Over a 19-month period, 165 patients with 183 infections caused by community-acquired, methicillin-resistant Staphylococcus aureus were seen at Henry Ford Hospital in Detroit, Michigan. The proportion of community-acquired staphylococcal infections resistant to methicillin rose from 3 % in March 1980 to 38% in September 1981. Drug abuse, serious underlying illness, previous antimicrobial therapy, and previous hospitalization were all associated with the development of this infection. Concurrent with the community epidemic was a nosocomial epidemic of methicillin-resistant S. aureus infection, which accounted for 30.6% of all nosocomial staphylococcal infections in January 1981. Control measures that included isolation, discharge precautions for carriers, and eradication of employee carriage were effective in preventing nosocomial transmission. The prevalence of methicillin-resistant S. aureus carriage among employees was 0.7%. Methicillin-resistant S. aureus may originate in the community as well as in the hospital, and presents a threat to patients in both settings.
We evaluated the in vitro susceptibility of Legionella pneumophila ATCC 33152 (serogroup I) to 13 antibiotics alone and in combination with rifampin (0.1 mg/liter) by three methods. Extracellular susceptibility was determined by MIC determinations and time kill curves in buffered yeast extract broth, while intracellular susceptibility was determined by peripheral human monocytes in RPMI 1640 culture medium. Antibiotic concentrations equal to or greater than the broth dilution MIC inhibited or killed L. pneumophila by-the time kill method, except this was not the case for trimethoprim-sulfamethoxazole. Antibiotic concentrations below the broth dilution MIC did not inhibit Legionella growth. The only antibiotic-rifampin combinations which produced improved killing of L. pneumophila by the time kill method were those in which the logarithmic growth of L. pneumophila occurred during the experiment (rosoxacin, amifloxacin, cinoxacin, trimethoprimsulfamethoxazole, clindamycin, and doxycycline). Neither direct MICs nor time kill curve assays accurately predicted intracellular L. pneumophila susceptibility. Rifampin, erythromycin, ciprofloxacin, rosoxacin, enoxacin, amifloxacin, gentamicin, clindamycin, and doxycycline all inhibited intracellular L. pneumophila growth at readily achievable concentrations in serum. Cefoxitin and thienamycin showed no inhibition of growth, although they were present extracellularly at concentrations that were 20 to 1,000 times their broth dilution MICs. Clindamycin was the only antibiotic that was able to inhibit intracellular L. pneumophila growth at an extracellular concentration below its MIC. The gentamicin (5 mg/liter)-rifampin combination was the only antibiotic-rifampin combination which demonstrated decreased cell-associated Legionella survival in this model of in vitro susceptibility.
Previous studies have shown that metronidazole is an effective chemotherapeutic agent in the treatment of certain types of periodontal disease. The purpose of this study was to assess, over 18 hours, the concentration of the drug in serum and gingival crevicular fluid after a single oral dose. Six female volunteers with gingivitis created by cessation of brushing for 2 weeks, took 250 mg of metronidazole orally. Micropipettes were used to collect 20 μl of serum and 4 to 5 μl of gingival fluid hourly for 8 hours, and at the 12th and 18th hours. Samples were assayed with a high pressure liquid Chromatograph. Mean drug levels in serum closely matched those reported by Stephen et al. (Br Dent Jl: 313, 1966) with polography. Mean serum drug levels peaked at 6.09 μg/ml at the 2nd hour, and mean gingival crevicular fluid drug levels peaked at 3.62 μg/ml at the 2nd and 7th hours. The drug was detectable in both fluids for up to 18 hours. Mean serum concentrations remained greater than mean gingival fluid concentrations at all time intervals, though the differences were not significant (P < 0.05) as determined by a Hotelings' T2 test. Using reported minimal inhibitory concentration values of metronidazole for various periodontopathogens, it was concluded that a single oral dose of metronidazole will deliver potentially inhibitory levels of the drug to the periodontium in serum and in gingival crevicular fluid.
Cefazolin, a new cephalosporin derivative, was studied in the treatment of 105 hospitalized patients with a variety of infections including endocarditis, pneumonia, and urinary and soft tissue infections, and was found to be effective in 104 patients. Cefazolin was also tested in vitro and shown to be effective against staphylococci, pneumococci, Escherichia coli, Klebsiella sp., and Proteus mirabilis by agar dilution method. It was shown to produce high serum levels when administered in a 250-to 1,000-mg intramuscular dose and was well tolerated and free from renal toxicity. Comparison of the results of this study with those from our prior studies on cephaloridine revealed equivalent antibiotic potency, good tolerance to both the agents when given intramuscularly, superior, average blood levels with cefazolin, equal clinical efficacy, and absence of renal toxicity with cefazolin (unlike cephaloridine). Similarly, the results of treatment of pneumococcal pneumonia with intramuscular cefazolin were found to be superior to those for oral cephalexin.Cefazolin is a new (available for study in the United States in 1972) parenteral cephalosporin derivative of 7-aminocephalosporanic acid shown in Japanese studies to be well tolerated and free from renal toxicity (19,20
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