Antibiotic use in the critical care unit.

The antimicrobial management of patients in the critical care unit is complex. Not only must the clinician be familiar with a number of clinical, microbiological, pharmacological, and epidemiological observations but also fundamental pharmacodynamic concepts. It is an understanding of these concepts that forms the basis for the design of dosing strategies that maximize clinical efficacy and minimize toxicity. Antimicrobial selection is further complicated by the plethora of new antimicrobial agents available with varying clinical utility. Nowhere is this more evident than in the quinolone class of antibiotics. To aid the clinician in differentiating between quinolones it now seems reasonable to create a classification system akin to the generation grouping applied to the cephalosporins. Our classification is based upon the pharmacodynamic principles discussed within this article.

Rifampin-fluconazole interaction in critically ill patients.

OBJECTIVE: To report the influence of rifampin coadministration on the pharmacokinetics of fluconazole in 2 critically ill patients. CASE SUMMARIES: The pharmacokinetics of fluconazole are reported in 5 patients in the intensive care unit (ICU), 2 of whom received rifampin and 3 who received only fluconazole. Patient 1 was a 52 year-old man with bilateral pneumonia who received rifampin for 9 days in addition to other antibiotics when fluconazole was added for suspected fungal superinfection. Patient 2, a 39-year-old man with steroid-dependent asthma was admitted to the ICU with a right middle lobe pneumonia and ventilatory insufficiency. Because of rapid clinical deterioration, intravenous rifampin 600 mg q12h and fluconazole 100 mg q24h were added to conventional antibacterial therapy. Patients 3-5 received intravenous fluconazole therapy, but were never administered rifampin prior to their antifungal therapy. DISCUSSION: Fluconazole has gained wide use as an antifungal agent because of its efficacy, limited toxicity, and the paucity of reported drug interactions. In some clinical situations, however, the drug must be coadministered with rifampin. Limited data in healthy volunteers suggest that the coadministration of rifampin and fluconazole results in a 23% reduction in the fluconazole area under the concentration-time curve (AUC). In this report, we found a statistically significant lowering of the AUC (52%) and a 93% higher total body clearance of fluconazole in patients treated with rifampin. CONCLUSIONS: Although limited data are available describing the magnitude of the interaction between fluconazole and rifampin in patients, our data suggest a more significant interaction than previously reported. If the concurrent administration of the 2 drugs in unavoidable, the patient's clinical response to treatment should be monitored closely, as the unexpectedly large reduction in fluconazole serum concentrations may lead to poor treatment outcomes.

Antibiotic formulary selection.

Physicians worldwide are being forced to consider economics in the care of patients. In most hospitals, antibiotics are a steadily increasing segment of the pharmacy budget. This article discusses how the authors used drug pharmacokinetics, restriction policies, and cost benefit analysis to design a cost-effective antibiotic formulary.

Rational vancomycin use recommendations.

The increasing occurrence of VRE will dramatically affect the management of infections in hospitalized patients, as well as increase morbidity and mortality. Vancomycin is the therapy of choice for certain gram-positive infections in patients with significant allergic histories to beta-lactam antibiotics and for infections with gram-positive microorganisms that are resistant to beta-lactam antibiotics. Conservative use of vancomycin in the future may help to avoid the further development of resistant organisms.

Comparative virulence of blood and stool isolates of Shigella sonnei.

Shigellemia is rare in developed countries and might result from the emergence of unusually virulent strains. We compared systemic invasiveness markers of isolates from the blood of 3 temporally clustered patients with Shigella sonnei bacteremia in Boston with those of 11 unrelated contemporaneous strains from stools of people in New England. We found no difference between the two groups in O-chain length by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, mouse 50% lethal dose, in vivo response to iron, and susceptibility to serum, which varied from moderately susceptible to ultrasusceptible. Mean intraperitoneal 50% lethal doses of smooth form I colonies for mice were equally low (10(5.8) CFU) in both groups, and the 50% lethal doses were lowered equally further in the two groups by predosing with iron to levels useful in mouse model sepsis studies. S. sonnei bacteremia may reflect compromised host defenses, not bacterial virulence.

Cellulitis due to Streptococcus pneumoniae: case report and review.

Although Streptococcus pneumoniae remains the most common cause of community-acquired bacterial pneumonia, its involvement in skin infection is notably infrequent. A review of the literature uncovered only 13 cases of pneumococcal cellulitis in adults. Distinguishing features of skin infection by S. pneumoniae included the presence of bullae, brawny erythema, and a violaceous hue in the affected skin area. Most patients with pneumococcal cellulitis had chronic illnesses or were immunocompromised because of drug or alcohol abuse. Even with appropriate antimicrobial therapy, many patients required prolonged hospitalizations and surgery for cure. We report a case of primary pneumococcal cellulitis with secondary bacteremia in an alcoholic patient who required extensive surgical therapy and whose course was additionally complicated by acute glomerulonephritis.

Strategic antibiotic decision-making at the formulary level.

The proliferation of antimicrobial agents introduced for the treatment of increasingly complex infectious diseases, coupled with the obligation to provide the best possible medical care in keeping with hospital fiscal constraints, has created a need for strategic decision-making about antibiotics at the formulary level. The following experience at the Hartford Hospital, a 1,000-bed tertiary-care facility, represents an example of an antibiotic management system based on a multidisciplinary approach that utilizes infectious disease physicians, clinical microbiologists, hospital epidemiologists, and pharmacists.

Nosocomial infection in adult patients with sickle cell anemia.

Although the vulnerability of patients with sickle cell disease to infection with encapsulated organisms is well recognized, nosocomial transmission of infection has not been studied in this population. We describe eight serious, nosocomially transmitted infections in four adult patients hospitalized for complications of sickle cell disease, which led to death in one patient and prolonged hospital stays in three others. Although we have not surveyed all patients with sickle cell disease for rates of nosocomial infection, the cases presented suggest that these patients may be at increased risk. Risk can be reduced if health care workers are especially vigilant in adhering to handwashing and other infection control measures when caring for these patients. Additionally, we recommend that a patient with sickle cell disease not share a room with a patient known to have or suspected of having a nosocomial or community-acquired infectious disease.

Nosocomial septicemia with CDC group IV c-2, an unusual gram-negative Bacillus.

A 55-year-old man with severe peripheral vascular disease developed nosocomial septicemia which was caused by the gram-negative bacterium CDC group IV c-2, presumably from a plantar abscess on the left foot. Recovery followed amputation of the infected extremity and antibiotic therapy. This is the first reported case of nosocomial acquisition of this organism.

Invasive Haemophilus influenzae disease in adults.

In a five-year period, 29 cases of bacteremia and/or meningitis in adults caused by Haemophilus influenzae were seen in our large community hospital. There were 17 cases of bacteremic pneumonia and 12 cases of serious extrapulmonary infections. The extrapulmonary infections included cases of endocarditis, meningitis, cholecystitis, epiglottitis, tubo-ovarian abscess, and cellulitis. In contrast with the pediatric experience, H influenzae type B was the causative pathogen in only 45% of patients and only one isolate was ampicillin resistant.