-positive; OPAT; Safety; Efficacy; Venezuela; Diabetic

Abstract

We retrospective describe 7 years of experience in chronic osteomyelitis management in Caracas, Venezuela, treated with daptomycin alone or in combination for attack phase and customized schemas for consolidation phase.