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Biomedical subjects

A B Kaiser

Publications and source records attributed to A B Kaiser.

At least 19 recordsLinked to original sources
PubMed1994

Comparative prophylactic efficacies of ciprofloxacin, ofloxacin, cefazolin, and vancomycin in experimental model of staphylococcal wound infection.

Recent shifts in the species and antibiotic resistance patterns of bacteria causing nosocomial infections present new challenges for providing effective prophylaxis in surgery. Traditional regimens lack activity against methicillin-resistant staphylococci and many gram-negative species causing nosocomial infections. The new fluoroquinolones exhibit in vitro activity against many emerging surgical wound pathogens. To determine the potential of this class of antimicrobial agents for use in surgery, we compared the prophylactic efficacies of ciprofloxacin and ofloxacin with those of cefazolin and vancomycin in a guinea pig model of abscess formation. Four Staphylococcus aureus strains, one Staphylococcus epidermidis strain, and one Staphylococcus haemolyticus strain were evaluated. Vancomycin was the most effective prophylactic agent, exhibiting in vivo activity against all strains which was superior or equivalent to those of all other agents tested. Cefazolin was the least effective agent and surpassed the two quinolones in prophylactic efficacy against only one organism, a quinolone- and methicillin-resistant strain of S. aureus. The two quinolones provided excellent protection against infection with all but the quinolone-resistant isolate. The in vivo emergence of quinolone resistance among quinolone-susceptible isolates was not detected. The methicillin-resistant, quinolone-susceptible S. epidermidis and S. haemolyticus isolates were extremely susceptible to prophylaxis, exhibiting 50% infective doses above 4 x 10(6) CFU for seven of the eight antibiotic-strain combinations. We conclude that ciprofloxacin and ofloxacin may be effective antistaphylococcal agents in surgery. The role of these agents remains to be defined, and the definition should include consideration of an adverse effect upon antibiotic resistance patterns of organisms causing nosocomial infections.

Animals↗
PubMed1993

Cefamandole versus cefazolin in vascular surgical wound infection prophylaxis: cost-effectiveness and risk factors.

PURPOSE: Recent studies of perioperative antimicrobial prophylaxis have indicated an improved efficacy of beta-lactamase-stable cephalosporins compared with cefazolin, the most commonly used prophylactic agent. Previous studies in our institution have revealed a superiority of cefamandole to cefazolin in patients undergoing heart surgery, although there was no difference between cefazolin and cefuroxime in patients undergoing peripheral vascular surgery. This study was therefore designed to compare cefamandole with cefazolin in wound infection prophylaxis in clean vascular surgery. METHODS: The study was conducted from August 1990 through May 1992 and consisted of 893 patients with aortic or infrainguinal arterial procedures randomized to receive either cefamandole or cefazolin. RESULTS: The difference in infection rates associated with cefamandole versus cefazolin prophylaxis (3.2% vs 1.9%, respectively) was not significant (p = 0.42). A cost savings of approximately $95,000 per year at our institution favors the continued use of cefazolin over cefamandole. Risk factor analysis was carried out for preoperative and postoperative events that might have predisposed to infection. Only preoperative use of aspirin and the postoperative finding of a lymphocele correlated with a higher infection rate. CONCLUSIONS: Cefazolin continues to be the most cost-effective antibiotic for prophylaxis in clean vascular surgical procedures.

Adult↗
PubMed1993

Comparative prophylactic efficacy of cefazolin and vancomycin in a guinea pig model of Staphylococcus aureus wound infection.

The increasing prevalence of methicillin-resistant Staphylococcus aureus as a wound pathogen in some institutions has prompted the use of vancomycin for surgical prophylaxis, although clinical data comparing vancomycin and cephalosporins are not available. A guinea pig model was used to compare the efficacy of vancomycin and cefazolin in preventing intermuscular abscess formation by 7 S. aureus strains. Both antibiotics were administered to achieve peak serum levels at the time of bacterial inoculation, and each remained > 1 micrograms/mL for a comparable duration. Vancomycin provided equivalent protection from infection by 1 methicillin-susceptible strain and significantly better protection against 4 methicillin-susceptible and both methicillin-resistant S. aureus strains. For most strains, the bacterial inoculum with a 50% probability of causing an abscess was 2 to 4 log10-fold higher with vancomycin than cefazolin prophylaxis. Prophylaxis with vancomycin is superior to cefazolin in preventing intermuscular infection by methicillin-susceptible and -resistant S. aureus.

Animals↗
PubMed1993

Efficacy of prophylaxis with beta-lactams and beta-lactam-beta-lactamase inhibitor combinations against wound infection by methicillin-resistant and borderline-susceptible Staphylococcus aureus in a guinea pig model.

Although some beta-lactams and beta-lactam-beta-lactamase inhibitor combinations exhibit activity against methicillin-resistant Staphylococcus aureus, there remains the concern that therapeutic failures may result from the selection of resistant subpopulations. The prophylactic use of these antibiotics in clean surgery, however, may prove adequate since wound infections arise from the inoculation of small numbers of bacteria. In this clinical setting, heterogeneity in the phenotypic expression of beta-lactam resistance may facilitate antibiotic efficacy. Similarly, beta-lactamase-mediated resistance in S. aureus is dependent on inoculum size, and it may be possible to prevent infection from small inocula with relatively labile beta-lactams. To test this hypothesis, antibiotics were administered to guinea pigs as prophylaxis against infection by two methicillin-resistant strains and one borderline-susceptible strain. Following prophylaxis with sulbactam or placebo, inoculation of only a dozen or fewer bacteria had a 50% probability of creating an abscess (50% infective dose [ID50]). The efficacy of ampicillin was similar to that of cefazolin, exhibiting moderate activity against the borderline-susceptible strain (ID50s, greater than 300 bacteria) and minimal activity against the methicillin-resistant strains (ID50s, fewer than 100 bacteria). Coadministration of sulbactam with ampicillin or cefazolin yielded better results than the beta-lactam alone for five of six strain-beta-lactam combinations, including an 80-fold increase in the efficacy of ampicillin-sulbactam compared with that of ampicillin for one methicillin-resistant strain (ID50s, 2,017 and 25 bacteria, respectively). Prophylaxis with beta-lactams, especially beta-lactam-beta-lactamase inhibitor combinations, reduces the risk of wound infection by beta-lactam-resistant S. aureus.

Ampicillin↗
PubMed1992

Cefuroxime versus cefazolin as prophylaxis in vascular surgery.

Although cefazolin prophylaxis has proven efficacy in vascular surgery, Staphylococcus aureus wound infections are still an important postoperative complication. In cardiac surgery, cefazolin's susceptibility to hydrolysis by staphylococcal beta-lactamase has been proposed to account for some prophylaxis failures. To determine whether the incidence of vascular wound infections can be reduced by administering a more beta-lactamase-stable cephalosporin, we undertook a prospective, randomized trial of cefuroxime versus cefazolin. Cefuroxime was administered as a 1.5 gm dose before operation and 750 mg every 3 hours during operation. Cefazolin was given as 1 gm before operation and 500 mg every 4 hours during operation. Both agents were continued every 6 hours after operation for 24 hours. Deep wound infections developed in seven of 272 (2.6%) cefuroxime and three of 287 (1.0%) cefazolin recipients (p = 0.2). Staphylococcus aureus wound infections occurred in five cefuroxime versus two cefazolin recipients. In vitro evaluation of six of the study isolates plus an additional eight S. aureus strains from vascular wound infections showed greater susceptibility of the strains to cefazolin than cefuroxime (median minimal inhibitory concentrations of 0.5 and 2.0 micrograms/ml, respectively, p less than 0.05). Furthermore, despite its more frequent intraoperative redosing, cefuroxime exhibited lower trough serum concentrations than cefazolin. Among cefuroxime recipients, infection-associated procedures were significantly longer than infection-free procedures (p less than 0.05), suggesting that low tissue antibiotic concentrations may have contributed to the pathogenesis of these infections. In contrast, the length of the procedure was not a risk factor for infection among cefazolin recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefazolin↗
PubMed1992

Evaluation of new anti-infective drugs for surgical prophylaxis. Infectious Diseases Society of America and the Food and Drug Administration.

It has been established by substantial research that antimicrobial prophylaxis for various surgical procedures can reduce the risk of postoperative morbidity and mortality. When the incidence of infectious complications is high, the reduction with prophylaxis is most dramatic. However, even for many "clean" procedures (vascular procedures, total joint replacement), the small reduction in potentially calamitous complications justifies the use of prophylaxis. Many issues of detail remain unanswered: timing and duration of administration of antimicrobial drug; type of drug; use of topical anti-infective agents as ancillary measures; and choices for high-risk individuals and others ordinarily excluded from clinical trials. An approach to the conduct of clinical trials of anti-infective drugs for surgical prophylaxis is provided. Both general guidelines and specific recommendations for total hip replacement, colorectal operations, appendectomy, and transurethral resection of the prostate are included.

Anti-Infective Agents↗
PubMed1992

Low-inoculum model of surgical wound infection.

A model of surgical wound infection that uses low inocula of bacteria and closely simulates clinical infection involved inoculating suspensions of Staphylococcus aureus and dextran microbeads into intermuscular sites on the dorsum of guinea pigs, harvesting lesions at 72-96 h, identifying as a positive end point lesions yielding staphylococci on subculture, and using logistic regression for data analysis. Prophylaxis was placebo, ampicillin, or cefazolin, and three representative strains of S. aureus were used. A highly significant correlation (P less than .001) was observed between inoculum sizes and infection rates. Without antimicrobial prophylaxis, ID50 for each strain was less than 10 organisms; with antimicrobials, ID50 was significantly higher. Differences in the virulence of strains and in the efficacy of the antimicrobial regimens also were observed. The model should prove useful for understanding mechanisms of virulence among pathogenic bacteria and for elucidating subtle but important differences in efficacy among antibiotics used in prophylaxis.

Abscess↗
PubMed1991

Correlation of in-vitro parameters of antimicrobial activity with prophylactic efficacy in an intradermal model of Staphylococcus aureus infection.

Cephalosporins differ in their ability to prevent staphylococcal wound infection. Although the reasons for the observed differences are not fully understood, the susceptibility of cephalosporins to hydrolysis by staphylococcal beta-lactamase has been correlated with failures of prophylaxis. To investigate the effect of beta-lactamase stability and other in-vitro parameters of the bacterial-antimicrobial interaction on the efficacy of antimicrobial prophylaxis, two beta-lactamase-stable agents, cefuroxime and cefmetazole were compared to cefazolin and cefamandole in an in-vivo model of intradermal infection employing four strains of Staphylococcus aureus. Following intraperitoneal administration of a single dose of cephalosporin or placebo, guinea pigs were inoculated at multiple intradermal sites with 2 x 10(7) cfu of a strain of staphylococcus. For three strains, the area of induration at 24 h following inoculation was significantly smaller in guinea pigs receiving prophylaxis with cephalosporins versus placebo; no cephalosporin was effective against the fourth strain. Differences were also noted among the cephalosporins; prophylaxis with cefuroxime and cefmetazole resulted in smaller lesions than seen in animals given cefazolin or cefamandole. Poor correlation was noted between results of the in-vivo model and in-vitro determinants of the bacterial-antimicrobial interaction which were MIC values, time-kill curves, and the rates of beta-lactamase-mediated cephalosporin hydrolysis by the different strains. The model demonstrated unexplained failures of prophylaxis and unexpected differences in efficacy of various cephalosporins as has been described before. This study highlights the need for an improved animal model of surgical antimicrobial prophylaxis and the identification of in-vitro determinants that predict in-vivo prophylactic efficacy more accurately.

Animals↗
PubMed1990

Failure of cephalosporins to prevent Staphylococcus aureus surgical wound infections.

Approximately 35,000 Staphylococcus aureus surgical wound infections occur annually in the United States. To investigate why S aureus causes infection despite the perioperative administration of cephalosporins, we compared 35 methicillin-susceptible isolates recovered from deep wound infections that complicated cefazolin prophylaxis (18 of 1650 patients) and cefamandole prophylaxis (17 of 3702 patients) with 64 colonizing isolates from presurgical patients. Compared with both colonizing and cefamandole-associated isolates, S aureus isolates from cefazolin-associated infections were more resistant to cefazolin by specialized assays. Staphylococcus aureus isolates that produced the A and C variants of staphylococcal beta-lactamase were associated with infections following cefazolin and cefamandole prophylaxis, respectively. These isolates hydrolyze the respective cephalosporins rapidly, suggesting that staphylococcal survival after perioperative prophylaxis may be mediated by in vivo degradation of the prophylactically administered cephalosporin. These data indicate that some S aureus wound infections occur because of deficiencies in antimicrobial effectiveness that are not detectable by routine susceptibility tests. This finding has important implications for the therapy and prevention of S aureus infection.

Cefamandole↗
PubMed1990

Candidal meningitis following bacterial meningitis.

Patients with bacterial meningitis and posttraumatic and/or postsurgical access to the CSF are at risk for superinfection with Candida species. Patients who are not improving on appropriate antimicrobial chemotherapy for bacterial meningitis or are deteriorating after initial improvement should have a CSF reexamination for Candida superinfection.

Adult↗
PubMed1990

Use of extracts versus whole-cell bacterial suspensions in the identification of Staphylococcus aureus beta-lactamase variants.

We previously have shown that extracts of S. aureus isolates which produce the recognized serotypes of staphylococcal beta-lactamase (A, B, C, D) differ in the rates at which they hydrolyze selected cephalosporins, exhibiting substrate profiles which are distinctive for each serotype. In an effort to simplify the methods employed in identifying the different staphylococcal beta-lactamases, we evaluated whether distinctive substrate profiles could be obtained by using whole-cell suspensions of 115 beta-lactamase-producing isolates of S. aureus. Compared with extracts from the same strains, the whole-cell bacterial suspensions not only were simpler to prepare but enabled beta-lactamase typing of a higher proportion of the evaluated strains (86 versus 97%, respectively). Furthermore, the use of whole-cell bacterial suspensions enabled the simultaneous quantitation of the beta-lactamase activity exhibited by each strain. Additionally, by comparing the quantitative activity of beta-lactamase-induced and -uninduced preparations of the same strain, induction ratios (i.e., induced/uninduced activity) could be derived, yielding information regarding the regulation of beta-lactamase production by each strain. We believe that the utilization of whole-cell methods, such as those employed in this study, will facilitate the investigation of qualitative and quantitative differences in beta-lactamase production among clinical and reference isolates of S. aureus.

Cell-Free System↗
PubMed1990

Selecting cost-effective antimicrobial prophylaxis in surgery: are we getting what we pay for?

The acquisition, administration, and infection-related expenses associated with the use of cefazolin or cefamandole during a prospective randomized comparison of antimicrobial prophylaxis in cardiac surgery were compared. Although the acquisition cost and administration charges related to the use of cefamandole were in excess of those incurred with cefazolin, differences in the charges associated with treating the wound infections that failed prophylaxis with each regimen made cefamandole the more cost-effective prophylactic agent (mean total of $766 per cefazolin recipient vs. $315 per cefamandole recipient). Analysis of prophylactic antimicrobials should include the expenses associated with "prophylactic failures." The agent that is least expensive for the pharmacy may not be the most cost-effective choice for the institution.

Anti-Infective Agents↗
PubMed1989

Immunogenicity of the intradermal route of hepatitis B vaccination with the use of recombinant hepatitis B vaccine.

In March 1987, 32 hospital employees were enrolled in a prospective trial of intradermal recombinant hepatitis B vaccination. Enrollees were given 0.1 ml of vaccine on days 1, 30, and 180. Two weeks after the third intradermal vaccination, 81%, or 26, of the enrollees showed seropositivity (greater than or equal to 10 mIU antibody/ml) for hepatitis B surface antibody. Five of six nonresponders were given a fourth intradermal vaccination. Two additional seroconversions occurred, resulting in an overall conversion rate of 90% for recipients of up to four intradermal vaccine doses. Complications of vaccination were limited primarily to the occasional persistence (less than 6 months) of hyperpigmentation at the injection site. Administration of recombinant hepatitis B vaccine by the intradermal route proved to be a safe and effective method of vaccination. Cost savings of preexposure immunization with the intradermal versus the intramuscular route of vaccination were approximately $90 per enrollee. Efficacy and safety can be maximized by employing a fourth vaccine dose and routinely documenting seroconversion after vaccination.

Antibody Formation↗
PubMed1989

Bronchopulmonary cross-colonization and infection related to mycobacterial contamination of suction valves of bronchoscopes.

Recurrent episodes of mycobacterial cross-contamination of bronchoscopy specimens were identified in a large, tertiary-care referral center. One episode was followed by active pulmonary infection due to Mycobacterium tuberculosis. Initial epidemiologic investigation implicated the flexible fiberoptic bronchoscopes. In experiments, bronchoscopes and related equipment were exposed to a saline suspension of M. fortuitum (10(5)-10(7)/mL). Bronchoscopes were readily sterilized by routine cleaning and disinfection procedures, but the spring-operated suction valves remained contaminated, even after a 30-min exposure to 2% glutaraldehyde or after passage through a commercial bronchoscope washer. These results indicate that suction valves that have been heavily contaminated with mycobacterial organisms cannot be reliably disinfected with commercially available glutaraldehyde. Suction valves have since been routinely autoclaved after each use. No additional episodes of cross-contamination or infection have occurred over 24 mo of surveillance.

Bronchoscopy↗
PubMed1988

Overview of cephalosporin prophylaxis.

After an uncertain and highly controversial beginning, the use of antimicrobials for prophylaxis of surgical wound infection has evolved to represent state-of-the-art management of the surgical patient. Although a truly ideal prophylactic antimicrobial does not exist, the cephalosporins, particularly those of the first generation, have emerged as the mainstay of prophylaxis in surgery. However, new pathogens and newly recognized problems have necessitated a comparative evaluation of a wide variety of antibiotic regimens. The choice of an appropriate antibiotic is complicated by the lack of an adequate experimental model of infection in clean and clean-contaminated surgical procedures. Moreover, clinical trials have proved to be an inefficient method of comparing antibiotic regimens, as important variations in risk factors for infection cannot be reliably controlled. Significant differences exist among cephalosporins and between the cephalosporins and other classes of antimicrobials in several clinically important parameters: antimicrobial spectrum, serum half-life, ease of administration, tissue penetrability, cost, and incidence of allergy and toxicity. New generations of cephalosporins and new classes of antibiotics have demonstrated the potential to out-perform the first-generation cephalosporins in many of these areas. Although the first-generation cephalosporins were essential in establishing the efficacy of antibiotic prophylaxis in surgery, there are no guarantees that this class of cephalosporin, or that any cephalosporin, for that matter, will continue to dominate the prophylactic arena.

Cephalosporins↗