Management of prosthetic joint infection (PJI) remains a therapeutic challenge. We retrospectively studied 69 infected total hip or knee arthroplasties managed between 1980 and 1996 in our institution. Treatment failure, defined as relapse of PJI in the first year following the last antimicrobial treatment, occurred for 14 patients (20.3%). None of the potentially contributive parameters analyzed was significantly predictive of treatment failure. Of the subgroup of 34 patients with PJI who initially underwent debridement with retention of the prosthesis, the 13 (38.2%) who did not require further surgical treatment had symptoms for a significantly shorter duration before debridement (4.85 vs. 54.24 days; P < .0001). Because debridement with retention of the prosthesis rarely enables control of PJI, this therapeutic approach should be considered only when the duration of symptoms is very short.

BackgroundExtensive spread of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in the United States, and the concomitant increase in severe invasive staphylococcal infections, including osteomyelitis, in healthy children, has led to renewed interest in Panton-Valentine leukocidin (PVL). However, the pathogenetic role of PVL in staphylococcal infections remains controversial, possibly because it depends on the site of infection.Methodology/Principal FindingsWe compared the course of experimental rabbit osteomyelitis due to the PVL-positive CA-MRSA strain USA 300 (LAC) and its PVL-negative isogenic derivative (LACΔpvl), using a low and a high inoculum (8×105 and 4×108 CFU). With the low inoculum, bone infection was less frequent on day 7 (D7) and day 28 (D28) with LACΔpvl than with LAC (respectively 12/19 and 18/19 animals, p = 0.042). With the high inoculum of both strains, all the animals were infected on D7 and the infection persisted on D28 in almost every case. However, tibial bacterial counts and the serum CRP concentration fell significantly between D7 and D28 with LACΔpvl but not with LAC. Respectively 67% and 60% of LAC-infected rabbits had bone deformation and muscle/joint involvement on D7, compared to 0% and 7% of LACΔpvl-infected rabbits (p = 0.001 and p = 0.005 respectively). Between D0 and D28, the anti-PVL antibody titer increased significantly only with the high inoculum of LAC.Conclusions/SignificancePVL appears to play a role in the persistence and rapid local extension of rabbit osteomyelitis, in keeping with the greater severity of human bone infections due to PVL-positive S. aureus. The possible therapeutic implications of these findings are discussed.

Nontargeted HIV testing in EDs was feasible but identified only a few new HIV diagnoses, often at late stages, and, unexpectedly, most patients belonged to a high-risk group. Our findings do not support the implementation of nontargeted screening of the general population in EDs.

Daptomycin is an attractive option for treating prosthetic joint infection, but the 6-mg/kg of body weight/day dose was linked to clinical failure and emergence of resistance. Using a methicillin-resistant Staphylococcus aureus (MRSA) knee prosthesis infection in rabbits, we studied the efficacies of high-dose daptomycin ( d.). After partial knee replacement with a silicone implant, 107 MRSA CFU was injected into the knees. Treatment started 7 days postinoculation and lasted 7 days. Positive cultures were screened for the emergence of mutant strains, defined as having 3-fold-increased MICs. Although in vivo mean log 10 CFU/g of daptomycintreated (4.23 ؎ 1.44; n ‫؍‬ 12) or vancomycin-treated (4.63 ؎ 1.08; n ‫؍‬ 12) crushed bone was significantly lower than that of controls (5.93 ؎ 1.15; n ‫؍‬ 9) (P < 0.01), neither treatment sterilized bone (2/12 and 0/12 rabbits with sterile bone, respectively). Daptomycin mutant strains were found in 6/12, 3/12, and 2/9 daptomycintreated, vancomycin-treated, and control rabbits, respectively; no resistant strains emerged (MIC was always <1 mg/liter). Adjunctive rifampin with daptomycin (1.47 ؎ 0.04 CFU/g of bone [detection threshold]; 11/11 sterile bones) or vancomycin (1.5 ؎ 0.12 CFU/g of bone; 6/8 sterile bones) was significantly more effective than monotherapy (P < 0.01) and prevented the emergence of daptomycin mutant strains. In this MRSA joint prosthesis infection model, combining rifampin with daptomycin was highly effective. Daptomycin mutant strains were isolated in vivo even without treatment, but adjunctive rifampin prevented this phenomenon, previously found after monotherapy in humans.

The reason bacterial endocarditis is difficult to cure has been controversial for many years. One explanation could be that antibiotic diffusion inside the vegetations is heterogeneous. This hypothesis was investigated by means of an autoradiographic study of diffusion of labeled antibiotics into large infected cardiac vegetations of nutritionally variant Streptococcus endocarditis in rabbits. Ten days after infection, 653 microCi of [3H]penicillin, 410 microCi of [3H]tobramycin, or 174 microCi of [14C]teicoplanin were injected iv over 30 min. Thirty minutes after the end of infusion (T30), vegetation/blood radioactivity ratios were 2.48 +/- 1.27, 2.49 +/- 0.67, and 3.94 +/- 1.19 for penicillin, tobramycin, and teicoplanin, respectively. Autoradiography clearly showed that distribution of the three drugs was different: Tobramycin was homogeneously distributed; penicillin was more concentrated at the periphery but still reached the center of vegetations; teicoplanin was concentrated only at the periphery. The same distribution pattern was observed with teicoplanin at T120 (i.e., one t1/2 beta later) and also after simultaneous infusion of a therapeutic dose (15 mg/kg) of cold teicoplanin. The diffusion gradient exhibited by some antibiotics could explain the difficulty in sterilizing vegetations despite high local concentrations, and the deleterious effect of the size of the vegetations on the therapeutic response.

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Partial knee arthroplasty was done in rabbits with a silicone-elastomer implant. Immediately after closing the surgical wound, 5 x 10(6) cfu of methicillin-resistant Staphylococcus aureus was injected into the joint. Disease evolution was studied at different stages of infection up to 8 weeks. Prosthetic infection developed in all animals. Gross pathology and histopathologic changes were characteristic of joint and bone infection. Quantitative bacterial counts from infected bone confirmed disease chronicity. The mean number of colony-forming units per gram of bone +/- SD 1 week after infection was 4.84 +/- 0.24 log10 cfu/g and remained stable from week 1 to week 8. Magnetic resonance imaging showed evidence of prosthetic infection as of week 1, while only mild radiologic changes of bone were seen 2 weeks after infection. This model produces a prosthetic infection that is reproducible and close to that of human prosthetic infection.

Six different antibiotic treatment regimens were compared for efficacy in rabbits with endocarditis induced by inoculation with a nutritionally variant strain of streptococcus. Seven untreated animals, sacrificed at day 11, had vegetations containing 8.89 ± 1.35 logl0 CFU/g, none of which was sterile. The vegetations from the rabbits in all treated groups had bacterial titers significantly lower than those of the controls (P < 0.001).Vegetations from penicillin-treated animals averaged 5.14 ± 1.00 log CFU/g, and no vegetations were sterile. Treatment with penicillin plus gentamicin or amikacin was more effective than treatment with penicillin alone, resulting in 3.99 ± 0.94 log CFU/g of vegetation and sterile lesions in 5 of 12 animals. Treatment with vancomycin alone was as least as efficient as that with penicillin plus an aminoglycoside, resulting in an average of 3.33 ± 0.96 log CFU/g of vegetation and sterile lesions in five of eight animals. Treatment with vancomycin plus an aminoglycoside was not superior to treatment with vancomycin alone, resulting in an average of 3.68 ± 1.37 log CFU/g of vegetation and sterile lesions in 8 of 13 animals. These in vivo results correlated poorly with the in vitro susceptibility of the strain to the various antibiotics, as measured by the time-kill method. These results support the current practice of using vancomycin as alternative therapy when a penicillinaminoglycoside combination is ineffective or contraindicated in patients with endocarditis caused by nutritionally variant streptococci.