The role of glucocorticoids in the regulation of thyroid function in man.

The diurnal variation in thyroidal iodine release previously observed in euthyroid subjects appears to correlate with variations in serum immunoassayable thyrotropin (TSH). The hypothesis is advanced that this diurnal rhythm seems to be primarily regulated by a negative feedback action of circulating hydrocortisone. The administration of maintenance doses of hydrocortisone to patients with primary adrenal insufficiency and pharmacological doses to euthyroid subjects was accompanied by an acute suppression in both thyroidal iodine release and serum TSH values. An escape from glucocorticoid suppression was observed to occur in 2 or 3 days with the resumption of a near-normal thyroidal iodine release rate but was accompanied by a dampening or absence of the normal diurnal rhythm. Withdrawal of pharmacological doses of glucocorticoids in euthyroid subjects and maintenance doses in primary hypoadrenal patients was accompanied by transient stimulation of both serum TSH and thyroidal iodine release values. The study of a patient before and after cryohypophysectomy indicated that the rebound response in thyroid release after steroid withdrawal may be a useful testing procedure to indirectly assess the hypothalamicpituitary reserve capacity of TSH.

Potential of topical norfloxacin therapy. Comparative in vitro activity against clinical ocular bacterial isolates.

Norfloxacin, a new fluoroquinolone antibiotic related to nalidixic acid, was evaluated as a topical agent for clinical efficacy in bacterial eye infections. This study reports on the comparative in vitro activity of norfloxacin and ten topical antibiotics (nalidixic acid, polymyxin B, colistin, bacitracin, chloramphenicol, sulfamethoxazole, tetracycline, erythromycin, gentamicin, and tobramycin) against 203 pathogenic eye isolates of 17 genera (37 species). In general, norfloxacin had the greatest potency and broadest spectrum of activity of the agents tested. It was active against Staphylococcus aureus (minimal inhibitory concentration against 90% [MIC90], less than or equal to 1.0 microgram/mL), coagulase-negative staphylococci (MIC90, less than or equal to 1.0 microgram/mL), Pseudomonas aeruginosa (MIC90, less than or equal to 1.0 microgram/mL), and Haemophilus organisms (MIC90, less than or equal to 1.0 microgram/mL).

Prevalence of gastric metaplasia, inflammation, and Campylobacter pylori in the duodenum of members of a normal population.

Mucosal biopsies were obtained from 116 asymptomatic volunteers (50% were male; mean age, 46 years; age range, 19-91 years) to study the prevalence of duodenal gastric metaplasia (GM) and its association with inflammation and Campylobacter pylori in a normal population. GM was identified in 25 subjects (22%). Eighty-three subjects (72%) had histologic duodenitis, but in only 10 did the infiltrate include neutrophils (grade 2 duodenitis). C. pylori was found in the stomach in 36 subjects (31%), all of whom had gastritis, but was not identified histologically in the duodenum. There were no significant differences between the overall frequency of duodenitis and either GM or antral C. pylori. Although the frequency of severe (grade 2) duodenitis was not significantly different between those with and those without GM, grade 2 duodenitis was found in 9 of 36 subjects with antral C. pylori but in only 1 of 80 without antral C. pylori (P less than 0.001). These findings suggest that gastric metaplasia is a common finding in the normal population and that grade 1 duodenitis is most likely clinically unimportant, whereas grade 2 duodenitis is usually associated with antral C. pylori.

Susceptibility testing of Listeria monocytogenes. A reassessment of bactericidal activity as a predictor for clinical outcome.

In vitro susceptibility testing of Listeria monocytogenes most often reveals both ampicillin and penicillin as inhibitory as opposed to bactericidal with activity comparable to chloramphenicol and tetracycline. Yet, the former two penicillins are more effective for Listeria meningitis than are the latter agents. Accordingly, we reassessed the bactericidal activity of agents used in listeriosis in order to determine in vitro methodology that would be more predictive of clinical outcome. We found that bactericidal activity for greater than 48 hr by either minimum inhibitory-minimum bactericidal concentration (MIC-MBC) testing or time-kill kinetic studies was the best predictor of clinical efficacy. This correlation may be due to Listeria being a slow-growing microorganism. In addition to ampicillin and penicillin, we found trimethoprim-sulfamethoxazole, vancomycin, and imipenem to exhibit bactericidal activity for 48 hr. For the first two agents, this is in agreement with the results of clinical experience.

Comparative in vitro activities of norfloxacin (MK-0366) and six commonly used antimicrobial agents against 199 urinary isolates showing various degrees of antibiotic resistance.

The in vitro activity of norfloxacin (MK-0366), a new oral antimicrobial agent, was compared to that of ampicillin, tetracycline, cefazolin, nitrofurantoin, nalidixic acid, and trimethoprim against 199 gram-negative urinary isolates. Among these isolates were ampicillin-resistant Escherichia coli and gentamicin-resistant Pseudomonas aeruginosa and Serratia marcescens. Norfloxacin was the most active antimicrobial agent tested against all isolates studied; it was the only agent active against P. aeruginosa and S. marcescens.

Pharmacoeconomics of piperacillin/tazobactam and imipenem/cilastatin in the treatment of patients with intra-abdominal infections.

Costs involved in using piperacillin 4 g/tazobactam 500 mg, given as intermittent intravenous infusions every 8 hours, were compared with those for imipenem/cilastatin 500 mg, given as intermittent intravenous infusions every 6 hours, for the treatment of patients with gangrenous or perforated appendicitis. A total of 88 patients were included in our cost analyses: 42 patients in the piperacillin/tazobactam group and 46 patients in the imipenem/cilastatin group. Durations (mean +/- SD) of antibiotic therapies were 7.8 +/- 3.3 days and 7.1 +/- 2.6 days for the piperacillin/tazobactam and imipenem/cilastatin groups, respectively. No statistical significance was found for the difference in duration of therapy (P = 0.376). Total drug treatment costs were $538.83 +/- $385.33 for the piperacillin/tazobactam group and $687.66 +/- $345.37 for the imipenem/cilastatin group. This difference in treatment cost was statistically significant (P = 0.0001). The need for laboratory tests and the use of other medications were not different between the two groups. Total hospital-days charges were higher for the piperacillin/tazobactam group ($18,339.76 +/- $6090.38) compared with the imipenem/cilastatin group ($16,150.00 +/- $5088.60) (P = 0.052). These findings suggest that length of hospital stay should be the economic focus of antibiotic therapy.

Meropenem versus tobramycin with clindamycin in the antibiotic management of patients with advanced appendicitis.

BACKGROUND: Meropenem (MP), a new carbapenem antibiotic, has excellent antimicrobial activity against the enteric flora commonly encountered in acute appendicitis. Although similar to imipenem, it may have clinical advantages. STUDY DESIGN: We compared patients with advanced appendicitis (gangrenous or perforated) treated with 1,000 mg MP every eight hours with those given the combination of tobramycin 5 mg/kg/day at eight hour intervals and clindamycin 900 mg every eight hours. Both treatments were given intravenously. Patients were randomized to either group of the double-blind study. RESULTS: Of 129 evaluable cases, 63 received MP and 66 received both tobramycin and clindamycin (T/C). The two groups were similar in age, sex, and severity of disease. The mean number of days of postoperative fever (MP = 3.1 +/- 1.7 SD compared to T/C = 4.4 +/- 2.2 SD, p < or = 0.01), days of antibiotic therapy (MP = 6.1 +/- 1.6 SD compared to T/C = 7.3 +/- 2.2 SD, p = 0.01), and therefore hospital stay (MP = 8.0 +/- 3.5 SD compared to T/C = 9.4 +/- 2.6 SD, p < 0.01) were significantly better for patients treated with MP. No difference was found between the numbers of failures in each group (MP = 5 compared to T/C = 6). CONCLUSIONS: This study demonstrates a small but significant reduction (approximately one day) in post-operative fever, duration of antibiotic treatment, and hospital stay for patients treated with MP compared to those treated with T/C.

Analysis of cefepime tissue penetration into human appendix.

Cefepime is a new extended-spectrum cephalosporin with gram-positive and gram-negative coverage including Staphylococcus aureus and Pseudomonas aeruginosa. We evaluated the drug's plasma, peritoneal fluid, and appendix tissue concentrations in patients with a postoperative diagnosis of perforated or gangrenous appendicitis. Patients 18 years of age or older were randomly assigned to receive either cefepime 2 g every 12 hours plus metronidazole 500 mg every 6 hours intravenously, or gentamicin 1.5 mg/kg plus clindamycin 900 mg every 8 hours intravenously. During surgery, appendix tissue, plasma, and peritoneal fluid samples were obtained, and frozen at -70 degrees C for high-pressure liquid chromatographic analysis. Thirty-five patients with perforated (26) or gangrenous (9) appendicitis had concentrations acceptable for analysis. The mean time between the administration of cefepime and the time of sampling (referred to as delta time) was 5.99 +/- 3.75 hours (mean +/- SD). The values for plasma (n = 34), tissue (n = 33), and peritoneal fluid (n = 25) concentrations were 16.27 +/- 21.87 micrograms/ml, 4.84 +/- 6.15 micrograms/g, and 14.4 +/- 22.84 micrograms/ml, respectively. The appendix tissue:plasma ratio was 0.66 +/- 0.52 and the peritoneal fluid:plasma ratio was 0.66 +/- 0.51. Spearman rank correlations indicated statistically significant correlations between plasma concentration (r = -0.889; p less than 0.0001), peritoneal fluid concentration (r = -0.783; p = 0.0002), and appendix tissue concentration (r = -0.704; p = 0.0016) versus delta time.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibiotic management of surgically treated gangrenous or perforated appendicitis. Comparison of gentamicin and clindamycin versus cefamandole versus cefoperazone.

A study of 130 adult patients with surgically treated gangrenous or perforated appendicitis was undertaken to evaluate the efficacy of three antibiotic regimens. Forty-eight patients received cefamandole, 40 were given the combination of clindamycin and gentamicin, and 42 were treated with cefoperazone. Side effects from these antibiotics were infrequent and mild. When all cases were compared for infectious failure, clindamycin-gentamicin showed a clear advantage over cefamandole. Because of the heterogeneity of the total study population, patients with perforation and peritonitis were compared separately. This analysis confirmed the advantage of clindamycin-gentamicin over cefamandole. In addition, it appears that clindamycin-gentamicin is more efficacious than cefoperazone.

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.

In vitro contamination of "piggyback/heparin lock" assemblies: prevention of contamination with a closed, positive locking device (Click-Lock).

Direct contact and airborne transmission are established modes of microbial contamination of standard intravenous (iv) assemblies such as piggyback and heparin lock. In this study, 60% of the standard iv assemblies inoculated with Staphylococcus aureus (S. aureus) at the barrel of their exposed needle grew these organisms when cultured in a Soy Casein Digest Broth (SCDB). Also, 40 closed, positive locking iv assemblies (Click-Lock) were inoculated at possible contamination sites, and none of these assemblies grew S. aureus in a SCDB. These in vitro studies suggest that a closed, positive locking iv assembly such as the Click-Lock device may substantially reduce, and potentially prevent contamination of iv systems.

Value of antibiotic prophylaxis in periodontal surgery.

THE MORBIDITY and incidence of bacteremia in periodontal surgery with or without cephalexin prophylaxis were assessed in adults on the basis of clinical evaluations and blood cultures. Cephalexin reduced the incidence of polymicrobic bacteremias. There was no correlation between objective signs of tissue healing and antibiotic coverage in treated or nontreated patients. In vitro antibiotic susceptibility data showed that cephalexin was active against the aerobic and anaerobic bacteria isolated from blood specimens taken during surgery.

Ceftazidime/clindamycin versus tobramycin/clindamycin in the treatment of intra-abdominal infections.

In order to assess the efficacy and toxicity of ceftazidime as a substitute for aminoglycosides in the treatment of intra-abdominal sepsis, a prospective randomized trial was conducted. Ninety-four patients (49% trauma) were randomized to receive ceftazidime/clindamycin (CAZ/C) (n = 47) or tobramycin/clindamycin (T/C) (n = 47). CAZ (2.0 gm) and C (0.9 gm) were administered intravenously every 8 hours while T dosage was adjusted to maintain peak (5-8 mg/L) and trough (less than 2 mg/L) concentrations. Age, sex, baseline serum creatinine, and etiology of infection were comparable in the two groups. Clinical cure was similar in culture-positive and culture-negative patients who received CAZ/C (94% vs 88%). The clinical cure rate however was significantly lower in the T/C culture positive (73%) than in the culture negative patients (100%) (P = 0.016). Pathogenic organisms were eradicated in 100% (30/30) and 76% (13/17) of CAZ/C and T/C patients, respectively (P = 0.0006). Nephrotoxicity Nephrotoxicity or ototoxicity was observed in none of the CAZ/C patients and in one and two T/C patients, respectively. CAZ/C more effectively eradicated the bacteria isolated from these patients and no significant difference in clinical response was observed in culture-positive patients. These findings plus the lack of toxicity suggest that CAZ/C is an effective alternative for treatment of IAI.

Prospective randomized study of two different doses of clindamycin admixed with gentamicin in the management of perforated appendicitis.

Septic complications after surgery for enterogenous peritonitis are minimized by adjuvant antibiotics effective against aerobes and anaerobes. Historically, "gold standard" therapy included an aminoglycoside plus clindamycin, the latter given at 600 mg intravenous piggyback (IVPB), every 6 hours. Clindamycin pharmacokinetics suggests that it can be given q8h and admixed with gentamicin, thereby markedly reducing the cost of administration. Although this is now common practice, there is no prospective study comparing the efficacy of the two dose schedules in peritonitis. This study was designed to test the hypothesis regarding the clinical efficacy of the two regimens. One hundred twenty-six patients with gangrenous (n = 34) or perforated appendicitis (n = 91) were randomized (2:1) to receive gentamicin admixed with clindamycin 900 mg IVPB every 8 hours (Group I n = 80) or gentamicin IVPB q8h plus clindamycin 600 mg IVPB every 6 hours (Group II n = 46). Appendectomy was performed, and aerobic and anaerobic cultures were obtained. Twenty-one patients had simultaneous determinations of clindamycin levels in plasma, peritoneal fluid, and appendix. Outcome analysis revealed no significant differences in postoperative days of fever, days non per os, antibiotic therapy, or hospitalization. There were 6 failures (4 abscesses and 2 wound infections) in Group I and 4 failures (1 abscess and 3 wound infections) in Group II. Both antibiotic regimens provided clinically equivalent results in mixed infections due to aerobic and anaerobic bacteria. The admixed clindamycin, administered every 8 hours, results in at least 20% reduction in costs. This is an important consideration.

Coccidioides immitis presenting as a hyphal form in cerebrospinal fluid.

This article reports a case of Coccidioides immitis that presented as a hyphal form in a 38-year-old patient. The organism was observed growing exclusively as hyphae in the cerebrospinal fluid by microscopic examination. Coccidioides immitis was the only organism cultured. The identification of C immitis was confirmed by both standard culture methods and DNA probe studies.

Amniotic fluid contamination during internal fetal monitoring.

The risk of infections associated with intrauterine fetal monitoring was evaluated in 30 consecutive labors. Amniotic fluid samples collected through the intrauterine catheter were found to be contaminated with bacteria in 15 of 30 consecutively monitored patients during labor. Aerobes were the exclusive isolates in eight, anaerobes in five and both in two patients. Eleven patients developed puerperal fever. One patient developed gonococcal amnionitis, and her newborn infant later developed gonococcal septicemia. The equipment--catheters and fetal scalp electrodes--was sterile. The overall risk of infection associated with internal monitoring in our study was 50% for amniotic fluid contamination and 37% for puerperal febrile morbidity.

A cost comparison of intramuscular versus intravenous imipenem.

Previously reported clinical trials of imipenem-cilastatin 500 mg given intravenously every 6 hours (intravenous group) and imipenem-cilastatin 750 mg given intramuscularly every 12 hours (intramuscular group) were analyzed for relative cost savings. Acquisition costs were significantly higher for the intravenous group for intravenous supplies (30.6 +/- 7.9 dollars) when compared to the intramuscular group (0.98 +/- 0.03 dollars) (p less than 0.05). Also, significantly higher cost (p less than 0.05) was noted for salaries of pharmacists and technicians for manufacturing in the intravenous group (5.8 +/- 1.5 dollars) as compared to the intramuscular group (2.4 +/- 0.7 dollars). Nursing administration costs were greater for the intramuscular group (15.6 +/- 4.8 dollars) when compared to the intravenous group (11.7 +/- 3.0 dollars). Incorporating all appropriate costs, the mean total drug therapy costs (TRX$) were significantly greater (p less than 0.01) for the intravenous group (458.17 +/- 175.17 dollars) as compared to the intramuscular group (298.0 +/- 114.76 dollars). Thus, the dosing of imipenem-cilastatin 750 mg intramuscularly every 12 hours is a more cost effective method of drug delivery with equal efficacy and safety when compared to imipenem-cilastatin 500 mg given intravenously every 6 hours.

Transmission of parasitic and bacterial infections through blood transfusion within the U.S.

The American public has become aware that viral infections can be transmitted by blood transfusions; however, less attention has been paid to nonviral agents that are similarly transmitted. Although donors are tested routinely for serologic evidence of Treponema pallidum infection (syphilis), there are no other bacterial infections for which donors are routinely tested, and no testing is done routinely to detect parasitic infections. Although current preventive strategies appear effective in preventing the transmission of nonviral agents by transfusion, changing population demographics, increased travel and immigration, and increased occurrence of certain asymptomatic bacterial infections in blood donors may require new policies to maintain the safety of the U.S. blood supply. This review focuses on the parasitic and bacterial infections that might pose a risk to transfusion recipients in the U.S.

Comparative in vitro activities of trovafloxacin (CP-99,219) against 221 aerobic and 217 anaerobic bacteria isolated from patients with intra-abdominal infections.

Four hundred thirty-eight bacteria cultured from specimens of patients with serious intra-abdominal infections were tested by agar dilution against trovafloxacin and other quinolones and antimicrobial agents. Trovafloxacin inhibited 435 strains (99.3%) at < or =2 microg/ml. All the quinolones had similar activities against Enterobacteriaceae and Pseudomonas sp., but trovafloxacin showed superior activities against streptococci, enterococci, and anaerobic organisms. Because of its excellent in vitro activities against diverse bacteria, trovafloxacin has potential use as a single agent for polymicrobial infections.