In vitro activity of piperacillin/tazobactam against isolates from patients enrolled in clinical trials.

The in vitro activity of piperacillin alone or titrated with a constant concentration of 4 mug/ml tazobactam was evaluated against 3962 baseline pathogens isolated from 1899 patients enrolled in 9 clinical trial studies in North America. Tazobactam increased susceptibility rates of piperacillin for Enterobacteriaceae from 81% to 96%, Staphylococcus (methicillin susceptible) spp. from 6% to 100%, Bacteroides fragilis group from 79% to >99% and Haemophilus from 85% to 98%. The excellent activity of piperacillin against Pseudomonas, Streptococcus and Enterococcus was maintained in the presence of tazobactam. Overall piperacillin/tazobactam had better activity than ticarcillin/clavulanic acid, ceftazidime, and in general equaled the activity of imipenem. The excellent in vitro, extended-spectrum activity of piperacillin/tazobactam suggests its utility for various infections.

Enhanced virulence of Escherichia coli bearing a site-targeted mutation in the major structural subunit of type 1 fimbriae.

Type 1 fimbriae promote enterobacterial adherence to a variety of mammalian cells and are thought to play an important role in the establishment of various extraintestinal infections. Whether or not this adhesin has a role in the pathogenesis of peritoneal Escherichia coli infections, such as those initiated by bowel leakage during intraabdominal surgery, is unclear. By using two genetically engineered E. coli strains, each bearing an antibiotic resistance element inserted at a different site within the type 1 fimbria operon, we examined the role of type 1 fimbriation in intraperitoneal infection in rats. A permanently nonfimbriated insertion mutant was compared with an analogously constructed normally fimbriated one. After intraperitoneal inoculation of adult rats, the permanently nonfimbriated mutant produced mortality more rapidly and resulted in a greater number of culturable organisms from both the peritoneum and the blood. Moreover, the differences between these two insertion mutants were dramatically enhanced by preinoculation growth conditions favoring fimbrial expression. After growth under these conditions, 10(3) CFU of the fimbriation-proficient strain inoculated intraperitoneally caused no mortality; in sharp contrast, the permanently nonfimbriated insertion mutant resulted in death in 60% of the animals inoculated. Notwithstanding evidence that type 1 fimbriae mediate enterobacterial adherence to mammalian oropharyngeal and bladder mucosae, the results presented here demonstrate that type 1 fimbrial expression can lead to diminution of the number of E. coli organisms within the peritoneum.

Peritonitis into the 1990s: changing pathogens and changing strategies in the critically ill.

To study the effect of severe illness on the nature of peritonitis and intra-abdominal abscesses, the microbiology and clinical course of patients operated on over a 1-year period with culture-proven intra-abdominal infections whose preoperative Acute Physiology and Chronic Health Evaluation (APACHE) II scores were greater than or equal to 15 (predicted mortality at least 50%) were examined. Twenty-nine patients were enrolled, and overall mortality was 52 per cent, with increasing mortality correlating with higher APACHE II scores. The organism most commonly isolated from the peritoneum was Candida albicans, followed by Enterococcus species, Enterobacter species, and Staphylococcus epidermidis. An increase in the mean of the APACHE II scores on Days 3 and 7 compared to the preoperative score was associated with a 91 per cent mortality, while a decrease was associated with only a 22 per cent mortality. The authors conclude that the microbiology of intra-abdominal infections is inherently different in severely ill patients and that longitudinal clinical scoring may be more useful than a single scoring in predicting outcome. These data suggest that trials to investigate the broadening of standard perioperative antimicrobial coverage in the ill and use of longitudinal clinical scoring to direct aggressive reintervention may be warranted.

Preexposure of the peritoneum to live bacteria increases later mixed intraabdominal abscess formation and delays mortality.

Intraabdominal infections are a major source of morbidity and mortality for the trauma and postoperative patient. Transient peritoneal contamination with bacteria after either intentional or unintentional violation of the gut are common. The effect of this intermittent antigen exposure upon later formation of intraabdominal abscesses is unclear. Previous experiments by others have demonstrated that repeated exposure to Bacteroides fragilis capsular polysaccharide can induce a T lymphocyte-mediated immunity to subsequent induction of pure B. fragilis abscess formation. In a murine mixed intraabdominal abscess model, preexposure to live Escherichia coli, B. fragilis, or both increased the number of later abscesses and in some cases their bacterial composition. Further, immunization with E. coli alone increased late mortality without altering overall mortality. These data suggest that the alterations of immune function produced by live, transient bacteria upon subsequent mixed intraabdominal abscess induction result in fundamentally different consequences from those observed after specific polysaccharide antigen exposure and subsequent monomicrobial abscess induction.

The peritoneal environment during infection. The effect of monomicrobial and polymicrobial bacteria on pO2 and pH.

Intraperitoneal (IP) abscesses frequently are composed of aerobes and anaerobes, and, in experimental models, a particulate adjuvant. The environmental changes effected by these components, either singularly or in combination, have not been well defined. The IP pO2, pH, and recoverable bacteria from the peritoneum of rats were quantified over 6 hours during simple aerobic and anaerobic infections and during mixed peritonitis with and without a sterile feces-barium sulfate adjuvant (SFA). Fourteen groups were studied, receiving intraperitoneally, at time of oxygen probe placement, 1 mL normal saline (control), Escherichia coli (EC), Bacteroides fragilis (BF), SFA alone, or a mixture of EC and BF, EC and SFA, BF and SFA, or EC, BF, and SFA. Control animals exhibited a stable IP pO2 and pH during 6 hours. In monomicrobial EC peritonitis, inocula well below the LD50 produced an increased IP pO2 and reduced arterial-peritoneal gradient (APG), with a stable IP pH. By 6 hours lethal doses of EC produced a dramatic decline in IP pO2, with no change in arterial pO2 as well as acidic IP and arterial pHs. Simple BF peritonitis caused no or minor elevations in IP and arterial pO2 with no change in pH. During mixed infections a significant decline in the IP pO2 and pH at 6 hours in those groups infected with both SFA and EC of a moderate, normally sublethal inoculation was observed, while arterial pO2 was unchanged and arterial pH was decreased only slightly. Concomitantly there was a significant increased number of aerobic bacteria in those groups with SFA as adjuvant compared to similar inocula without SFA. This study demonstrates the complex interactions of bacteria, sterile particulate adjuvant (SFA), and the host peritoneum. It suggests that the combination of SFA and aerobic bacteria alter the peritoneal environment to one permitting anaerobic growth and promoting abscess formation.

Transient and distant infections alter later intraperitoneal abscess formation.

Transient nosocomial infections, such as line sepsis and pneumonia, are common in today's critical care patient population. Although generally well treated, the effect of these transient antigen exposures on the immune system is unclear. We have previously shown that prior intraperitoneal inoculation with live bacteria leads to increased numbers of intraperitoneal abscesses. Data presented here demonstrate in a murine model that two immunizations with live Escherichia coli, Bacteroides fragilis, or both, administered systemically via intracardiac injection or at a focal distant site in subcutaneous tissue, significantly increased the number of mixed E coli/B fragilis intraperitoneal abscesses when induced 1 week later. Further, immunization with E coli, either alone or in combination with B fragilis, increased the total number of anaerobes recovered per mouse. Transient or focal sublethal infections can significantly alter an animal's immune response to later infectious insults, particularly the formation of intraperitoneal abscesses.

Modern concept for a new, improved microporous skin-closure tape.

A new improved skin-closure tape, Proxi-Strip, has been developed. It has unique performance and handling characteristics that are ideally suited for wound closure. Most importantly, its adhesive provides a strong level of shear adherence to the skin. Its backing is extensive under low forces to accommodate swelling of the underlying tissue. Its great air porosity and water transmission rates augur well for the presence of dry skin under the tape. An antistatic compound has been added to the tape that maintains its flat configuration and facilitates its application to skin. On the basis of these unique performance and handling characteristics, Proxi-Strip skin-closure tape is recommended for wound closure.

Performance of new wound closure tapes.

The purpose of this study was to determine the performance of six different wound closure tapes using a battery of standardized tests that included breaking strength, elongation, air porosity, and shear adhesion. The results of these tests were incorporated into a ranking system that provided an index of the overall performance of each tape. Because Nichi-Strip, Curi-Strip and Steri-Strip wound closure tapes achieved the highest rankings, we recommend their use in the emergency department.

Emergency department management of mammalian bites.

Mammalian bites have reached epidemic proportions with more than one half million people being bitten by an animal or another person. Although the bite wound may initially appear to be innocuous, it may lead to severe complication that can be prevented by a timely and comprehensive treatment program that is outlined in this report. Our approach to these challenging injuries includes a complete evaluation of the injury, planned surgical intervention, antimicrobial therapy, immunoprophylaxis, and appropriate postoperative care.

Practical technique for quantitating anaerobic bacteria in tissue specimens.

Quantitative bacteriology has considerable influence on the care and management of surgical wounds. Heretofore, these techniques have been limited to measurements of aerobic bacteria. A technique is reported herein which permits quantitation of obligately anaerobic bacteria in tissue specimens. This technique is easily reproduced in any clinical laboratory and eliminates the need for expensive anaerobic chambers.