John L. Brusch

Infective Endocarditis in the U.S., 1998–2009: A Nationwide Study

Background Previous studies based on local case series estimated the annual incidence of endocarditis in the U.S. at about 4 per 100,000 population. Small-scale studies elsewhere have reported similar incidence rates. However, no nationally-representative population-based studies have verified these estimates. Methods and Findings Using the 1998–2009 Nationwide Inpatient Sample, which provides diagnoses from about 8 million U.S. hospitalizations annually, we examined endocarditis hospitalizations, bacteriology, co-morbidities, outcomes and costs. Hospital admissions for endocarditis rose from 25,511 in 1998 to 38, 976 in 2009 (12.7 per 100,000 population in 2009). The age-adjusted endocarditis admission rate increased 2.4% annually. The proportion of patients with intra-cardiac devices rose from 13.3% to 18.9%, while the share with drug use and/or HIV fell. Mortality remained stable at about 14.5%, as did cardiac valve replacement (9.6%). Other serious complications increased; 13.3% of patients in 2009 suffered a stroke or CNS infection, and 5.5% suffered myocardial infarction. Amongst cases with identified pathogens, Staphylococcus aureus was the most common, increasing from 37.6% in 1998 to 49.3% in 2009, 53.3% of which were MRSA. Streptococci were mentioned in 24.7% of cases, gram-negatives in 5.6% and Candida species in 1.0%. We detected no inflection in hospitalization rates after changes in prophylaxis recommendations in 2007. Mean age rose from 58.6 to 60.8 years; elderly patients suffered higher rates of myocardial infarction and death, but slightly lower rates of Staphylococcus aureus infections and neurologic complications. Our study relied on clinically diagnosed cases of endocarditis that may not meet strict criteria. Moreover, since some patients are discharged and readmitted during a single episode of endocarditis, our hospitalization figures probably slightly overstate the true incidence of this illness. Conclusions Endocarditis is more common in the U.S. than previously believed, and is steadily increasing. Preventive efforts should focus on device-associated and health-care-associated infections.

Bactericidal Activity and Pharmacology of Cefazolin

The in vitro bactericidal activity of cefazolin was found to be similar to that of cephaloridine and cephalothin but slightly greater than that of cephalexin against a majority of 233 strains of gram-positive and gram-negative organisms. Cefazolin, however, was two- to eightfold more active than the other two drugs against Escherichia coli and klebsiella. The mean peak concentrations in the serum in 10 normal subjects 1 h after intramuscular injections of 1,000, 500, and 250 mg of cefazolin were 38.8, 18.6, and 12.2 μg/ml, respectively. The antibiotic could still be detected at 8 h. Peak values for a given dose of cephaloridine were comparable. However, blood levels of cefazolin were regularly higher than those of cephaloridine over the first 8 h. The mean half-life of cefazolin in the serum was 2 h, whereas that of cephaloridine was 1.4 h. The degree of serum protein-binding was strikingly higher for cefazolin (81%) than for cephaloridine (24%), suggesting that the antibacterial activity of the former in serum might be less than that of cephaloridine after equal doses. This proved to be the case when the bacterial activity of blood drawn 1, 4, and 8 h after injection of the two drugs was examined.

Cross-Resistance of Pseudomonas to Gentamicin and Tobramycin

Clinical isolates of gentamicin-resistant organisms were found to be resistant to tobramycin, a new aminoglycoside antibiotic.

A PILOT STUDY OF ANTIBIOTIC CYCLING IN THE COMMUNITY HOSPITAL SETTING

OBJECTIVE To assess the feasibility of a quarterly antibiotic cycling program at two community hospitals and to evaluate its safety and impact on antibiotic use, expenditures, and resistance. DESIGN Nonrandomized, longitudinal cohort study. SETTING Two community hospitals, one teaching and one non-teaching. PATIENTS Adult medical and surgical inpatients requiring empiric antibiotic therapy. INTERVENTION We developed and implemented a treatment protocol for the empiric therapy of common infections. Between July 2000 and June 2002, antibiotics were cycled quarterly; quinolones, beta-lactam-inhibitor combinations, and cephalosporins were used. Protocol adherence, adverse drug events, nosocomial infections, antibiotic use and expenditures, resistance among clinical isolates, and length of stay were assessed during eight quarters. RESULTS Physicians adhered to the protocol for more than 96% of 2,494 eligible patients. No increases in nosocomial infections or adverse drug events were attributed to the cycling protocol. Antibiotic acquisition costs increased 31%; there was a 14.7% increase in antibiotic use. Length of stay declined by 1 day. Quarterly variability in the prevalence of vancomycin-resistant enterococci and ceftazidime resistance among combined gram-negative organisms were noted. CONCLUSIONS Implementation of an antibiotic cycling program is feasible in a community hospital setting. No adverse safety concerns were identified. Antibiotic cycling was more expensive, partly due to an increase in antibiotic use to optimize initial empiric therapy. Quarterly antibiogram patterns suggested that antibiotic cycling may have impacted resistance, although the small number of isolates precluded statistical analysis. Further assessment of this approach is necessary to determine its relationship to antimicrobial resistance.

An in vitro and pharmacological comparison of amoxicillin and ampicillin.

Abstract:The pharmacokinetics of orally administered amoxicillin and ampicillin were compared in a crossover manner among healthy volunteers. All subjects received four one-week regimens consisting of 500 and 250 mg of amoxicillin, each given every eight hours, and 500 and 250 mg of ampicillin administered every six hours. Blood and urine were assayed for antibiotic activity on the first and eighth day of each drug course. In the 250 mg trial, the peak levels of amoxicillin in serum were twice those of ampicillin (4.3 and 5.6 µg/ml vs 2.4 and 2.8 µg/ml) and were associated with greater retrieval in the urine of the former drug. At the higher dose level, however, the maximum concentrations in blood of amoxicillin (7.8 and 7.6 µg/ml) were not significantly greater than those of ampicillin (5.9 and 6.3 µg/ml). In addition, their rates of urinary recovery were similar. The antibacterial spectra of the two are found to be quite alike in their marked in vitro activity against strains of penicillin G-sensitive S. aureus, Streptococcus pyogenes, D. pneumoniae, H. influenzae, Salmonella, P. mirabilis, N. gonorrheae and enterococci. Isolates of Klebsiella, indole-positive Proteus species, enterobacter and penicillinase-producing S. aureus were highly resistant to both compounds.

Cardiac infections in the immunosuppressed patient.

This article presents the various manifestations of cardiac infections found in the immunosuppressed host. Emphasis is placed on the correlation between specific impairments of host defenses and the occurrence of certain types of pathogens. The effect of immunosuppression on the clinical manifestations of these infections is discussed. Finally, appropriate diagnostic modalities are presented for the major types of infections.

Bactericidal activity and pharmacology of flucloxacillin

Flucloxacillin, a recent addition to the group of isoxazolyl penicillins, was studied in vitro and in normal volunteers. The bactericidal activity of the drug against most strains of gram-positive bacteria including penicillin-resistant Staphylococcus aureus was similar to that of oxacillin and approximately fourfold greater than that of cloxacillin. Each of the three penicillins was administered orally to a group of ten volunteers for eight days in a dose of 500 mg four times a day. The mean concentrations of flucloxacillin in the serum were two- to sixfold higher than those of the other two agents on the first, fourth and eighth days of therapy. The percentage of flucloxacillin bound by serum protein was 94.6 per cent; for cloxacillin and oxacillin the values were 93.5 and 91.5 per cent, respectively. Using these data, the concentrations of free flucloxacillin in serum were found to be twice as high as those of cloxacillin and oxacillin. These findings suggest that, when administered orally, this new agent may offer some therapeutic advantage over oxacillin and cloxacillin.

Significant Reduction in the Incidence of Phlebitis with Buffered Versus Unbuffered Cephalothin

Cephalothin (1 g every 2 h), buffered cephalothin, and diluent alone (5% dextrose in water) were each administered for 4 days intravenously to 12 volunteers in a double-blind crossover study. The incidence of phlebitis with buffered cephalothin was significantly lower than that with unbuffered drug (P < 0.01) and almost identical to the incidence with diluent alone.

Effect of Probenecid on Penetration of Oxacillin into Fibrin Clots In Vitro

Probenecid significantly enhanced the in vitro penetration of oxacillin into fibrin clots suspended in rabbit serum or normal saline.

Effect of Diuretics on Urinary Excretion of Cephalothin in Humans

Diuretics and antibiotics are frequently used concomitantly. The possibility of drug interactions led us to study the effects of several diuretics on the renal elimination of cephalothin. Five healthy volunteers received a constant infusion of 500 mg of sodium cephalothin per h for 9 h on 4 consecutive days. Each day, after the third hour of infusion, the subjects were given one of the following in varying order: (i) furosemide (1 mg/kg, intravenous), (ii) mercaptomerin (250 mg, intramuscular), (iii) mannitol (25 g, intravenous), or (iv) no diuretic (control day). Fluid losses were replaced hourly. Serum and complete urine collections were obtained each hour and assayed for creatinine and cephalothin (bioassay). Clearances (milliliter per minute) and urinary excretions (milligram per hour) of cephalothin did not differ either when the diuretic day values were compared with control day, or when pre- and postdiuretic results on the same day were compared. Creatinine clearances were not affected by diuretics except for a transient rise after furosemide.