A. Tarasi

Conservative Medical Therapy of Infections Following Osteosynthesis: a Retrospective Analysis of a Six-Year Experience

Abstract The conventional therapeutic approach to bone infection associated with osteosynthesis is based on the idea that microbial eradication is most readily achieved by removal of the foreign material together with adequate antimicrobial therapy. This strategy usually requires implantation of external fixation devices with additional discomfort to the patient. We report our experience with conservative medical and antimicrobial therapy without removal of the osteosynthesis until adequate bone callus deposition is documented by bone radiography scan. Twenty patients with infections associated with intramedullary nailing (9 patients), screws and plate (9 patients) or screws (2 patients) were treated between 1995 to 2000. Osteosynthesis implantation sites were tibia (7 patients), femur (6 patients), femur and tibia (1 patient), humerus (1 patient), others (5 patients). Diagnosis of infection was based on clinical-microbiological evidence and confirmed by 99Tc-labeled leukocyte scan studies. Offending pathogens were Staphylococcus aureus 17 cases, Staphylococcus aureus + Escherichia coli, Staphylococcus epidermidis, unknown, 1 case each. Most infections were initially treated with intravenous or intramuscular teicoplanin ± ciprofloxacin or rifampin followed by oral antimicrobial therapy usually with ciprofloxacin or minocycline plus rifampin. Mean duration of antimicrobial therapy was 27.7 weeks (range 12-64 weeks). All patients (100%) were cured, and none complained of side-effects requiring antibiotic therapy discontinuation. We conclude that conservative medical therapy is feasible for osteosynthesis-associated bone infection.

High rate of oxacillin-resistant Staphylococcus aureus isolates in an Italian University Hospital.

We reviewed our routine clinical laboratory records from January 1990 to March 1993 to evaluate the rate of oxacillin-resistance among nosocomial isolates of Staphylococcus aureus. Of 265 clinically significant isolates, 174 (65%) were oxacillin-resistant S. aureus (ORSA). Most of these strains were obtained from surgery patients and/or were isolated from surgical wounds. The isolations of S. aureus increased during the study period: 45 in 1990, 50 in 1991, 130 in 1992 and 40 in the first trimester of 1993. The annual rates of ORSA among S. aureus isolated varied from 62 to 68% through these years. Most ORSA isolates proved resistant to ciprofloxacin, gentamicin and rifampicin, and susceptible to vancomycin, netilmicin and cotrimoxazole. Based on these results, the need for a stringent application of infection control measures is outlined.

Activity of moxifloxacin in combination with vancomycin or teicoplanin against Staphylococcus aureus isolated from device-associated infections unresponsive to glycopeptide therapy

Abstract We tested the in vitro bactericidal activity of moxifloxacin, a new 8-methoxyquinolone, alone and in combination with vancomycin or teicoplanin at different multiples of minimum inhibitory concentration (MIC) against 8 methicillin-ciprofloxacin-resistant Staphylococcus aureus (M-C-RSA) and 1 methicillin-ciprofloxacin susceptible S. aureus (M-C-SSA) recently isolated from device-associated infections unresponsive to or relapsing after glycopeptide therapy, despite device removal. MICs of vancomycin ranged from 1 to 4 μg/ml, MICs of teicoplanin ranged from 2 to 8 μg/ml; MICs of moxifloxacin were always 2 μg/ml against M-CRSA isolates and 0.125 μg/ml against the M-C-SSA isolate. The 9 strains resulted tolerant when tested for vancomycin, teicoplanin, and moxifloxacin used alone at 2xMIC. In all cases the combination of moxifloxacin and teicoplanin or vancomycin appeared to be bactericidal already at MIC concentration for glycopeptides plus 0.5xMIC concentration for moxifloxacin. If these results are confirmed in vivo in animal experiments, the combination of moxifloxacin with glycopeptides might be useful for treating device-associated infections, and in preventing the frightening phenomenon of increasing MICs for glycopeptides.

Potential of clindamycin in addition to vancomycin for the treatment of oxacillin-resistant Staphylococcus aureus septicemia persisting under vancomycin therapy

We observed seven patients with persistent fever and staphylococcemia under vancomycin-containing antimicrobial regimens who promptly improved as clindamycin was added to the initial antibiotics. Moreover, in all these patients a striking increase in peak and trough serum inhibitory activity (SIR) and serum bactericidal activity (SBA) levels was observed after addition of clindamycin. SIA and SBA levels after administration of a single dose of vancomycin (500 mg), clindamycin (600 mg) or vancomycin + clindamycin were also measured in three healthy volunteers against six ORSA isolates. Unsatisfactory peak SBA levels (0% of cases 1:8) were obtained after vancomycin administration. Vice versa, peak SBA levels 1:8 were obtained in 94% of the cases after clindamycin and in 100% of cases after vancomycin + clindamycin. Time-kill studies showed a borderline or incomplete bactericidal activity of vancomycin against three ORSA isolates from infections that manifested poor or slow response to vancomycin therapy. The combination with clindamycin did not result in a synergistic interaction between the two drugs. It is concluded that addition of clindamycin may be useful in some cases of ORSA septicemia that show poor or slow response to vancomycin therapy. The recommendation for a wider use of this combination of antibiotics requires further documentation of efficacy.

Alterations of coagulase-negative staphylococcal flora in cardiac surgery patients: comparative study between cefamandole and pefloxacin perioperative prophylaxis.

The changes in coagulase-negative staphylococcal flora induced by cefamandole prophylaxis were compared with those induced by pefloxacin prophylaxis among patients undergoing heart valve surgery. Twenty-five patients (15 receiving cefamandole prophylaxis and 10 receiving pefloxacin prophylaxis) were included in the study. In the pefloxacin group, colonization rates in anterior nares and in chest skin or wound that were 60% and 50% respectively before surgery, became 50% and 20% respectively after surgery. In the cefamandole group, colonization rates in anterior nares and chest skin or wound were 53.3% and 60% respectively before surgery and became 53.3% and 40% respectively after surgery. Cefamandole did not appear to induce the emergence of oxacillin or pefloxacin resistant coagulase-negative staphylococcal colonization in any cultured site. On the other hand pefloxacin appeared somewhat more efficacious than cefamandole in eradicating staphylococcal flora of anterior nares and chest skin or wound. Pefloxacin and oxacillin resistant strains were found in the perianal area in 0% of patients before pefloxacin prophylaxis and in 70% of patients after pefloxacin prophylaxis. However, further studies are necessary to confirm the emergence of antibiotic resistant coagulase-negative staphylococci in the intestinal microflora after quinolone administration. The clinical implications of such apparently disturbing phenomenon remain to be evaluated.

The activity ‘in vitro’ of trospectomycin against high-level antibiotic-resistant enterococci

Trospectomycin, a new aminocyclitol antibiotic, was uniformly active against 69 isolates of enterococci with high-level resistance to steptomycin (54 isolates), gentamicin (27 isolates), ampicillin (19 isolates), ciprofloxacin (17 isolates), vancomycin (3 isolates), or teicoplanin (3 isolates). In time-killing studies, trospectomycin alone demonstrated no bactericidal activity. No synergistic interaction was demonstrated when trospectomycin was combined with ampicillin, vacomycin or ciprofloxacin.

Intravenous ciprofloxacin for the treatment of severe infections.

Intravenous ciprofloxacin at a daily dosage of 400 mg divided in two doses was administered to 19 patients with severe infections caused by ciprofloxacin-susceptible bacteria. These infections included: 11 surgical would infections, 5 soft tissue infections, 2 respiratory tract infections, 1 urinary tract infection. The offending pathogens were: 8 coagulase-negative staphylococci, 3 Staphylococcus aureus, 3 Pseudomonas aeruginosa, 2 Proteus spp., 1 Escherichia coli, 1 Branhamella catarrhalis, 1 Klebsiella ozenae and 1 Serratia liquefaciens. Overall, 17 of 19 infections (89%) showed a satisfactory clinical response to trial therapy (15 cures and 2 improvements). Microbiological eradication was observed in 17 out of 20 isolated pathogens. Emergence of resistance to ciprofloxacin occurred in 1 coagulase-negative Staphylococcus and was associated with clinical failure. No side effects were observed. We conclude that intravenous ciprofloxacin may represent efficacious and safe therapy of severe infections; however close microbiological monitoring seems to be necessary to evaluate the emergence of resistance during quinolone therapy.