Cost analysis of antibiotics in the management of perforated or gangrenous appendicitis.

Costs associated with treating patients for gangrenous or perforated appendicitis were compared. Patients received single agent therapy with cefoperazone or cefamandole or combination antibiotics consisting of clindamycin and serum level-adjusted gentamicin. Forty-eight patients received cefamandole, 47 received cefoperazone, and 52 received combination clindamycin and gentamicin. Costs to the pharmacy for drugs were greater for the combination therapy; however, the higher failure rate associated with the cephalosporins created greater expenses for the single agent therapy than for combination therapy.

Improved methods for estimating initial heparin infusion rates.

Two methods of calculating heparin infusion rates for patients with venous thrombotic disease were compared; one method was based on a one-compartment pharmacokinetic model, the other on patient weight. Sixty-eight patients with presumed thromboembolic disease were started on continuous i.v. heparin sodium (porcine) using an infusion pump. Patients were divided into two groups--the infusion rate of Group I was based on patient weight (77 units/kg/4 hrs) and the infusion rate of Group 2 was determined by a pharmacokinetic equation based on a one-compartment heparin model. Heparin effect was measured by an activated partial thromboplastin time (APTT). The initial heparin infusion rate for Group 1 (4,784 +/- 672 units/4 hrs) was significantly greater (p less than 0.039, two-sample t-test) than that for Group 2 (4,413 +/- 779 units/4 hrs), but the variances of the rates were not significantly different (p = 0.40, ratio of variance F-test). Both methods for estimating initial heparin infusion rates gave mean APTT values in the center of the therapeutic range, but the variance in the APTTs of Group 2 patients was significantly smaller (p = 0.004) than that of Group 1. The pharmacokinetic model was more precise and reliable. This model should be valuable for insuring heparin's therapeutic effect without exposing patients to the potential risk of hemorrhage.

Controlled comparison of cefmetazole with cefoxitin for prophylaxis in elective cholecystectomy.

Prophylactic antibiotics are given routinely to patients undergoing surgical treatment of the biliary tract to prevent postoperative infection if risk factors for postoperative sepsis are present. Cefmetazole (CM) is a new broad spectrum parenteral cephamycin antibiotic. This drug possesses a spectrum of activity against a wide range of gram-negative and gram-positive bacteria that is similar to cefoxitin (CX), an antibiotic widely used for prophylaxis with operations upon the abdomen. In this study, there was a random selection of two patients to receive CM to every one patient to receive CX. The dose of CM was 1 gram given intravenously every eight hours for three doses beginning 30 minutes before the operation; three doses of CX were given intravenously, 2 grams every six hours. Fifty-two evaluable patients comprised the CM group and 26, the CX group. The risk factors for postoperative infection were acute cholecystitis (CM, seven patients; CX, one patient), evidence from imaging procedure suggesting need for exploration of the common duct (CM, six; CX, one), hyperbilirubinemia (CM, eight; CX, four), hyperamylasemia (CM, 17; CX, seven); age of 60 years or more (CM, six; CX, one), obesity (CM, 36; CX, 14) and diabetes mellitus (CM, four; CX, five). Operative bactibilia and the organisms were comparable in both groups. Postoperative days of fever greater than or equal to 38 degrees C. (oral) (CM, 0.83 +/- 1.20; CX, 0.58 +/- 0.96) and hospitalization (CM, 6.59 +/- 2.20; CX, 5.04 +/- 1.26) were similar. Postoperative septic complications at the operative site occurred in two patients in the CM group (4 per cent) and in none of the patients in the CX group (p = 0.4; N.S., Fischer exact test). These two antibiotics had similar efficiency in preventing postoperative infections.

Intramuscular imipenem as adjuvant therapy for acute cholecystitis and perforated or gangrenous appendicitis.

An open-label prospective study was performed employing intramuscularly administered imipenem as an adjunct to surgery in 20 patients with acute cholecystitis and 24 patients with perforated or gangrenous appendicitis. Three (12.5%) septic failures occurred in appendicitis patients and 2 (10%) failures in cholecystitis patients. There were no deaths. Adverse effects were minor, and there was no toxicity. Although failures were not associated with in vitro resistance, Pseudomonas spp. were recovered from 2 of 3 appendicitis failures. Intramuscular imipenem appeared to be an effective single-drug antimicrobial when used as an adjunct to surgery in patients with acute cholecystitis or perforated appendicitis. It should be a more cost-effective alternative to the current multiple-drug therapy frequently employed in patients with intra-abdominal sepsis.

Influence of manufacturer lot number on pharmacokinetic manipulation of gentamicin serum concentrations.

A prospective, randomized trial was performed to study the impact of lot variation on pharmacokinetic manipulation of serum gentamicin concentrations. Twenty patients receiving gentamicin were randomized prospectively into two groups. Group I patients had blood samples obtained before and after two doses during their hospital regimen using gentamicin from the same lot number. Group II patients had the samples obtained around two doses using different lot numbers of gentamicin. Pharmacokinetic parameters were calculated assuming a one-compartment model and were compared between the initial and subsequent set of serum concentrations. For Group I, the gentamicin distribution volume (Vd) did not differ (mean change, -0.007 L/kg, or mean absolute percentage change, 20.8%). Group II also did not have a significant mean change in Vd (0.023 L/kg, or mean absolute percentage change, 18.7%). The gentamicin Vd did not appear to change over time whether gentamicin was administered using identical or differing lot numbers.

Surgically treated gangrenous or perforated appendicitis. A comparison of aztreonam and clindamycin versus gentamicin and clindamycin.

A randomized, double-blinded, controlled clinical study of 84 patients with surgically treated gangrenous or perforated appendicitis was done to compare the efficacy of the combination of aztreonam, the first monobactam antibiotic, with gentamicin when either was combined with clindamycin. Fifty-six patients who were treated with aztreonam and clindamycin (A/C) and 28 patients who were treated with gentamicin and clindamycin (G/C) fulfilled criteria for evaluation. A matched historic control group of 56 G/C patients was also included for comparison. All measures of outcome, including days of fever, hospitalization, antibiotic therapy, and the incidence of antibiotic failures, were similar. It was concluded that aztreonam was as effective as gentamicin in this study and may offer some advantages with regard to toxicity and serum drug level monitoring.

Evaluation of two different dosage regimens of clindamycin and the penetration into human appendix.

The study objective was to evaluate serum, peritoneal fluid, and appendix tissue concentrations of clindamycin using two differing clindamycin regimens. Patients age 16 years and older who were about to undergo appendectomies were randomly assigned to receive gentamicin 1.5 mg/kg every 8 h admixed with clindamycin 900 mg every 8 h (8-h group) or clindamycin 600 mg every 6 h given separately (6-h group). Doses of each regimen were given preoperatively. Serum, peritoneal fluid, and appendix tissue samples were obtained intraoperatively, and frozen at -70 degrees C for gas chromatographic drug analysis. Twenty-one patients were evaluated, 11 patients in the 8-h group and 10 patients in the 6-h group. Values are reported as means +/- standard deviations. The values in the 8-h group were 12.3 +/- 14.1 micrograms/ml, 8.7 +/- 3.9 micrograms/ml, and 9.8 +/- 10.3 micrograms/g for serum, peritoneal fluid, and appendix tissue, respectively. The values in the 6-h group were 9.7 +/- 5.1 micrograms/ml, 5.8 +/- 5.3 micrograms/ml, and 6.2 +/- 4.9 micrograms/g for serum, peritoneal fluid, and appendix tissue, respectively. The 6-h group received more doses preoperatively (1.8 +/- 0.6) than the 8-h group (1.2 +/- 0.4; p less than 0.05). No differences in penetration of clindamycin into the serum, peritoneal fluid, and appendix tissue for the 8-h group and the 6-h group were noted. The study revealed a similarity in penetration of clindamycin into the serum, peritoneal fluid, and appendix tissue using either clindamycin 900 mg given by intermittent intravenous infusion every 8 h admixed with gentamicin or clindamycin 600 mg given every 6-h separately.

The role of Pseudomonas species in patients treated with ampicillin and Sulbactam for gangrenous and perforated appendicitis.

A prospective, randomized, double-blinded comparison of Sulbactam and ampicillin and clindamycin and gentamicin is described. The combination of ampicillin and Sulbactam was not as effective in the management of perforated appendicitis and gangrenous appendicitis as was clindamycin and gentamicin. While both combinations of antibiotics had good anaerobic activity and failures were not associated with the recovery of Bacteroides fragilis group organisms, infectious complications were seen in patients from whom Pseudomonas were isolated. These pseudomonads were not nosocomially acquired and were found especially in patients with perforated appendicitis. We concluded that the combination of clindamycin and gentamicin, although less convenient to administer to the patient, remains the adjunctive antibiotic management of choice for perforated or gangrenous appendicitis. The epidemiologic factors of Pseudomonas species as a primary pathogen in peritonitis deserves further attention.

Pharmacokinetics of parenteral sulbactam in patients with appendicitis.

The distribution and elimination of a new beta-lactamase inhibitor, sulbactam, were characterized in patients with gangrenous or perforated appendicitis. Using a two-compartment model, the distribution volumes for the central and total body were approximately 11 and 25 L, respectively. Sulbactam is rapidly distributed and eliminated with rate constants of about 3.7 and 0.7 h-1, respectively. Mean total body clearance was 311 ml/min. In contrast to previously reported data from normal subjects, surgical patients have more rapid total body clearance and larger steady-state distribution volumes.

Perforated and gangrenous appendicitis: an analysis of antibiotic failures.

The relationships between resistant pathogens, serum levels of gentamicin, and the outcomes of gangrenous or perforated appendicitis were analyzed in 147 patients. Failure to cure the infection occurred significantly more frequently among patients treated with cefoperazone or cefamandole than among those treated with clindamycin and gentamicin in combination. The failures were associated with recovery of resistant Bacteroides fragilis from intraoperative cultures. Pseudomonas species were also associated with failures, their in vitro susceptibility not correlating with clinical cure. Patients with gentamicin peak serum levels of less than 6 micrograms/ml in the first three days were not more likely to be associated with failure than were patients with higher levels. These clinical observations indicate that antibiotic therapy of intra-abdominal sepsis should include antibiotics with in vitro activity against B fragilis and that precise adjustments of gentamicin levels may not improve outcome. In addition, Pseudomonas species may play a significant role in some of these infections.

Matched case-control study of adjusted versus nonadjusted gentamicin dosing in perforated and gangrenous appendicitis.

A matched case-control study of the efficacy of gentamicin dosage adjustment through the use of pharmacokinetic analysis of serum drug concentrations in patients treated by appendectomy for perforated or gangrenous appendicitis was performed. Two groups of patients were compared. In one group gentamicin was initiated preoperatively at 1.5 mg/kg Intravenous Piggy Back (IVPB) every 8 h. Postoperatively, serum levels were obtained to maintain peak concentrations within a range of 6-8 micrograms/ml. The comparison group was given gentamicin without measurement of drug levels. Both groups received clindamycin 600 mg IVPB every six h. Matched cases and control subjects were compared, controlling for pathologic state of the appendicitis, age, and sex. The patients were predominantly young men with normal renal function. More patients in the nonadjusted group had infectious complications than in the dose-adjusted group. There were seven failures (11.3%) in the nonadjusted group compared with only one failure (1.6%) in the dose-adjusted group, a significant difference (p = 0.03). Among the nonadjusted group, the complications were four abdominal abscesses, two wound infections, and one persistent high fever. There was no evidence of nephrotoxicity in either group. Our recommendations are that patients who are to undergo appendectomy for perforated/gangrenous appendicitis should be treated with clindamycin and gentamicin at a dose of 1.5 mg/kg. With normal renal function, an interval of 8 h is appropriate. Serum gentamicin levels should be obtained and the dose adjusted to maintain peak concentrations of 6-8 micrograms/ml.

Imipenem therapy for perforated and gangrenous appendicitis.

A matched patient control study of imipenem therapy of patients with perforated or gangrenous appendicitis was performed. Thirty-three patients treated with imipenem and cilastatin were compared with 66 control patients treated with clindamycin and gentamicin. Patients were matched for age and surgical pathologic factors. Twenty-five of the 33 imipenem treated patients had perforated (two with abscesses) and nine had gangrenous appendicitis. Anaerobes were recovered from 23 of 32 (72 per cent), anerobes from 31 of 32 (97 per cent) and Pseudomonas from six (26 per cent) of the 23 with perforated appendicitis. Only one isolate, a Fusobacterium species was resistant to imipenem. Enterococci were isolated only from three imipenem treated patients, all were susceptible and were not associated with failures. Frequency of other pathogens isolated was similar for the imipenem and clindamycin and gentamicin patients. One failure occurred in the imipenem treatment group. Failures and adverse reactions were not different for the two groups. The study would have detected as significant (p equals 0.03) a 9 per cent difference in failure rates. Mean days of fever of more than 38 degrees C and days of hospitalization were fewer (p less than 0.05) for imipenem treated patients even when only patients with perforated appendicitis were compared. Days to return of intestinal function were fewer for control patients. Imipenem and cliastatin appeared to be an effective antimicrobial agent used as an adjunct to surgical treatment for peritonitis associated with appendicitis even when caused by Bacteroides fragilis group organisms or Pseudomonas species, or both.

Gentamicin penetration into diseased appendix tissue.

Gentamicin concentrations in appendix tissue, serum, and peritoneal fluid were obtained in suspected cases of gangrenous or perforated appendicitis. Despite widely ranging gentamicin concentrations, no infectious complications developed. Correlations were made between the pathologic state of the tissue and the tissue gentamicin concentrations. Correlations were also made with tissue gentamicin concentrations and the time after the antibiotic dose to the time of sampling.

Comparison of physician and pharmacist management of anticoagulant therapy of inpatients.

The management of anticoagulant therapy for hospitalized patients by seven certified pharmacist prescribers and one physician was compared. Eighty-one consecutive patients referred to the anticoagulation service were randomly assigned to two groups. For patients in the pharmacist-prescriber group, the physician independently monitored laboratory results and simulated heparin and warfarin doses. The roles of pharmacist and physician were reversed for patients in the physician-prescriber group. According to an established protocol, adjustments in heparin sodium infusion rate were based on activated partial thromboplastin time (PTT); warfarin sodium dosage was adjusted using a proconvertin and prothrombin (P&P) method. Heparin doses, warfarin doses, and clotting-test results were compared for patients in the two prescriber groups; simulated and actual doses also were compared. Patients were observed for complications of anticoagulant therapy. There were no significant differences in the mean heparin and warfarin doses administered to patients in the two prescribed groups. Similarly, PTT and number of days to reach therapeutic P&P were not significantly different. Within each group, the mean prescribed and simulated heparin doses were not significantly different. There were no episodes of major bleeding, but four patients in the pharmacist-prescriber group had minor bleeding. While the results are not applicable to all pharmacists or all settings, the certified pharmacist prescribers in this study adjusted anticoagulant therapy as well as an experienced physician.