Nosocomial infection caused by antibiotic-resistant organisms in the intensive-care unit.

Resistance to antimicrobial agents is an evolving process, driven by the selective pressure of heavy antibiotic use in individuals living in close proximity to others. The intensive care unit (ICU), crowded with debilitated patients who are receiving broad-spectrum antibiotics and being cared for by busy physicians, nurses, and technicians, serves as an ideal environment for the emergence of antibiotic resistance. Problem pathogens presently include multiply resistant gram-negative bacilli, methicillin-resistant Staphylococcus aureus, and the recently emerged vancomycin-resistant enterococci. The prevention of antimicrobial resistance in ICUs should focus on recognition via routine unit-based surveillance, improved compliance with handwashing and barrier precautions, and antibiotic-use policies tailored to individual units within hospitals.

An outbreak of gram-negative bacteremia traced to contaminated O-rings in reprocessed dialyzers.

OBJECTIVE: To investigate an outbreak of gram-negative bacteremia in an outpatient hemodialysis unit and to identify the source of contaminating bacteria and the route by which bacteria gained access to the bloodstream. DESIGN: A matched-pair, case-control study and a bacteriologic investigation of the hemodialysis unit and the implicated dialyzers. SETTING: A university outpatient hemodialysis unit. PATIENTS: Eleven patients receiving long-term hemodialysis who had a total of 12 episodes of primary gram-negative bacteremia and 12 matched controls. MEASUREMENTS: Clinical and demographic data were obtained for patients and controls. Dialysis unit procedures were observed for compliance with aseptic technique. Cultures of potential environmental sources of bacteria were obtained. Hemodialyzers from bacteremic and nonbacteremic patients were dismantled, and the component parts were cultured. Inoculation of O-rings (from Hemoflow F-80 dialyzer) with bacteria and simulated dialysis were done. RESULTS: During January to October 1988, 12 episodes of primary gram-negative bacteremia caused by Pseudomonas cepacia, Xanthomonas maltophilia, Citrobacter freundii, Acinetobacter calcoaceticus var. anitratus, or Enterobacter cloacae occurred in 11 patients. In 11 episodes, symptoms developed within 3 hours of starting hemodialysis. Intravenous antibiotics were administered for 11 episodes, 3 episodes resulted in hospitalization, and all patients recovered. Case patients were more likely to have received high-flux dialysis with Hemoflow F-80 dialyzers (odds ratio congruent to 11) than were controls. O-rings from dialyzers used by bacteremic patients were culture positive for the organism responsible for bacteremia. Three of the four dialyzers were disinfected using the standard automated method and were recultured 72 hours later; the O-rings of all three dialyzers remained culture positive. Simulated dialysis using dialyzers with contaminated O-rings caused blood pathway contamination despite intervening reprocessing. When the disinfection method for F-80 dialyzers included removal and complete disinfection of the O-rings, O-ring and blood pathway cultures were consistently negative. After this procedure was made routine, no episodes of primary gram-negative bacteremia occurred during the next 6 months. CONCLUSIONS: Because dialyzers with removable headers and O-rings are widely used in patients receiving long-term hemodialysis, disinfection procedures should include measures to ensure adequate disinfection of O-rings.

Microbiological efficacy and pharmacokinetics of prophylactic antibiotics in liver transplant patients.

The pharmacokinetics of perioperative systemic antibiotics and the microbiological effectiveness of oral nonabsorbable antibiotics started immediately prior to surgery were studied in 18 adult patients undergoing liver transplantation. All patients received cefotaxime, 2 g intravenously, at 6-h intervals during surgery and then at 8-h intervals thereafter for 48 h; eight patients also received ampicillin at the same dose and schedule. This regimen produced levels of antibiotics in blood that appeared appropriate for prophylaxis. The first dose peak (68 +/- 18 micrograms/ml) and trough (6.9 +/- 4.7 micrograms/ml) levels of cefotaxime in serum and the first dose peak (73 +/- 22 micrograms/ml) and trough (4.1 +/- 2.3 micrograms/ml) levels of ampicillin in serum, which were assayed by high-performance liquid chromatography, were similar to levels reported in normal volunteers, despite mean intraoperative blood loss of 3.3 liters and fluid replacement of 21 liters. On postoperative days 1 and 2, the levels of cefotaxime and ampicillin were maintained at or above 0.9 and 1.3 micrograms/ml, respectively, with little accumulation. By random assignment, 8 patients received systemic antibiotics alone and 10 patients received systemic antibiotics plus a 3-week regimen of oral nonabsorbable antibiotics (gentamicin, polymyxin E, and nystatin) beginning when a donor liver was procured. Pre- and postoperative cultures of rectum, throat, and gastric aspirate samples showed persistence of aerobic gram-negative bacilli for the first 2 postoperative weeks in about half of the patients in each group. Failure of the regimen of oral nonabsorbable antibiotics to supplement cefotaxime in eradicating aerobic gram-negative bacilli from stools probably results from impaired peristalsis during and after surgery and warrants earlier initiation of the regimen.

Systemic Bacillus species infection mimicking listeriosis of pregnancy.

Bacillus species are increasingly recognized as agents of infection in humans. These organisms are ubiquitous in nature and can cause clinical illness ranging from transient bacteremia to serious systemic infection. We describe a pregnant intravenous drug abuser with fever, constitutional symptoms, and premature labor. Her blood cultures yielded gram-positive bacilli, and her clinical course was consistent with systemic listeriosis of pregnancy. Pathological examination of the placenta revealed acute villitis, and Bacillus species grew from cultures of both placenta and blood. Through biochemical testing the isolate was identified as Bacillus pumilis. To our knowledge, this is the first reported case of premature labor induced by Bacillus species infection.

Septic endarteritis of the femoral artery following angioplasty.

A case of septic endarteritis that occurred in the femoral artery following percutaneous transluminal coronary angioplasty (PTCA) is reported, and nine previously reported cases of this complication are reviewed. In each case Staphylococcus aureus was identified as the pathogen. For all cases in which a complete clinical description was available, endarteritis occurred following repeated PTCA or repuncture PTCA (i.e., a second catheterization at the original site of insertion for diagnostic purposes). The characteristic manifestations of endarteritis in this setting included bacteremia (all 10 cases), the formation of a pseudoaneurysm (six), distal emboli (five), and regional septic arthritis or osteomyelitis (five of six cases that included the information needed to determine the presence of these conditions). In each case, treatment included 4-6 weeks of iv antibiotics and surgery, most frequently resection of the pseudoaneurysm and vascular bypass. We recommend surveillance for the signs of endarteritis, especially after repeated catheterization, and use of the contralateral site when repeated catheterization is indicated. When the ipsilateral site is used, the administration of prophylactic antibiotics should be considered.

Infection control and pneumonia prophylaxis strategies in the intensive care unit.

Conventional infection control approaches, such as dedicated surveillance and control programs and barrier isolation techniques, effectively interrupt acquisition of many pathogens and reduce infection rates in the intensive care unit (ICU). However, a substantial proportion of infections results from endogenous rather than acquired organisms and require that we also develop strategies to prevent the progression from colonization to infection. Studies of systemic antimicrobial prophylaxis for patients at risk for pneumonia have consistently failed to demonstrate benefit. Topical endotracheal prophylaxis succeeded in preventing pneumonia but was complicated by the emergence of intrinsically resistant gram-negative bacilli. More recently, a number of trails have evaluated selective decontamination of the oropharynx and gastrointestinal tract with nonabsorbable antibiotics. These regimens have demonstrated a substantial impact on pneumonia and overall infection rates in ICU patients. Further investigation will define the role of selective decontamination in selected patient populations as well as address concerns over selection of resistance. Other strategies, including immunoprophylaxis, colonization-resistant devices, and methods to decrease bacterial adherence may also prevent progression from colonization to infection and will be the subject of future investigation.

Multicenter, randomized trial of ciprofloxacin plus azlocillin versus ceftazidime plus amikacin for empiric treatment of febrile neutropenic patients.

In a multicenter, randomized clinical trial, the efficacy of ciprofloxacin plus azlocillin was compared with that of a standard regimen of ceftazidime plus amikacin for the initial empiric treatment of fever in neutropenic cancer patients. In addition, the efficacy of early conversion from intravenous therapy to orally administered ciprofloxacin was compared with that of continued ceftazidime plus amikacin. Seventy-one oncology patients with 79 episodes of fever and neutropenia were randomly assigned to receive initial empiric antibiotic therapy with either intravenously administered ciprofloxacin and azlocillin followed by orally administered ciprofloxacin (regimen 1, 25 episodes); ceftazidime and amikacin (regimen 2, 30 episodes); or ceftazidime and amikacin followed by oral ciprofloxacin (regimen 3, 24 episodes). Microbiologically documented infections were the cause of fever in 10 (40 percent), seven (23 percent), and nine (38 percent) episodes in regimens 1, 2, and 3, respectively, including six, five, and four episodes of bacteremia. Patient survival was 90 to 92 percent in each regimen; however, some modification of antimicrobial therapy occurred in 65, 44, and 41 percent of surviving patients in regimens 1, 2, and 3, respectively. The rate of clearance of initial bacteremia was 67 percent (four of six) in regimen 1, 100 percent (five of five) in regimen 2 and 50 percent (two of four) in regimen 3. Patients in regimens 1 and 3 were able to convert to orally administered ciprofloxacin in 32 (65 percent) of 49 episodes after a mean of six days of intravenous therapy. Superinfections occurred in 24, 10, and 12 percent of patients receiving regimens 1, 2, and 3, respectively, and occurred similarly for patients receiving orally administered ciprofloxacin, 12 percent (four of 32), and intravenous therapy, 17 percent (eight of 47). Parenteral ciprofloxacin was generally well tolerated. One (4 percent) of 25 patients receiving regimen 1 experienced oto- or nephrotoxicity, compared with eight (15 percent) of 54 patients receiving regimens 1, 2, and 3 (p = 0.15), including three patients who required premature termination of aminoglycoside therapy. Our data suggest that the combination of ciprofloxacin and azlocillin is an effective alternative to ceftazidime and amikacin for the initial empiric therapy of febrile neutropenic patients, is generally well tolerated, and avoids the oto- and nephrotoxicity associated with aminoglycoside use. In addition, a majority of patients could change to orally administered ciprofloxacin alone after six days of parenteral therapy.