Streptogramins for the treatment of infections caused by Gram-positive pathogens.

INTRODUCTION: Streptogramins (pristinamycin and quinupristin-dalfopristin) can be interesting options for the treatment of infections due to Gram-positive cocci, especially multidrug-resistant isolates. AREAS COVERED: This review provides an updated overview of structural and activity characteristics, mechanisms of action and resistance, pharmacokinetic/pharmacodynamic, and clinical use of streptogramins. EXPERT OPINION: The streptogramin antibiotics act by inhibition of the bacterial protein synthesis. They are composed of two chemically distinct compounds, namely type A and type B streptogramins, which exert a rapid bactericidal activity against a wide range of Gram-positive bacteria (including methicillin-resistant staphylococci and vancomycin-resistant enterococci). Several mechanisms of resistance have been identified in staphylococci and enterococci but the prevalence of streptogramin resistance among clinical isolates remains very low. Even if only a few randomized clinical trials have been conducted, the efficacy of pristinamycin has been largely demonstrated with an extensive use for 50 years in France and some African countries. Despite its effectiveness in the treatment of severe Gram-positive bacterial infections demonstrated in several studies and the low rate of reported resistance, the clinical use of quinupristin-dalfopristin has remained limited, mainly due to its poor tolerance. Altogether, streptogramins (especially pristinamycin) can be considered as potential alternatives for the treatment of Gram-positive infections.

[Ulcerations of the extremities: An unusual manifestation of Behçet's disease]. / Ulcérations des extrémités : une manifestation inhabituelle de la maladie de Behçet.

BACKGROUND: Although cutaneous and mucosal involvement is a major manifestation in Behçet's disease, ulcerated lesions of the extremities are exceptional and poorly known. CASE REPORT: A 57-year-old male patient was diagnosed 7 years ago with Behçet's disease. This diagnosis was made in the presence of recurrent bipolar aphtous ulcers, pseudofolliculitis lesions and retinal vasculitis. After having been lost to follow up for two years, during which his treatment was discontinued, he presented centimetric necrotic ulcerations of the fingers of the hand and of the right big toe. The biopsy revealed leucocytoclastic and necrotizing vasculitis. The patient improved with antibiotic, oral corticosteroids, colchicine and local care. CONCLUSION: Linking extremity ulcers with Behçet's disease, though sometimes difficult, is essential for proper management.

Oral pristinamycin for the treatment of resistant Gram-positive infections in patients with cancer: Evaluation of clinical outcomes.

Pristinamycin has been used to treat a range of Gram-positive infections, but reported experience in patients with malignancy is limited. This study aimed to evaluate the use of pristinamycin in patients with cancer at an Australian centre. All patients commenced on oral pristinamycin therapy at the Peter MacCallum Cancer Centre between January 2005 and December 2014 were identified using the hospital pharmacy dispensing system. Information on demographics, co-morbidities, cancer diagnosis, infection characteristics, pristinamycin regimen, pristinamycin tolerability and outcomes was collected. The median duration of follow-up was 398 days. In total, 26 patients received pristinamycin, with median age of 61 years and a male predominance (65%). Underlying diagnoses were haematological malignancies (50%) and solid tumours (50%). Pathogens included 13 meticillin-resistant Staphylococcus aureus, 6 vancomycin-resistant Enterococcus faecium, 4 meticillin-resistant Staphylococcus epidermidis, 2 meticillin-susceptible S. aureus and 1 vancomycin-susceptible E. faecium. Infection sites were osteomyelitis (6), skin and soft-tissue (4), intra-abdominal/pelvic abscess (4), bloodstream (3), empyema (3), endocarditis/endovascular (3), prosthesis-related infection (2) and epididymo-orchitis (1). One patient ceased pristinamycin due to nausea. Regarding outcome, 13 patients (50%) were cured of infection, 8 (31%) had suppression and 5 (19%) had relapse. Relapses included 1 endovascular infection, 2 episodes of osteomyelitis, 1 pelvic abscess and 1 skin and soft-tissue infection. Overall, 81% of patients achieved cure or suppression of antibiotic-resistant or complex Gram-positive infections, consistent with published experience in non-cancer populations. A favourable tolerability profile makes oral pristinamycin a viable treatment option, particularly in settings where outpatient management of cancer is the objective.

The basophil activation test: a sensitive test in the diagnosis of allergic immediate hypersensitivity to pristinamycin.

Immediate hypersensitivity (IHS) reactions to macrolides and to macrolide-derived antibiotics like pristinamycin are uncommon. In this context, there is little data available to appreciate the true value of biological tools regarding the diagnosis of immediate allergy to pristinamycin. Here we assess the clinical usefulness of the basophil activation test (BAT) to differentiate allergic from nonallergic IHS to pristinamycin. Thirty-six patients were tested with skin tests as the gold standard and BAT. The BAT achieved a sensitivity of 76% and a specificity of 100%, implying an absence of false positive results. Multicenter studies remain to be performed to better define the sensitivity, specificity and interlaboratory variation of BAT in the diagnosis of allergy to pristinamycin and macrolides.

[Pristinamycin/Vitamin k antagonists drug interaction: a French pharmacovigilance database study]. / Interaction pristinamycine/antivitamine K: analyse de la base française de pharmacovigilance.

OBJECTIVE: To analyse pristinamycin/vitamin K antagonists (VKA) drug interaction by using data recorded in the French pharmacovigilance database (FPVB). METHODS: All cases with an increase effect of a VKA and an association with pristinamycin recorded in the FPVB between 1985 and 2013 were included. Data concerning patients, VKA treatments and side effects were recorded for a descriptive analysis. RESULTS: During this period, 31 reports with a VKA overdose after an association with pristinamycin were included. Fluindione is the most often involved VKA (77% of cases). In 20 cases (65.4%), VKA overdose caused bleeding and 24 cases (77.4%) were serious. CONCLUSION: Although mechanism is unknown, pristinamycine/AVK drug interaction is a reality that needs to be reported in the summary of product characteristics of these drugs and better known by practitioners to act in patients' interest.

Pristinamycin for Rickettsia africae infection.

African tick bite fever is caused by Rickettsia africae. The number of reported cases in international travelers has significantly increased recently. The gold standard treatment is doxycycline. Here, we present a case of R africae infection associated with quick complete resolution following the initiation of pristinamycin therapy.

[Staphylococcic necrotizing pneumopathy due to Panton-Valentine leukocidin toxin with good outcome]. / Pneumopathie nécrosante staphylococcique productrice de leucocidine de Panton-Valentine d'évolution favorable.

Panton-Valentine leukocidin (PLV) is a toxin produced by Staphylococcus aureus. Previously described as responsible for furunculoses and cutaneous abscesses, it was recently found to cause necrotizing pneumonia, generally lethal. We describe a case of necrotizing pneumonia caused by S. aureus containing PLV with an atypical form (bubble form), which had a good outcome despite several risk factors for death: hemoptysis, leukopenia, erythrodermia.

[French nationwide survey about management of acute osteomyelitis in children]. / Enquête nationale sur la prise en charge des ostéomyélites aiguës de l'enfant.

PURPOSE: The outcome of acute osteomyelitis in children has been modified by the use of potent antibiotics. However, treatment management remains unclear. The aim of this study was to investigate the current management of acute osteomyelitis in children in France. PATIENTS AND METHODS: A questionnaire regarding the choice and the duration of antibiotics was sent to French pediatricians and pediatric orthopedists. RESULTS: Ninety-four centers answered the questionnaire: 72 pediatricians and 22 pediatric orthopedists. The response rate was 51% and the median number of children hospitalized per year for osteomyelitis was 4 in each center. The radiologic procedures most often used for diagnosis were X-rays (99%) and bone scintigraphy (82%). Two intravenous antibiotics schemes were used by 80% of centers: either an association of 3rd-generation cephalosporin plus fosfomycin or an association of penicillin M and aminoglycoside, followed by oral penicillin M or pristinamycin. Intravenous therapy lasted 7 to 14 days in 72% of the centers. The total duration of antibiotic therapy was 6 weeks for 55% of centers. In 83% of cases, immobilization was prescribed. The decision for treatment withdrawal was based on clinical, biological or empirical findings for 59, 75 and 60% of departments, respectively. CONCLUSION: In spite of controversies and lack of consensus, regarding both the diagnostic procedures and treatment management, 2 main antibiotic therapy schemes emerged from our survey. However, the treatment duration appeared more variable. Reaching a consensus for acute-osteomyelitis care in children remains a critical issue.

Extensive cutaneous larva migrans with folliculitis mimicking multimetameric herpes zoster presentation in an adult traveler returning from Thailand.

Hookworm-related cutaneous larva migrans (CLM) is a frequent cutaneous disease among travelers returning from the tropics. It can be misdiagnosed or treated incorrectly. We present a 42-year-old French patient who contracted the disease during a holiday in Thailand and who experienced an extensive CLM syndrome with a less frequent abdominal localization and a pseudo-multimetameric homolateral topography. The condition was late diagnosed and secondarily efficiently cured by a unique administration of ivermectin. Simple anamnestic information--often revealing beach activities--and clinical aspect of the creeping eruption allow to prevent diagnosis delay and to avoid aggressive or inadequate intervention.

Cloxacillin versus pristinamycin for superficial pyodermas: a randomized, open-label, non-inferiority study.

BACKGROUND: Superficial pyodermas may require systemic antibiotics. In a previous open-label trial, oxacillin and pristinamycin achieved similar cure rates, but its design was not truly that of a non-inferiority study. OBJECTIVES: To assess the efficacy and safety of oral cloxacillin versus pristinamycin (both 2 g/day) to treat superficial pyodermas. METHODS: Multicentre, parallel-group, open-label, randomized non-inferiority trial. RESULTS: French general practitioners in private practice included 334 out-patients (mean age: 42 years). At the follow-up (day 14), the cure rates (primary efficacy end point) for the intent-to-treat populations were 80.7% (138/171) for cloxacillin and 82.8% (135/163) for pristinamycin. The observed difference between cure rates was -2.1%, with the lower limit of the two-sided 95% confidence interval higher than the non-inferiority threshold of -15%. The per-protocol analysis yielded similar results. Therapy was discontinued for 10 patients (cloxacillin: 1, pristinamycin: 9; p = 0.01). CONCLUSION: Cloxacillin could be an alternative to pristinamycin in out-patients with superficial pyodermas.

Successful oral pristinamycin therapy for osteoarticular infections due to methicillin-resistant Staphylococcus aureus (MRSA) and other Staphylococcus spp.

OBJECTIVES: Oral treatment regimens for multiresistant methicillin-resistant Staphylococcus aureus (MRSA) infections are limited. In Australia, rifampicin plus fusidic acid is the usual treatment regimen following glycopeptide therapy but many patients are intolerant of this; some isolates are resistant; new oxazolidinones are expensive for routine use. Pristinamycin is a possible alternative and we report our experience with this agent. METHODS: The Department of Microbiology and Infectious Diseases, South Western Area Pathology Service treats patients drawn from the South Western Sydney Area Health Service that houses approximately 800,000 people and contains approximately 2000 acute care public hospital beds. Patients prescribed pristinamycin between 1 September 2000 and 31 January 2000 were identified from hospital pharmacy records. A retrospective chart review was performed. Accepted clinical definitions of osteomyelitis and septic arthritis were used. RESULTS: Twenty-seven patients were identified with osteoarticular infections. Twenty-four cases involved Staphylococcus aureus (multiresistant MRSA in 21 cases); three involved Staphylococcus epidermidis sensu stricto; four cases involved multiple organisms. Nineteen cases received pristinamycin monotherapy; the others received various combinations (fusidic acid with five; other antibiotics with three). Therapy was generally well tolerated; no haematological or biochemical toxicity was detected. Seven patients had minor gastrointestinal disturbance; and one developed rash. Four patients required dose reduction. Only four patients ceased pristinamycin due to intolerance. Treatment outcome was evaluated in 23 cases; cure was effected in 16 cases, five were successfully suppressed and two failed. There were no deaths. CONCLUSIONS: Oral pristinamycin is well tolerated and an important additional agent to treat osteoarticular infections with multiresistant MRSA and other staphylococci.

Sideroblastic anaemia during fusidic acid treatment.

OBJECTIVES AND METHODS: To describe cases of fusidic acid-associated sideroblastic anaemia from the French Pharmacovigilance database. RESULTS: Six cases of sideroblastic anaemia associated with oral fusidic acid treatment were retrieved. Four females and two males (mean age 65.3 yr) developed severe anaemia (mean haemoglobin level: 6.9 g/dL) within 32-190 d (mean: 81 d) of treatment. Bone marrow aspirates showed dyserythropoiesis and ringed sideroblasts in all patients. Four patients required repeated blood transfusions. After fusidic acid discontinuation in five patients, complete recovery was obtained. In one patient, rechallenge with fusidic acid resulted in recurrence of anaemia that resolved after definitive discontinuation of the drug. CONCLUSION: Our data indicate that fusidic acid should be added to the list of drugs that can cause sideroblastic anaemia.

[Efficiency of a four-day course of pristinamycin compared to a five-day course of cefuroxime axetil for acute bacterial maxillary sinusitis in adult outpatients]. / Efficacité comparée de la pristinamycine en quatre jours et du céfuroxime axétil en cinq jours dans le traitement des sinusites maxillaires aiguës bactériennes de l'adulte.

OBJECTIVE: The aim of this multicentric, randomized, double blind study was to demonstrate that a 4-day treatment with pristinamycin 1 g bid was as efficient as a 5-day treatment with cefuroxime axetil 250 mg bid in adults presenting with an acute maxillary sinusitis. DESIGN: The clinical diagnosis was based on the association of sub-orbital pain, purulent rhinorrhea and purulent discharge on the middle nasal meatus and was confirmed radiologically. A rhinoscopic bacteriologic sampling was made on the middle nasal meatus. RESULTS: Four hundred and eighty five patients were included in the study: in France (n = 301), Tunisia (n = 48), Poland (n = 69) and Argentina (n = 67) between January 2001 and February 2002. Cultures were positive in 199/434 patients (46%), mainly S. pneumoniae (34.2%), H. influenzae (21.5%), S. aureus (15.4%), and M. catharralis (7.9%). The clinical cure rate at day 12-19 in the per protocol population, the main study criterion, was equal to 91.4% (201/220) and 91.1% (195/214) respectively in the pristinamycin and cefuroxime axetil groups; delta = 0.14%; 95%CI: [-5.1%; 5.3%]. The non-inferiority of 4-day pristinamycin versus 5-day cefuroxime axetil was demonstrated. The efficacy at follow up after treatment (day 26-31) was 88.6% and 85.8% respectively, confirming the non-inferiority. The bacteriological cure rate at day 12-19 was 87% (87/100) and 87.9% (87/99) respectively. Both treatments were well tolerated. CONCLUSION: A 4-day course with pristinamycin 1 g bid is as effective as a 5-day course of cefuroxime axetil 250 mg bid in the treatment of acute maxillary sinusitis in adults.