Richard Quintiliani

Experience with a once-daily aminoglycoside program administered to 2,184 adult patients.

Once-daily aminoglycoside (ODA) regimens have been instituted to maximize bacterial killing by optimizing the peak concentration/MIC ratio and to reduce the potential for toxicity. We initiated an ODA program at our institution that utilizes a fixed 7-mg/kg intravenous dose with a drug administration interval based on estimated creatinine clearance: > or = 60 ml/min every 24 h (q24h), 59 to 40 ml/min q36h, and 39 to 20 ml/min q48h. Subsequent interval adjustments are made by using a single concentration in serum and a nomogram designed for monitoring of ODA therapy. Since initiation of the program, 2,184 patients have received this ODA regimen. The median dose was 450 (range, 200 to 925) mg, while the median length of therapy was 3 (range, 1 to 26) days. The median age of the population was 46 (range, 13 to 97) years. Gentamicin accounted for 94% of the aminoglycoside use, and the majority (77%) of patients received the drug q24h. The 36-, 48-, and > 48-h intervals were used for 15, 6, and 2% of this population, respectively. Three patients exhibited clinically apparent ototoxicity. Twenty-seven patients (1.2%) developed nephrotoxicity (the Hartford Hospital historical rate is approximately 3 to 5%) after a median of 7 (range, 3 to 19) days of therapy. On the basis of a prospective evaluation of 58 patients and follow-up of additional patients via clinician reports, we have noted no apparent alterations in clinical response with our ODA program. This ODA program appears to be clinically effective, reduces the incidence of nephrotoxicity, and provides a cost-effective method for administration of aminoglycosides by reducing ancillary service time and serum aminoglycoside determinations.

Clinical, epidemiologic and bacteriologic observations of an outbreak of methicillin-resistant Staphylococcus aureus at a large community hospital.

Over a 12 month period, 61 isolates of methicillin-resistant Staphylococcus aureus (MR-SA) were obtained in 23 hospitalized patients. Eight-six per cent of the patients were over 50 years of age, and 91 per cent were in the postoperative period. In 10 patients (42 per cent), MR-SA was the major pathogen, producing either pneumonia, empyema, osteomyelitis, lung abscess, enterocolitis, wound infection or bacteremia with sepsis. Three patients in this group died despite therapy with antibiotics with in vitro activity against these organisms. All the patients probably acquired their MR-SA in the hospital, and five carriers of the organism were identified among hospital personnel. This outbreak demonstrates the ability of MR-SA not only to colonize many patients in a relatively brief period of time, but also to produce serious disease.

The Pharmacodynamics of Aminoglycosides

Recently, a more complete understanding of the pharmacodynamics of aminoglycosides has been recognized, indicating that this class of antibiotics exhibits both concentration-dependent bactericidal activity and a postantibiotic effect. This pharmacodynamic information, along with better knowledge of the mechanisms responsible for aminoglycoside toxicity, established the foundation for once-daily aminoglycoside dosing regimens. This new approach to aminoglycoside dosing appears to be safe, efficacious, and cost-effective, resulting in its increasing popularity in clinical practice.

Continuous versus intermittent administration of ceftazidime in intensive care unit patients with nosocomial pneumonia

A prospective, randomized pilot study was undertaken to compare the efficacy of continuous versus intermittent ceftazidime in ICU patients with nosocomial pneumonia. Ceftazidime was administered either as a 3 g/day continuous infusion (CI) or an intermittent infusion (II) of 2 g every 8 h. In addition, all patients received concomitant once-daily tobramycin. The demographics of the evaluable patients (n = 35) were similar between the groups: age (years), CI 46 +/- 16, II 56 +/- 20; Apache score, CI 14 +/- 4, II 16 +/- 6; time (days) from admission to diagnosis, CI 9 +/- 6, II 9 +/- 6. Clinical efficacy, defined as cure/improvement was similar between groups [n (%), CI 16/17 (94), II 15/18 (83)], while microbiological response was also comparable [n (%), CI 10/13 (76), II 12/15 (80)]. Minimal inhibitory concentrations (MICs) for all isolates were measured throughout the treatment course; there was no development of resistance during therapy for either regimen. While limited clinical data exist, our results suggest that the use of ceftazidime by CI administration maintains clinical efficacy, optimizes the pharmacodynamic profile and uses less antibiotic compared with the standard 2 g every 8 h intermittent dosing regimen.

Clinical efficacy and pharmacoeconomics of a continuous-infusion piperacillin-tazobactam program in a large community teaching hospital.

Study Objective. To compare continuous versus intermittent administration of piperacillin‐tazobactam with regard to clinical, microbiologic, and economic outcomes.

Gram-negative bacillary meningitis☆

All cases of unusual types of gram-negative bacillary meningitis in a university hospital over a five year period were retrospectively analyzed. These patients comprised 4.2 per cent of cases of bacterial meningitis among all patients, 69 per cent of neurosurgical cases and 42 per cent of neonatal cases. The over-all mortality was 40.3 per cent. The two most common bacterial isolates were Escherichia coli in patients younger than one year and Klebsiella species in patients above that age. Infection may be acquired at birth or at the time of surgery, or may be secondary to spread of infection from other body sites. Gram-negative bacillary meningitis is a nosocomial infection and this diagnosis should be suspected in patients in whom central nervous system infection develops in the hospital.

Trimethoprim-Sulfamethoxazole for Bacterial Meningitis

Trimethoprim-sulfamethoxazole has excellent microbiologic activity against most pathogens that produce meningitis; both components of this drug have high penetration into tissues, including the cerebrospinal fluid. Clinical experience shows that trimethoprim-sulfamethoxazole may be beneficial in the treatment of gram-negative bacillary meningitis caused by organisms only moderately susceptible to third-generation cephalosporins (Enterobacter cloacae, Serratia marcescens) or resistant to these antibiotic agents (Pseudomonas cepacia, Acinetobacter). The success of trimethoprim-sulfamethoxazole in the treatment of four patients with Staphylococcus aureus and two patients with Listeria monocytogenes meningitis shows that this drug may also be useful in treating infrequent types of gram-positive meningitis.

Vancomycin Therapeutic Drug Monitoring: Is it Necessary?

OBJECTIVE: To review the literature and assess the validity of obtaining vancomycin serum drug concentrations in patients. DATA SOURCES: A MEDLINE search of the English literature and a bibliographic review of articles pertaining to vancomycin serum concentrations, their use, and the rationale of cited therapeutic ranges. STUDY SELECTION AND DATA EXTRACTION: Studies pertaining to the use of vancomycin concentrations in the clinical setting, methods for predicting these concentrations, and studies that reported efficacy or toxicity associated with vancomycin use and possible correlation of serum concentrations. DATA SYNTHESIS: The usefulness of vancomycin serum concentrations, the determination of a therapeutic range of values, and their correlation to antibacterial efficacy and drug toxicity in the clinical setting are controversial. Old reports of toxicities need to be critically examined due to lack of information and the actual frequency of toxic reactions. The efficacy of vancomycins antibacterial effect and its correlation with reported therapeutic ranges may advocate obtaining a vancomycin trough concentration in certain groups of patients. CONCLUSIONS: Determination of serum vancomycin concentrations in the clinical setting and their usefulness in patient care is questionable and unnecessary in the majority of patients.

The penetration characteristics of cefazolin, cephalothin, and cephradine into bone in patients undergoing total hip replacement.

Preoperatively, to prevent infection, seventy-one patients who were to have total hip arthroplasty were given one gram of cephalothin, cephradine, or cefazolin intravenously. Simultaneous samples of bone and serum were obtained after various time intervals and assayed for cephalosporin concentration to correlate the antibiotic concentrations in these sites with time. Of the cephalosporins tested, cefazolin achieved the highest total peak levels in bone (thirty micrograms per gram), followed in descending order by cephradine (twenty-three micrograms per gram) and cephalothin (2.8 micrograms per gram). These peak levels in bone, reached twenty-five to forty minutes after injection, were sixty, 6.7, and fifteen times higher than the usual mean minimum inhibitory concentrations of cefazolin, cephradine, and cephalothin, respectively, for penicillin-resistant staphylococci. The half-lives of the antibiotics in bone were forty-two, forty, and thirty minutes, respectively.

Development of Meningitis During Cephalothin Therapy

Abstract Five patients developed meningitis while receiving cephalothin. Three other cases of this complication have been previously reported. Patients with bacteremia and debilitating chronic dise...