Donald J. Pohlod

Methicillin-resistant Staphylococcus aureus. epidemiologic observations during a community-acquired outbreak

Infection with strains of methicillin-resistant Staphylococcus aureus occurred in 40 patients at time of admission to a large urban hospital from March to December 1980. Community-acquired methicillin-resistant S. aureus infections occurred in 24 drug abusers and 16 nonabusers. Patients with infections had a longer mean hospitalization and previously had received antimicrobial therapy more frequently than control subjects. Drug abusers with infections had been treated with cephalosporins more often than control subjects (P less than 0.05). Phage typing of 32 isolates showed that 21 were linked by a common phage type (29/52/80/95). Transmission of methicillin-resistant S. aureus from community-acquired cases occurred in the hospital. By January 1981, methicillin-resistant S. aureus accounted for 30.6% of nosocomial S. aureus infections at Henry Ford Hospital. Methicillin-resistant S. aureus infection may arise in the community as well as in the hospital and has the potential to disseminate in both settings.

Community-Acquired Methicillin-Resistant Staphylococcus aureus Infections: A New Source for Nosocomial Outbreaks

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.

An Outbreak of Gentamicin-Resistant Klebsiella pneumoniae: Analysis of Control Measures

In April 1978, a strain of gentamicin-resistant Klebsiella pneumoniae (GRK) was introduced into the neonatal intensive care unit of Henry Ford Hospital. An additional ten cases of GRK occurred over the subsequent 16 months and intestinal colonization occurred in up to 91% of admissions per month. All GRK were susceptible to amikacin and were capsular serotype 19. Though hand contamination of hospital personnel with GRK was documented, increased handwashing practices did not reduce colonization rates of neonates with the epidemic strain. Intestinal carriage persisted for up to ten months and could not be eradicated by administering oral colistin sulfate. Discontinuation of gentamicin and utilization of amikacin were associated with a significant reduction in colonization with GRK (p less than 0.05). However, the only control measure that prevented both new cases and colonization with the epidemic strain was the utilization of a strict cohort system.

Effect of Renal Failure and Dialysis on the Serum Concentration of the Aminoglycoside Amikacin

Serum and dialysate levels of amikacin were determined at appropriate intervals after a 300-mg intravenous dose as a continuous infusion in six patients with end-stage renal failure undergoing hemodialysis and in three patients on peritoneal dialysis. The mean serum half-life of amikacin was 3.75 h during (or after) hemodialysis and 29 h during (or after) peritoneal dialysis. Although not on hemodialysis in the same six patients, the serum half-life was 28 h. The results indicate that the maintenance dose of amikacin should be markedly decreased in patients with severe renal failure even if they are treated with peritoneal dialysis, and that serial serum antibiotic concentrations are essential to prevent cumulative toxicity of the drug.

Clinical Studies of Cefazolin and Comparison with Other Cephalosporins

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.

Health care worker exposure to HIV-1 and HTLV I-II in critically Ill, resuscitated emergency department patients

STUDY OBJECTIVE Exposure to HIV-1 is of profound concern to health care workers. HTLV-I and HTLV-II, retroviruses with similar modes of transmission as HIV-1, also cause disease in human beings. Emergency department resuscitations are high-risk situations for such exposure. The purpose was to determine the seroprevalence of HIV-1 and HTLV I-II in patients undergoing ED resuscitations, the magnitude of health care worker exposure, and risk factors associated with infection. DESIGN Prospective identity-unlinked seroepidemiologic study. SETTING ED of a 950-bed private inner-city teaching hospital. Participants included 370 patients undergoing ED resuscitations. MEASUREMENTS Serum was tested for antibodies to HIV-1 and HTLV I-II. Questionnaires were completed by the physician in charge of the ED resuscitations. RESULTS Fifteen (4.1%) (95% confidence interval [CI], 2.1% to 6.1%) patients were HIV-1 seropositive, and seven (1.9%) (95% CI, 0.7% to 3.1%) were HTLV I-II positive. Eleven (5.6%) (95% CI, 2.4% to 8.8%) of 197 trauma patients and 11 (6.4%) (95% CI, 2.8% to 10.0%) of 173 medical patients were infected with one of these viruses. Health care workers had direct cutaneous contact with patient blood during 114 (31%) ED resuscitations and with infected patient blood during 11 (3%) ED resuscitations. An additional 11 ED resuscitations involved parenteral exposures, one to HIV-1-infected blood. No factors could be identified that would quickly and reliably predict infection. CONCLUSION Health care workers must protect themselves in such high-risk situations by strict compliance to mandatory universal precautions.

Single-dose cephalexin therapy for acute bacterial urinary tract infections and acute urethral syndrome with bladder bacteriuria.

The efficacy of single-dose therapy with 3 g of cephalexin was evaluated in 129 women with symptoms of acute uncomplicated lower urinary tract infections. Of 91 patients with significant bacteriuria, 61 (67%) were cured of their original infection; this was similar to the 54 to 79% cure rates reported in unselected populations of women of a wide age range treated for acute uncomplicated urinary tract infections with a single dose of amoxicillin or trimethoprim-sulfamethoxazole (J. Rosenstock, L. P. Smith, M. Gurney, K. Lee, W. G. Weinberg, J. N. Longfield, W. B. Tauber, and W. W. Karney, Antimicrob. Agents Chemother. 27:652-654, 1985; N. E. Tolkoff-Rubin, M. E. Wilson, P. Zuromskis, I. Jacoby, A. R. Martin, and R. H. Rubin, Antimicrob. Agents Chemother. 25:626-629, 1984). The cure rates of (87%) for our younger patients, those less than 25 years of age, was better than that (46%) for our patients over 40 years of age (P less than 0.001). Patients with infections that were negative in an antibody-coated bacteria test were cured at a significantly higher rate than those with infections that were positive in an antibody-coated bacteria test (71 versus 19%; P = 0.003). Those patients with infections caused by cephalexin-susceptible organisms were cured at a rate similar to that for patients with infections caused by cephalexin-resistant organisms (68 versus 50%; P = 0.62). The cure rate for suburban patients was 90%, versus 45% for inner-city patients (P = 0.008). Of the 28 women with acute urethral syndrome due to low-level bacteriuria, 27 were cured.

Ceforanide: In Vitro and Clinical Evaluation

Ceforanide, a new cephalosporin antibiotic with a long half-life (3 h), can be administered twice daily. We evaluated its antimicrobial activity, pharmacology, and clinical efficacy. Twenty-seven patients with infections due to susceptible organisms received ceforanide, 0.5, 1, or 2 g, intramuscularly or intravenously every 12 h for 6 to 28 days. In vitro studies with the clinical isolates from 27 patients treated plus 263 additional isolates showed that ceforanide was active against cephalothin-susceptible gram-positive and gram-negative microorganisms. In addition, ceforanide inhibited 65% of cephalothin-resistant Escherichia coli and 65% of Enterobacter spp. at ≤12.5 μg/ml. After a single 1-g intramuscular dose, the mean peak plasma concentration at 1 h was 48.9 μg/ml and that at 12 h was 4.7 μg/ml. Plasma accumulation occurred in some patients. The infections included 10 pneumonias, 3 with bacteremia and 1 with empyema; 11 soft tissue infections, 4 with abscesses and 3 with sepsis; and 3 urinary tract infections. One case each of endocarditis, osteomyelitis, and septic thrombophlebitis, all due to Staphylococcus aureus, were treated. Clinical response was satisfactory in all patients; bacteriological response was satisfactory in 26 of 27 patients. Ceforanide was well tolerated. Three patients developed mild increases in liver enzymes, and one developed slight eosinophilia. In another case, the antibiotic was discontinued because of a fivefold rise in serum glutamic-oxalacetic transaminase (aspartate aminotransferase) and serum glutamic-pyruvic transaminase (alanine aminotransferase) and a twofold rise in lactic acid dehydrogenase and alkaline phosphatase.

Failure of probenecid to alter the pharmacokinetics of ceforanide.

This investigation evaluated the effect of probenecid on ceforanide concentrations in eight healthy volunteers. Each volunteer was given 1 or 2 g of ceforanide either alone or with 1 g of probenecid. Concentrations of ceforanide in plasma, urine, and saliva were then measured. Probenecid did not alter the plasma concentrations of ceforanide, nor did it affect the urinary excretion of this agent. Ceforanide was not secreted into saliva in any detectable amount either when administered alone or with probenecid. It is not clear why probenecid has a negligible effect on ceforanide concentrations in plasma. It may be that tubular secretion plays less of a role in the excretion of ceforanide than expected, or that the physical properties of ceforanide prevent probenecid from affecting its excretion.

Effect of clavulanic acid on minimal inhibitory concentrations of 16 antimicrobial agents tested against Legionella pneumophila.

A total of 15 Legionella pneumophilia isolated were tested against 16 antimicrobial agents used singly and in combination with clavulanic acid. When combined with clavulanic acid, 4 of the 16 antimicrobial agents produced no enhanced effect. However, the minimal inhibitory concentrations of 12 of the antimicrobial agents were reduced by one-half to one-third when in combination with clavulanic acid. These reductions reflected only a one-dilution decrease, however, in the original minimal inhibitory concentrations. Thus, clavulanic acid combinations appear to be only nominally effective beta-lactamase inhibitors against L. pneumophilia.