Clindamycin treatment of experimental chronic osteomyelitis due to Staphylococcus aureus

Clindamycin was used alone for treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Treatment with 30 mg/kg of body weight three times a day for 14 days was ineffective in sterilizing infected rabbit bones. In contrast, when given for 28 days, clindamycin sterilized the infected bones of 16 (84%) of 19 rabbits treated. Only one of 14 isolates of S. aureus from rabbits treated for two weeks developed resistance to clindamycin (minimal inhibitory concentration, greater than 100 micrograms/ml); none of three isolates from rabbits in which treatment failed in the four-week treatment group showed resistance to clindamycin. The results of four weeks of treatment with clindamycin for chronic experimental staphylococcal osteomyelitis were significantly better than those obtained with any other single agent used in prior studies and were generally as good as those with combination therapy that included rifampin.     

Experimental osteomyelitis. V. Therapeutic trials with oxacillin and sisomicin alone and in combination

Oxacillin was used alone and in combination with sisomicin in the treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Within diseased bone, levels of oxacillin and sisomicin remained higher than the minimal inhibitory concentration for 2 and 6 hr, respectively, after injection of 50 mg of oxacillin/kg and 10 mg of sisomicin/kg. Treatment with 50 mg of oxacillin/kg four times daily or 50 mg/kg every 4 hr around the clock for 28 days sterilized 30% of the rabbit bones. Sisomicin (10 mg/kg) injected twice daily for 28 days sterilized only 5% of the rabbit bones. In contrast, treatment with the combination of oxacillin and sisomicin for either 14 or 28 days was significantly more effective, sterilizing 78% and 85%, respectively, of the bones of treated animals. S. Aureus isolated from bones of animals treated with sisomicin alone contained aminoglycoside-resistant microcolonies. Resistant microcolonies were not recovered from animals treated with oxacillin or with the combination of oxacillin plus sisomicin. In vitro studies of bacterial killing by each antibiotic alone and in combination showed more bacterial killing with the combination than with either agent alone; in vitro the combination prevented emergence of resistant microcolonies. Combination antibiotic therapy appears to be more effective in treatment of experimental osteomyelitis due to S. aureus than therapy with a single agent.     

Treatment of experimental chronic osteomyelitis due to Staphylococcus aureus with ampicillin/sulbactam

Ampicillin/sulbactam was used for the treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Treatment with 200 mg/kg (ampicillin) three times a day sterilized 40% of infected rabbit bones. The results of 4 weeks of treatment with ampicillin/sulbactam for chronic experimental staphylococcal osteomyelitis were comparable to those obtained previously with cephalothin and with oxacillin in previous studies and were not as good as those with clindamycin alone or combination therapy that included rifampin.     

Experimental osteomyelitis. IV. Therapeutic trials with rifampin alone and in combination with gentamicin, sisomicin, and cephalothin.

Levels of rifampin, gentamicin, sisomicin, and cephalothin in normal and osteomyelitic rabbit bones were measured, and the efficacy of these drugs in the treatment of osteomyelitis was evaluated. Single drug regimens, including rifampin for 14 days and gentamicin, sisomicin, and cephalothin each for 28 days, were relatively ineffective (5%-33% sterile bone cultures). Rifampin, administered for 28 days, sterilized the bones of 55% of treated animals. The combination of gentamicin and rifampin, given for either 14 or 28 days, sterilized the bones of 67% of treated animals. The combinations of rifampin plus sisomicin and of rifampin plus cephalothin, given for 28 days, were significantly more effective than these agents alone, sterilizing 90%-95% of bones. The combination of rifampin, sisomicin, and cephalothin, given for only 14 days, sterilized the bones of all treated rabbits. Staphylococci isolated from the bones of therapeutic failures that had received rifampin alone or in combination with other antibiotics were highly resistant to rifampin (minimal inhibitory concentration, greater than 250 mug/ml), whereas the organisms recovered from animals not receiving rifampin remained sensitive. Results of in vitro studies of synergy and/or bactericidal activity of antibiotic combinations correlated with in vivo results in some, but not all, instances.     

Efficacy of vancomycin plus rifampin in experimental aortic-valve endocarditis due to methicillin-resistant Staphylococcus aureus: in vitro-in vivo correlations

Studies of in vitro and in vivo bactericidal interactions of vancomycin plus rifampin against Staphylococcus aureus have yielded conflicting results. In this study the efficacy of this drug combination in experimental endocarditis due to a methicillin-resistant strain of S. aureus was investigated. Left-sided endocarditis was induced in 84 rabbits by an infecting strain that had been found to be synergistically killed by vancomycin plus rifampin in vitro when tested by the timed-kill curve technique; in contrast, the checkerboard technique had indicated that the two drugs were antagonistic against this strain. Infected animals received no therapy, vancomycin alone (30 mg/kg per day), rifampin alone (20 mg/kg per day), or both drugs (in the same doses). The combination was significantly more effective than the single-drug regimens in terms of (1) reduction of mean methicillin-resistant S. aureus vegetation titers (P less than .05-.0005), (2) rate and incidence of sterilization of vegetations (P less than .0005), and (3) rate of "radical" cure of endocarditis (P less than .005). Vancomycin alone and vancomycin plus rifampin were equally effective in reducing mortality and sterilizing renal abscesses. The use of vancomycin prevented the in vivo development of resistance to rifampin. No evidence that rifampin exerted an antagonistic effect on the in vivo bactericidal activity of vancomycin was found.     

Efficacy of linezolid in the treatment of mediastinitis due to methicillin-resistant Staphylococcus aureus: an experimental study.

INTRODUCTION: The treatment of postoperative mediastinitis is very important because of its high morbidity, mortality, and increased hospital stay and hospital costs. The aims of our research were to investigate whether linezolid alone can be an effective treatment agent for methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis, and to determine whether linezolid can provide synergistic activity when given in combination with rifampin. METHODS: A partial upper median sternotomy was performed on 70 rats. The animals were divided into seven groups: an uncontaminated control group; an untreated contaminated group; three contaminated groups that received antibiotic therapy with either 25 or 50 mg/kg linezolid twice a day, or rifampin 5 mg/kg twice a day; and two contaminated groups that received a combination therapy consisting of 25 or 50 mg/kg linezolid and rifampin 5 mg/kg twice a day. The antibiotic treatment lasted 7 days. Tissue samples from the upper ends of the sternum and swab specimens of the upper mediastinum were obtained and evaluated microbiologically. RESULTS: The 25-mg/kg dose of linezolid, either alone or combined with rifampin, was not effective in reducing the bacterial counts in mediastinum and sternum. Quantitative bacterial cultures of mediastinum and sternum were significantly lower in the groups receiving 50 mg/kg linezolid alone or in combination with rifampin compared with the control. Adding of rifampin to linezolid therapy did not result in a significant change in bacterial counts versus linezolid alone. CONCLUSION: A high dose of linezolid should be considered as a possible therapeutic agent for the treatment of post-sternotomy infection caused by MRSA.     

Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis

OBJECTIVE: To determine the median response time to therapy with vancomycin alone or with vancomycin plus rifampin in patients with methicillin-resistant Staphylococcus aureus (MRSA) endocarditis. DESIGN: Cohort analysis of a randomized study. SETTING: University medical center. PATIENTS: Forty-two consecutive patients with MRSA endocarditis were randomly assigned to receive either vancomycin (group I) or vancomycin plus rifampin (group II) for 28 days. MEASUREMENTS: Clinical signs and symptoms were recorded, and blood cultures were obtained daily to determine the duration of bacteremia. MAIN RESULTS: The median duration of bacteremia was 9 days (7 days for group I and 9 days for group II). The median duration of fever for all patients and for each treatment group was 7 days. Six patients failed therapy, including three patients who died 5, 6, and 9 days after therapy was started, respectively. The other three patients who failed therapy required valve surgery on days 2, 22, and 27, respectively. Although patients had sustained bacteremia, no unusual complications were seen in either treatment group, and most patients responded to continued antibiotic therapy. CONCLUSIONS: Slow clinical response is common among patients with MRSA endocarditis who are treated with vancomycin or vancomycin plus rifampin. Nevertheless, few complications appear to be related solely to this sustained bacteremia.     

Treatment of experimental chronic osteomyelitis due to staphylococcus aureus with teicoplanin

Summary Teicoplanin was used alone in the treatment of experimental osteomyelitis due toStaphylococcus aureus in rabbits. Treatment with 60 mg of teicoplanin/kg of body weight twice a day for 28 days failed to sterilize any infected rabbit bones. A possible explanation for the failure of teicoplanin may be that itsin vitro activity against the infecting strain ofS. aureus was substantially less under anaerobic conditions (at partial pressures of oxygen analogous to those in osteomyelitic rabbit bones) than under aerobic conditions.

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Behandlung der experimentellen chronischen Staphylococcus aureus-Osteomyelitis mit Teicoplanin

Zusammenfassung Teicoplanin wurde als Einzelsubstanz zur Behandlung der experimentellenStaphylococcus aureus-Osteomyelitis bei Kaninchen verwendet. Keiner der infizierten Knochen konnte beim Kaninchen mit einer Behandlung mit 60 mg Teicoplanin/kg Körpergewicht zweimal täglich über 28 Tage keimfrei gemacht werden. Eine mögliche Erklärung für die ungenügende therapeutische Wirksamkeit von Teicoplanin bietet die Beobachtung, daß seine In vitro-Aktivität gegen den für die Infektion verwendeten Stamm vonS. aureus unter anaeroben Bedingungen (bei einem Sauerstoffpartialdruck, wie er im osteomyelitischen Kaninchenknochen chenknochen gefunden wird) erheblich geringer war als unter aeroben Bedingungen.

     

Rifampin resistance. Development during the therapy of methicillin-resistant Staphylococcus aureus infection

The incidence of methicillin-resistant staphylococcal infections, for which vancomycin hydrochloride remains the only active cell-wall antibiotic therapy, is rising. Some physicians have been combining other antibiotics with vancomycin in hopes of obtaining a more effective regimen for the therapy of these infections. Rifampin has been advocated as a concurrent second antibiotic because of its extraordinary potent bactericidal activity for Staphylococcus aureus. When rifampin is used in combination with a cell-wall antibiotic, suppression of the development of rifampin resistance has been thought possible. We report a case of infection caused by a methicillin-resistant S aureus in which the rifampin resistance occurred during therapy with vancomycin and rifampin. The rifampin resistance was stable and was present after ten serial broth and agar passages. Physicians are cautioned against the indiscriminant or routine use of rifampin as a second antibiotic in combination with vancomycin for the therapy of infections caused by S aureus.     

The effect of trimethoprim and sulfamethoxazole on Toxoplasma gondii in vitro and in vivo.

Trimethoprim (TMP) and sulfamethoxazole (SMZ) were studied alone and in combination to determine their effect in vitro on intracellular Toxoplasma gondii and in vivo against murine toxoplasmosis. In the in vitro experiments, whereas 1 and 2 microgram/ml TMP had no demonstrable effect on intracellular T. gondii, 10-20 microgram/ml TMP resulted in death of the intracellular organisms; concentrations as high as 100 microgram/ml SMZ had no demonstrable effect against the intracellular organisms. When used in combination, a significant synergistic effect was noted with 2 microgram/ml TMP-50 microgram/ml SMZ. Studies on the kinetics of inhibition and/or killing of Toxoplasma revealed that 18 hours of treatment with 2 microgram/ml TMP-50 microgram/ml SMZ resulted in irreversible inhibition of the intracellular organisms. When used in vivo against a 50,000 LD100 dose of Toxoplasma, TMP fed by gavage or mixed in the diet had no effect in murine toxoplasmosis at doses as high as 200 mg/kg a day. SMZ administered by gavage had no effect at doses up to 200 mg/kg a day; but at 300 and 400 mg/kg SMZ, protection was 47% and 83%, respectively. Treatment of infected mice was continued for 14 consecutive days, whether the drugs were administered alone or in combination. The combination 200 mg/kg TMP-200 mg/kg SMZ, when administered by gavage, protected 87% of mice. Survival after 14 days of SMZ mixed in the diet was 0% at 100 mg/kg, 47% at 200 mg/kg, and 100% at 300 mg/kg. Survival with the combination was 40% for 200 mg/kg TMP-100 mg/kg SMZ and 100% for 100 mg/kg TMP-200 mg/kg SMZ. The half-life of TMP in serum of Swiss Webster mice was calculated to be 24 min. The results obtained in vivo were inferior to those obtainable with the combination of pyrimethamine plus sulfadiazine. The problems of interpretation of results obtained in the murine model using TMP-SMZ and in their extrapolation to the treatment of the infection in man are discussed.     

Oral rifampin for eradication of Staphylococcus aureus carriage from healthy and sick populations: a systematic review of the evidence from comparative trials

BACKGROUND: Rifampin has been used for the eradication of Staphylococcus aureus (S. aureus) colonization in various populations of healthy and sick people. METHODS: We performed a systematic review of the evidence from randomized and nonrandomized controlled trials that compared the effectiveness and safety of a rifampin-based regimen with another regimen in eradicating S. aureus colonization from healthy and sick people. RESULTS: Nine comparative trials (6 of which were randomized controlled trials) were included in our analysis. S. aureus was eradicated more commonly in patients receiving rifampin-containing regimens compared to monotherapy with other systemic agents (ciprofloxacin, cloxacillin, minocycline, or vancomycin), both during early and late (>1 month after therapy) post treatment evaluations (odds ratio [OR] 46.2, 95% confidence interval [CI] 14.4-148, and OR 8.8, 95% CI 3.4-22.5 respectively, 4 studies included). There was no statistically significant difference between rifampin monotherapy and combinations of rifampin with other topical (bacitracin) or systemic (cloxacillin and minocycline) antibiotics in eradicating S. aureus both in early and late evaluations (OR 1.5, 95% CI 0.5-4.4, and OR 1.6, 95% CI 0.7-3.7, respectively, 3 studies included). Eradication of methicillin-resistant S. aureus (MRSA) varied according to the type and duration of the rifampin-containing regimen. It ranged from 25% for the combination of rifampin with trimethoprim/sulfamethoxazole for 5 days to 100% for the combination of oral rifampin and minocycline for 14 days. Discontinuation of rifampin due to drug-related toxicity was necessary in 2% of 282 studied patients. Development of resistance of S. aureus to rifampin during and after treatment with a regimen containing rifampin ranged from 0% to 40% (7 studies) and overall 17% of the 236 patients for whom relevant data was reported. CONCLUSION: The available evidence suggests that oral rifampin is an effective agent for the eradication of S. aureus carriage. However, development of antimicrobial resistance during and after treatment with rifampin occurs in a considerable proportion of patients; using rifampin in combination with another antimicrobial agent may decrease this resistance.     

Effects of PEGylated soluble tumor necrosis factor receptor type I (PEG sTNF-RI) alone and in combination with methotrexate in adjuvant arthritic rats.

OBJECTIVE: To determine the potential combination benefit of treatment with PEG sTNF-RI and methotrexate in adjuvant arthritic rats. METHODS: Lewis rats with adjuvant arthritis were treated by sc injections of either 3.0 or 0.3 mg/kg PEG sTNF-RI on days 9, 11, and 13 of adjuvant arthritis. The effects of PEG sTNF-RI treatment alone were compared to treatment with daily oral methotrexate (0.075, 0.06 or 0.045 mg/kg) or methotrexate in combination with PEG sTNF-RI. Efficacy was monitored by volume measurement of ankle joints, final paw weights and histologic evaluation with particular emphasis on bone lesions. RESULTS: Treatment with 3.0 or 0.3 mg/kg PEG sTNF-RI alone resulted in 52% or 28% inhibition, respectively, of paw swelling as assessed by final paw weight. Treatment with methotrexate at either 0.075, 0.06, or 0.045 mg/kg gave 84%, 51% or 18% inhibition and combination treatment resulted in additive inhibitory effects. Histologic evaluation of ankle joints demonstrated 68% or 25% inhibition of bone resorption with PEG sTNF-RI alone at 3.0 or 0.3 mg/kg. Treatment with 0.075, 0.06 or 0.045 mg/kg methotrexate resulted in 98%, 76% or 40% inhibition of bone resorption. Additive benefit was best seen with the lower doses of methotrexate. CONCLUSION: Combination therapy with PEG sTNF-RI and methotrexate results in additive benefit, with the final result being excellent inhibition of all arthritis parameters. Data from these studies supports the clinical investigation of the use of combination therapy of PEG sTNF-RI and methotrexate in rheumatoid arthritis patients.     

Anti-septicaemic effect of polysaccharide from Panax ginseng by macrophage activation

The aim of the present research was conducted to elucidate anti-septicaemic effect of a polysaccharide (PS) isolated from Panax ginseng C.A. Meyer (Araliaceae) by nitric oxide production from stimulated macrophage. In vitro assays for the activity measurement of PS, NO production test with Greiss reagent, phagocytic activity test using zymosan and cytokines production test using ELISA kit were also conducted. In vivo anti-septicaemic activity was assessed by using C57BL/6J mice. This was done with Staphylococcus aureus infection test. PS used at 0.025 mg/kg concentration showed a potent anti-septicaemic activity (80%, survival). However, it did not directly inhibit S. aureus in a minimum inhibitory concentration (MIC) test, conducted in vitro (data not shown). Nitric oxide production via macrophage activation showed the highest value of 5.5 nmol/ml at 1 microg/ml PS. In in vitro phagocytic activity test, PS at 10 microg/ml concentration showed a potent phagocytic activity for zymosan with 167% of the control. Production of TNF-alpha by macrophage activation at 10 microg/ml of PS was 96% lysis of L929. Also production of IL-1 and IL-6 by stimulation of macrophage with 100 microg/ml PS dose increased to 235 pg/ml and 0.47 ng/ml, respectively. The low mortality of PS treated (0.025 mg/kg) infected mice was concurrent with decreased bacterial content in the blood. Nitric oxide production in S. aureus infected mice whose macrophage was stimulated by PS (0.025 mg/kg) increased approximately 4 times than the untreated S. aureus infected group at 24 and 48 h incubation. In the PS treated (0.025 mg/kg) group, the intracellular concentration of S. aureus in macrophages decreased approximately by 50%, compared with the untreated group. Combine treatment with PS (0.025 mg/kg body weight) and vancomycin (10 mg/kg B.W.) resulted in 100% survival of the animals, whereas only 67% or 50% of the animals survived, respectively, when treated with PS or vancomycin alone. These results suggest that PS from Panax ginseng possess a potent anti-septicaemic activity by stimulating macrophage and a potentiality as an immunomodulator against sepsis occurred by Staphylococcus aureus.     

Further studies of the killing of M. leprae by aminoglycosides: reduced dosage and frequency of administration

The bactericidal activity of the aminoglycoside antibiotics streptomycin and kanamycin for Mycobacterium leprae in mice was assessed, both alone and in combination with rifampin, utilizing various dosage schedules. As in previous studies, 100 mg/kg five times weekly of streptomycin and kanamycin resulted, respectively, in 96% +/- 2% and 89% +/- 6% bactericide. Reducing the dosage of streptomycin to 50 mg/kg, 25 mg/kg, and even 12.5 mg/kg resulted in less but significant bactericidal activity. Such a reduction of kanamycin dosage resulted in no significant bactericidal activity. Reducing the frequency of administration of streptomycin (100 mg/kg) to twice weekly and once weekly resulted in a decreased but still significant killing of M. leprae; for kanamycin such a reduction in frequency of administration resulted in loss of bactericidal activity. Streptomycin when combined with rifampin was found more bactericidal than either drug alone, even when each was administered only once monthly.     

Antistaphylococcal activity of rifampin with other antibiotics

The bactericidal activity of rifampin plus other antibiotics was examined with in vitro checkerboard dilutions against 15 strains of staphylococci, with time-kill studies, and with determinations of serum bactericidal activities (SBAs) in volunteers. In vitro synergism was found consistently only in inhibitory assays with rifampin plus minocycline. Time-kill studies with rifampin plus methicillin revealed enhanced killing at concentrations close to the MBC but reduced combined activity at higher concentrations. SBAs with rifampin, oxacillin, and the two drugs in combination were studied in three treatment regimens (regimen A: 2 g of oxacillin and 300 mg of rifampin; regimen B: 1 g of oxacillin and 450 mg of rifampin; and regimen C: 3 g of oxacillin and 450 mg of rifampin). The SBA against methicillin-sensitive Staphylococcus aureus was significantly lower with the two drugs in combination than with oxacillin alone in regimen A but not in regimen B. In vitro synergy with rifampin plus other antibiotics was not frequent. At high concentrations, the bactericidal activity of oxacillin was reduced by rifampin, but killing activity may be enhanced at low concentrations of oxacillin.     

Fosmidomycin-clindamycin for Plasmodium falciparum Infections in African children

BACKGROUND: Fosmidomycin is a new antimalarial drug with a novel mechanism of action. Studies in Africa that have evaluated fosmidomycin as monotherapeutic agent demonstrated its excellent tolerance, but 3-times-daily treatment regimens of >or=4 days were required to achieve radical cure, prompting further research to identify and validate a suitable combination partner to enhance its efficacy. METHODS: We conducted a randomized, controlled, open-label study to evaluate the efficacy and safety of fosmidomycin combined with clindamycin (n=12; 30 and 5 mg/kg body weight every 12 h for 5 days, respectively), compared with fosmidomycin alone (n=12; 30 mg/kg body weight every 12 h for 5 days) and clindamycin alone (n=12; 5 mg/kg body weight every 12 h for 5 days) for the clearance of asymptomatic Plasmodium falciparum infections in schoolchildren in Gabon aged 7-14 years. RESULTS: Asexual parasites were rapidly cleared in children treated with fosmidomycin-clindamycin (median time, 18 h) and fosmidomycin alone (25 h) but slowly in children treated with clindamycin alone (71 h; P=.004). However, only treatment with fosmidomycin-clindamycin or clindamycin alone led to the radical elimination of asexual parasites as measured by day 14 and 28 cure rates of 100%. Asexual parasites reappeared by day 28 in 7 children who received fosmidomycin (day 14 cure rate, 92% [11/12; day 28 cure rate, 42% [5/12]). All regimens were well tolerated, and no serious adverse events occurred. CONCLUSION: The combination of fosmidomycin and clindamycin is well tolerated and superior to either agent on its own with respect to the rapid and radical clearance of P. falciparum infections in African children.     

Enhanced treatment of Lassa fever by immune plasma combined with ribavirin in cynomolgus monkeys

Lassa virus-infected cynomolgus monkeys were treated with Lassa virus-immune monkey serum containing a high concentration of neutralizing antibody, the antiviral drug ribavirin, or a combination of ribavirin plus immune serum at various times after infection. When treatment was initiated early (day 0 or 4), either ribavirin (30 mg/kg of body weight per day) or immune serum alone protected monkeys. However, when the initial treatment was delayed until day 7, only four of eight ribavirin-treated and only one of six serum-treated monkeys survived. Treatment with ribavirin combined with immune serum was more successful; all infected monkeys given combination treatment survived, including six treated initially on day 10. Increased doses of ribavirin given alone were toxic. The empirical observation that combined treatment with ribavirin plus serum results in enhanced survival in experimentally infected monkeys suggests that combined treatment might benefit human patients with Lassa fever as well.     

Analysis of 42 cases of septicemia caused by an epidemic strain of methicillin-resistant Staphylococcus aureus: evidence of resistance to vancomycin.

Recent case reports of vancomycin treatment failures in the United States, Japan, and France have prompted a retrospective analysis of 42 cases of septicemia caused by epidemic methicillin-resistant Staphylococcus aureus strain 15 (EMRSA-15), which is the most prevalent epidemic strain of methicillin-resistant S. aureus in the United Kingdom; all cases occurred in a teaching hospital in Manchester, United Kingdom, between 1994 and 1998. Mortality was lowest (4%) in patients with rifampin-susceptible isolates treated with vancomycin and rifampin. It rose to 38% in patients who were treated with both antibiotics but in whom the organism became resistant to rifampin during therapy, and it reached 78% in patients who had rifampin-resistant isolates or in whom rifampin was contraindicated (P<.0001; Fisher exact test, 2-tailed). All isolates were susceptible to vancomycin by conventional laboratory testing, but susceptibility was lost by growth in vancomycin in vitro, becoming resistant at a minimum inhibitory concentration of 8 mg/L. This was associated with accumulation of cell-wall material. The deoxyribonucleic acid fingerprint remained unchanged. This study suggests that rifampin played a key role in the prevention of deaths caused by an epidemic strain of methicillin-resistant S. aureus that readily gave rise to a subpopulation with reduced susceptibility to vancomycin.     

Right-sided Staphylococcus aureus endocarditis in intravenous drug abusers: two-week combination therapy

STUDY OBJECTIVE: To determine the efficacy of short-course combination regimens for selected cases of Staphylococcus aureus endocarditis in intravenous drug abusers. DESIGN: Open study of nafcillin and tobramycin or vancomycin and tobramycin administered for 2 weeks with no further therapy. SETTING: County hospital. PATIENTS: Consecutive sample of 53 intravenous drug abusers with relatively uncomplicated right-sided S. aureus endocarditis, defined by clinical and echocardiographic criteria, and without renal insufficiency, extrapulmonary metastatic infectious complications requiring prolonged therapy or surgery for cure, meningitis, methicillin-resistant organism, aortic or mitral valve involvement, or pregnancy. INTERVENTIONS: Nafcillin, 1.5 g intravenously every 4 hours, plus tobramycin, 1 mg/kg body weight intravenously every 8 hours, administered for 2 weeks. Vancomycin, 30 mg/kg per day intravenously, in two or three divided doses, was used instead of nafcillin for patients allergic to penicillin. MEASUREMENTS AND MAIN RESULTS: Forty-seven of 50 patients (94%; 95% CI, 87 to 99+) treated with the nafcillin and tobramycin combination were cured. Only 1 of 3 patients treated with vancomycin plus tobramycin (33%, 95% CI, 2 to 86) was cured. CONCLUSIONS: Selected patients with S. aureus endocarditis can be treated safely and effectively with a 2-week course of nafcillin plus tobramycin. Only one of three patients treated with vancomycin plus tobramycin was cured, but three patients are too few to define with confidence the efficacy of this regimen.     

PCR技术监测大蒜素及其与复方磺胺甲基异噁唑伍用治疗小鼠弓形虫病的研究

目的用聚合酶链反应(PCR)评价大蒜素及其与复方磺胺甲基异噁唑(SMZco)伍用治疗小鼠弓形虫病的疗效。方法昆明系小鼠147只,以2×10~4RH株弓形虫速殖子感染后随机分成5组,每组35只。A组和B组为大蒜素与SMZco联合用药组:其中A组两药用至7d后停用SMZco,大蒜素继续用至21d;B组两药用至14d后停用SMZ-co,大蒜素继续用至21d;C组为大蒜素单药组连续用药21d;D组为SMZco单药组连续用药7d;E组7只小鼠为未用药对照组。剂量;SMZco400mg/kg每天1次,大蒜素35mg/kg每天1次。于感染后5、10、15、20、25、30、40和50d从各组随机取3只小鼠,眼眶取血以及取肝实质组织分别提取DNA,PCR检测各组疗效。从各治疗组随机取9只小鼠观察其治疗后存活情况。结果实验小鼠感染后5d血样,除大蒜素组有特异性194bp带,其余各组均未见扩增带。感染后10d到观察结束,均未见特异性扩增带。感染后5d到50d,所有肝组织标本均有特异带,感染后5d扩增带较亮,治疗结束后到观察终止,扩增带较弱。分析结果表明,小鼠存活率,联合用药的A组为77.8％,B组为88.9％;C组小鼠在急性期即很快死亡;D组为44.4％。结论大蒜素与SMZco联合应用治疗弓形虫病具有协同作用,大蒜素单药治疗作用不明显,PCR技术可用于监测疗效及检测弓形虫隐性感染状态。