J. Cabo

Group B streptococcus (Streptococcus agalactiae) pyogenic arthritis in nonpregnant adults.

We analyzed the cases of pyogenic arthritis from group B streptococcus (GBS), or Streptococcus agalactiae, in nonpregnant adults diagnosed in the Hospital Universitari de Bellvitge, a 1,000-bed tertiary care teaching hospital in Barcelona, Spain, during a 10-year period, and we reviewed the available literature to summarize the experience with this infectious entity. From the database of our institution, which does not attend pediatric, obstetric, or burn patients, we collected all microbiologically proven cases of infectious arthritis seen from January 1992 to December 2001. We excluded patients with infection limited to spine; patients with prosthetic joint infection; patients undergoing articular surgery during the year before diagnosis; and those with tuberculous, brucellar, or fungal arthritis. Of a total of 112 patients identified, GBS was the causative organism in 11 (10%) cases. We reviewed the literature using a MEDLINE search (1972–2001), and found 64 additional cases.Of the 75 patients, 34 (45%) were men and 41 (55%) women, with ages ranging from 20 to 87 years (mean age, 57.9 ± 14.9 yr); 37 patients (49%) were over 60 years. Sixty-eight percent (51/75) of the patients presented with monoarthritis, while in 32% (24/75) more than 1 joint was involved. The most common location was the knee (36%), followed by the shoulder (25%). In 66% (43/65) of cases, bacteremia was documented. In 64% (47/74) of patients, a systemic predisposing factor for infection was noted; the most common conditions were diabetes mellitus, malignancies, and chronic liver diseases. In 31% (23/75) of patients, a concomitant infectious process due to the same microorganism was found, mainly vertebral osteomyelitis and urinary tract infection. Penicillin was the main antibiotic used after bacterial identification; surgical drainage was performed in 36% (27/75) of cases. The overall mortality rate was 9% (7/75).GBS is now a significant causative agent of pyogenic arthritis in nonpregnant adults. In this population, joint infection by GBS is a disease that mainly affects aged patients with underlying medical illnesses; polyarticular involvement, bacteremia, and the presence of a concomitant infectious process are frequent conditions. The case-fatality rate is substantial.

Efficacy of Usual and High Doses of Daptomycin in Combination with Rifampin versus Alternative Therapies in Experimental Foreign-Body Infection by Methicillin-Resistant Staphylococcus aureus†

ABSTRACT The treatment of prosthetic joint infections caused by methicillin-resistant Staphylococcus aureus (MRSA) continues to be a challenge for the clinician. The aim of this study was to evaluate the efficacies of daptomycin at usual and high doses (equivalent to 6 and 10 mg/kg of body weight/day, respectively, in humans) and in combination with rifampin and to compare the activities to those of conventional anti-MRSA therapies. We used MRSA strain HUSA 304, with the following MICs and minimal bactericidal concentrations (MBCs), respectively: daptomycin, 1 μg/ml and 4 μg/ml; vancomycin, 2 μg/ml and 4 μg/ml; linezolid, 2 μg/ml and >32 μg/ml; and rifampin, 0.03 μg/ml and 0.5 μg/ml. In time-kill curves, only daptomycin and its combinations with rifampin achieved a bactericidal effect in log and stationary phases. For in vivo studies, we used a rat foreign-body infection model. Therapy was administered for 7 days with daptomycin at 100 mg/kg/day and 45/mg/kg/day, vancomycin at 50 mg/kg/12 h, rifampin at 25 mg/kg/12 h, and linezolid at 35 mg/kg/12 h, and each antibiotic was also combined with rifampin. Among monotherapies, daptomycin at 100 mg/kg/day and rifampin performed better than vancomycin and linezolid. In combination with rifampin, both dosages of daptomycin were significantly better than all other combinations, but daptomycin at 100 mg/kg/day plus rifampin achieved better cure rates at day 11 (P < 0.05) than daptomycin at 45 mg/kg/day plus rifampin. Resistant strains were found in monotherapies with rifampin and daptomycin at 45 mg/kg/day. In conclusion, daptomycin at high doses was the most effective monotherapy and also improved the efficacy of the combination with rifampin against foreign-body infections by MRSA. Clinical studies should confirm whether this combination may be considered the first-line treatment for foreign-body infections by MRSA in humans.

Efficacy of High Doses of Daptomycin versus Alternative Therapies against Experimental Foreign-Body Infection by Methicillin-Resistant Staphylococcus aureus

ABSTRACT Since the currently approved dose of daptomycin (6 mg/kg of body weight/day) has been associated with clinical failures and resistance development, higher doses for some difficult-to-treat infections are being proposed. We studied the efficacy of daptomycin at high doses (equivalent to 10 mg/kg/day in humans) and compared it to that of reference and alternative treatments in a model of foreign-body infection with methicillin (meticillin)-resistant Staphylococcus aureus. In vitro studies were conducted with bacteria in the log and stationary phases. For the in vivo model, therapy with daptomycin at 100 mg/kg/day, vancomycin at 50 mg/kg/12 h, rifampin (rifampicin) at 25 mg/kg/12 h, or linezolid at 35 mg/kg/12 h was administered for 7 days. Antibiotic efficacy was evaluated using either bacteria from tissue cage fluids or those attached to coverslips. We screened for the emergence of linezolid- and rifampin-resistant strains and analyzed the surviving population from the daptomycin-treated group. Only daptomycin was bactericidal in both the log- and stationary-phase studies. Daptomycin (decrease in the log number of CFU per milliliter of tissue cage fluid, 2.57) and rifampin (decrease, 2.6 log CFU/ml) were better (P < 0.05) than vancomycin (decrease, 1.1 log CFU/ml) and linezolid (decrease, 0.9 log CFU/ml) in the animal model. Rifampin-resistant strains appeared in 60% of cases, whereas no linezolid resistance emerged. No daptomycin-resistant subpopulations were detected at frequencies of 10−7 or higher. In conclusion, daptomycin at high doses proved to be as effective as rifampin, and the two were the most active therapies for this experimental foreign-body infection. These high doses ensured a profile of safety from the development of resistance.

Long-Term Follow-Up Trial of Oral Rifampin-Cotrimoxazole Combination versus Intravenous Cloxacillin in Treatment of Chronic Staphylococcal Osteomyelitis

ABSTRACT Oral therapies alternative to fluoroquinolones against staphylococcal chronic osteomyelitis have not been evaluated in comparative studies. Consecutive nonaxial Staphylococcus aureus chronic osteomyelitis cases were included in a comparative trial after debridement. Fifty patients were randomized: group A (n = 22) was treated with cloxacillin for 6 weeks intravenously plus 2 weeks orally (p.o.), and group B (n = 28) was treated with rifampin-cotrimoxazole for 8 weeks p.o. During follow-up (10 years), five relapses occurred: two (10%) in group A and three (11%) in group B. Foreign-body maintenance was associated with relapse (P = 0.016). Oral rifampin-cotrimoxazole treatment showed outcomes comparable to those for intravenous cloxacillin treatment.

Fosfomycin-Daptomycin and Other Fosfomycin Combinations as Alternative Therapies in Experimental Foreign-Body Infection by Methicillin-Resistant Staphylococcus aureus

ABSTRACT The efficacy of daptomycin, imipenem, or rifampin with fosfomycin was evaluated and compared with that of daptomycin-rifampin in a tissue cage model infection caused by methicillin-resistant Staphylococcus aureus (MRSA). Strain HUSA 304 was used. The study yielded the following results for MICs (in μg/ml): fosfomycin, 4; daptomycin, 1; imipenem, 0.25; and rifampin, 0.03. The study yielded the following results for minimum bactericidal concentration (MBC) (in μg/ml): fosfomycin, 8; daptomycin, 4; imipenem, 32; and rifampin, 0.5. Daptomycin-rifampin was confirmed as the most effective therapy against MRSA foreign-body infections. Fosfomycin combinations with high doses of daptomycin and rifampin were efficacious alternative therapies in this setting. Fosfomycin-imipenem was relatively ineffective and did not protect against resistance.

Antagonistic Effect of Rifampin on the Efficacy of High-Dose Levofloxacin in Staphylococcal Experimental Foreign-Body Infection

ABSTRACT Since levofloxacin at high doses was more active than levofloxacin at conventional doses and was the best therapy alone in a rat model of staphylococcal foreign-body infection, in this study we tested how these differences affect the activities of their respective combinations with rifampin in vitro and in vivo. In vitro studies were performed in the log and stationary phases. By using this model, rifampin at 25 mg/kg of body weight/12 h, levofloxacin at 100 mg/kg/day, levofloxacin at 100 mg/kg/day plus rifampin, levofloxacin at 50 mg/kg/day, levofloxacin at 50 mg/kg/day plus rifampin, or a control treatment was administered for 7 days; and therapy with for levofloxacin at 100 mg/kg/day alone and rifampin alone was prolonged to 14 days. We screened for the appearance of resistant strains. Killing curves in the log phase showed a clear antagonism with levofloxacin at concentrations ≥2× MIC and rifampin and tended to occur in the stationary phase. At the end of 7 days of therapy, levofloxacin at 100 mg/kg/day was the best treatment and decreased the bacterial counts from tissue cage fluid (P < 0.05 compared with the results for groups except those receiving rifampin alone). At the end of 14 days of therapy with levofloxacin at 100 mg/kg/day, levofloxacin at 100 mg/kg/day plus rifampin, and the control treatment, the bacterial counts on the coverslips were 2.24 (P < 0.05 compared with the results with the combined therapy), 3.36, and 5.4 log CFU/ml, respectively. No rifampin or levofloxacin resistance was detected in any group except that receiving rifampin alone. In conclusion, high-dose levofloxacin was the best treatment and no resistant strains appeared; the addition of rifampin showed an antagonistic effect. The efficacy of the rifampin-levofloxacin combination is not significantly improved by the dosage of levofloxacin.

Pilot Study of Ampicillin-Ceftriaxone Combination for Treatment of Orthopedic Infections Due to Enterococcus faecalis

ABSTRACT Serious Enterococcus faecalis infections usually require combination therapy to achieve a bactericidal effect. In orthopedic infections, the prognosis of enterococcal etiology is considered poor, and the use of aminoglycosides is questioned. The ampicillin-ceftriaxone combination has recently been accepted as alternative therapy for enterococcal endocarditis. After one of our patients with endocarditis and vertebral osteomyelitis was cured with ampicillin-ceftriaxone, we started a pilot study of orthopedic infections. Patients with infections due to E. faecalis (with two or more surgical samples or blood cultures) diagnosed during 2005 to 2008 were recruited. Polymicrobial infections with ampicillin- and ceftriaxone-resistant microorganisms were excluded. Patients received ampicillin (8 to 16 g/day)-ceftriaxone (2 to 4 g/day) and were followed up prospectively. Of 31 patients with E. faecalis infections, 10 received ampicillin-ceftriaxone. Including the first patient, 11 patients were treated with ampicillin-ceftriaxone: 3 with prosthetic joint infections, 3 with instrumented spine arthrodesis device infections, 2 with osteosynthesis device infections, 1 with foot osteomyelitis, and 2 with vertebral osteomyelitis and endocarditis. Six infections (55%) were polymicrobial. All cases except the vertebral osteomyelitis ones required surgery, with retention of foreign material in six cases. Ampicillin-ceftriaxone was given for 25 days (interquartile range, 15 to 34 days), followed by amoxicillin (amoxicilline) being given to seven patients (64%). One patient with endocarditis died within 2 weeks (hemorrhagic stroke) and was not evaluable. For one patient with prosthesis retention, the infection persisted; 9/10 patients (90%) were cured, but 1 patient was superinfected. Follow-up was for 21 months (interquartile range, 14 to 36 months). Ampicillin-ceftriaxone may be a reasonable synergistic combination to treat orthopedic infections due to E. faecalis. Our experience, though limited, shows good outcomes and tolerability and may provide a basis for further well-designed comparative studies.

Efficacy of Daptomycin-Cloxacillin Combination in Experimental Foreign-Body Infection Due to Methicillin-Resistant Staphylococcus aureus

ABSTRACT Despite the use of daptomycin alone at high doses (greater than 6 mg/kg of body weight/day) against difficult-to-treat infections, clinical failures and resistance appeared. Recently, the combination daptomycin-cloxacillin showed enhanced efficacy in clearing bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to evaluate the efficacy of daptomycin at usual and high doses (equivalent to 6 and 10 mg/kg/day in humans, respectively) in combination with cloxacillin in a rat tissue cage infection model by MRSA and to compare its efficacy to that of daptomycin-rifampin. We used MRSA strain ATCC BAA-39. In the log- and stationary-phase kill curves, daptomycin-cloxacillin improved the bactericidal activity of daptomycin, especially in log phase. For in vivo studies, therapy was administered intraperitoneally for 7 days with daptomycin at 100 mg/kg/day and 45/mg/kg/day (daptomycin 100 and daptomycin 45), daptomycin 100-cloxacillin at 200 mg/kg/12 h, daptomycin 45-cloxacillin, and daptomycin 100-rifampin at 25 mg/kg/12 h. Daptomycin-rifampin was the best therapy (P < 0.05). Daptomycin 45 was the least effective treatment and did not protect against the emergence of resistant strains. There were no differences between the two dosages of daptomycin plus cloxacillin in any situation, and both protected against resistance. The overall effect of the addition of cloxacillin to daptomycin was a significantly greater cure rate (against adhered bacteria) than that for daptomycin alone. In conclusion, daptomycin-cloxacillin enhanced modestly the in vivo efficacy of daptomycin alone against foreign-body infection by MRSA and was less effective than daptomycin plus rifampin. The benefits of adding cloxacillin to daptomycin should be especially evaluated against infections by rifampin-resistant MRSA and for protection against the emergence of daptomycin nonsusceptibility.

Efficacy of linezolid alone and in combination with rifampin in staphylococcal experimental foreign-body infection

OBJECTIVES The knowledge about efficacy of linezolid alone or in combination with rifampin in device infections is limited. We test their in vitro and in vivo efficacy in a rat model of foreign-body infection by methicillin-susceptible S. aureus. METHODS In vitro studies for logarithmic and stationary bacteria were performed. In vivo efficacy (decrease in bacterial counts in tissue cage fluid) was evaluated at: (i) after 7-day therapy (groups: linezolid, cloxacillin, rifampin, linezolid-rifampin and cloxacillin-rifampin); and (ii) after 10-day therapy (groups: rifampin and linezolid-rifampin). RESULTS After 7-day therapy all groups were significantly better than controls; linezolid (Delta log cfu/ml: -0.59, no resistant strains) and cloxacillin (-0.85) were the least effective therapy; linezolid was significantly less active (P<0.05) than rifampin (-1.22, resistance 90%), cloxacillin-rifampin (-1.3) and linezolid-rifampin (-1.14). After 10-day therapy linezolid-rifampin was the most effective treatment (Delta log -1.44, no resistance, P<0.05); in contrast, rifampin resulted ineffective (Delta log 0.1) due to the growth of resistant strains (100%). CONCLUSIONS Linezolid alone showed moderate efficacy, whereas its combination with rifampin prevented the emergence of rifampin resistance. The efficacy of linezolid-rifampin combination was initially similar to that of rifampin alone, but in contrast to rifampin, it increased over time revealing the impact of protection against rifampin resistance and the benefits of rifampin activity.

Pyogenic arthritis of native joints in non-intravenous drug users: A detailed analysis of 268 cases attended in a tertiary hospital over a 22-year period

OBJECTIVE To analyze the clinical features, microbiological spectrum, diagnostic procedures and outcomes in native joint pyogenic arthritis among non-intravenous drug users. METHODS We collected all microbiologically proved cases of infectious arthritis at our hospital between 1992 and 2013. Patients with prosthetic joint infection were excluded, as were patients with non-pyogenic arthritis and intravenous drug users. RESULTS We identified 268 patients; the mean age was 61 ± 14.7 years and 62% were men. The incidence increased over the period of study. In 188 patients (70%), one or more underlying medical illnesses were found. The mean symptom duration was 8.9 ± 9.5 days. Globally, 311 affected joints were found, 232 (75%) involving peripheral joints and 79 (25%) axial joints. Staphylococci (55%) and Streptococci (29%) were the predominant microorganisms. Blood cultures were positive in 78% (173/223) of the cases. In 81 patients (30%), one or more concomitant infectious processes were found. Antimicrobial therapy was prescribed 4-8 weeks in most cases, and surgical drainage was performed in 65% of patients. Four patients relapsed and 23 (8%) died. CONCLUSIONS The prevalence of pyogenic native joint arthritis in non-intravenous drug users is increasing, frequently affecting old patients with underlying medical conditions. Although large joints are the most frequently compromised, the involvement of axial joints is a relevant feature that has not been recognized in other series. Staphylococci and Streptococci are the main causative agents. Bacteremia and concomitant infectious processes are frequent complications. Diagnostic delay and mortality continue to be important concerns.