Maria D. Appleman

Prevalence of Helicobacter pylori Infection and Histologic Gastritis in Asymptomatic Persons

We estimated the prevalences of Helicobacter pylori (formerly called Campylobacter pylori) infection and histologic gastritis in 113 asymptomatic persons, using endoscopic biopsy of the gastric antrum and corpus. Unsuspected lesions, mainly mucosal erosions, were revealed at endoscopy in 16 subjects (14 percent). Gastritis was found in 42 subjects (37 percent), of whom 36 (32 percent of the total) were found to be infected with H. pylori on the basis of hematoxylin-eosin staining. H. pylori was not found in any of the 71 subjects with normal histologic features. Gastritis and H. pylori were noted in both the antrum and corpus in 75 percent of those infected (n = 27). The prevalence of H. pylori infection increased from 10 percent (2 of 20 subjects) in those between the ages of 18 and 29, to 47 percent (7 of 15) in those between the ages of 60 and 69, but the effect of age did not reach statistical significance. The prevalence of gastritis increased significantly with advancing age. Stepwise logistic regression analysis revealed that the relative risk for H. pylori infection associated with recent (within six months) antibiotic use was 5.8 (95 percent confidence interval, 1.5 to 22.1), whereas the relative risk was 6.5 (95 percent confidence interval, 1.4 to 29.2) for those who had never used bismuth compounds. We conclude that histologic gastritis and H. pylori infection commonly occur in the stomach of apparently normal persons and increase in prevalence with advancing age. All the subjects with H. pylori infection had gastritis, suggesting a possible etiologic role for the bacterium in the histologic lesion.

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.

In Vitro Activities of Nontraditional Antimicrobials against Multiresistant Acinetobacter baumannii Strains Isolated in an Intensive Care Unit Outbreak

ABSTRACT Fifteen multiresistant Acinetobacter baumannii isolates from patients in intensive care units and 14 nonoutbreak strains were tested to determine in vitro activities of nontraditional antimicrobials, including cefepime, meropenem, netilmicin, azithromycin, doxycycline, rifampin, sulbactam, and trovafloxacin. The latter five drugs were further tested against four of the strains for bactericidal or bacteriostatic activity by performing kill-curve studies at 0.5, 1, 2, and 4 times their MICs. In addition, novel combinations of drugs with sulbactam were examined for synergistic interactions by using a checkerboard configuration. MICs at which 90% of the isolates tested were inhibited for antimicrobials showing activity against the multiresistant A. baumannii strains were as follows (in parentheses): doxycycline (1 μg/ml), azithromycin (4 μg/ml), netilmicin (1 μg/ml), rifampin (8 μg/ml), polymyxin (0.8 U/ml), meropenem (4 μg/ml), trovafloxacin (4 μg/ml), and sulbactam (8 μg/ml). In the kill-curve studies, azithromycin and rifampin were rapidly bactericidal while sulbactam was more slowly bactericidal. Trovafloxacin and doxycycline were bacteriostatic. None of the antimicrobials tested were bactericidal against all strains tested. The synergy studies demonstrated that the combinations of sulbactam with azithromycin, rifampin, doxycycline, or trovafloxacin were generally additive or indifferent.

Pharmacokinetics of meropenem in patients with intra-abdominal infections.

Noncompartmental and compartmental analyses of meropenem disposition in patients receiving 1-g intravenous intermittent infusions every 8 h were performed. Twelve patients (one woman and 11 men) participated in the meropenem pharmacokinetic analysis. Operative findings included perforated appendicitis (five patients), gangrenous appendicitis (five patients), peri-appendical abscess (one patient), and gunshot wound to the abdomen (one patient). The most common associated adverse drug reactions to meropenem were diarrhea and increased liver enzymes. The estimated noncompartmental pharmacokinetic parameters, mean +/- standard deviation, are as follows: maximum drug concentration in plasma, 47.58 +/- 17.59 micrograms/ml; half-life, 1.04 +/- 0.19 h; elimination rate constant, 0.68 +/- 0.12 h-1; area under the concentration-time curve from 0 h to infinity, 57.5 +/- 20.12 micrograms x ml/h; total plasma clearance, 315.40 +/- 71.94 ml/min; renal clearance, 136.7 +/- 89.20 ml/min; volume of distribution at steady state, 26.68 +/- 6.88 liters; and mean residence time, 1.47 +/- 0.28 h. The two-compartment model best described meropenem disposition in our patients. Our findings differed from estimates for healthy volunteers possibly because of the physiologic changes as a result of surgery. Our findings suggest that meropenem (1,000 mg) administered intravenously every 8 h provides adequate concentrations for most intra-abdominal infections.

Antimicrobial effect of amniotic fluid against anaerobic bacteria

Amniotic fluid samples were obtained at term and tested for their antimicrobial effect on anaerobes, Peptostreptococcus (Ps.) anaerobius, Peptococcus (Pc.) prevotii, Bacteroides (B.) fragilis, and B. coagulans with facultative Escherichia (E.) coli serving as control. Amniotic fluid had only temporary bacteriostatic effect on Pc. prevotii and B. fragilis for 8 to 16 hours. This effect lasted for only 8 hours on Ps. anaerobius. On the contrary, the bacteriostatic effect of amniotic fluid was well sustained on E. coli and B. coagulans, lasting for the entire test periods of 20 and 32 hours, respectively. At the end of the time intervals mentioned, Ps. anaerobius, Pc. prevotii, and B. fragilis exhibited logarithmic growth, confirming the earlier reports that it is not nutritionally deficient. Amniotic fluid exhibited temporary bacteriostatic effect on Ps. anaerobius, P. prevotii, and B. fragilis, but this effect was well sustained against B. coagulans.

Efficacy of vancomycin and daptomycin against Staphylococcus aureus isolates collected over 29 years

We investigated vancomycin and daptomycin efficacy for Staphylococcus aureus isolates at our institution by testing 221 methicillin-sensitive and 299 methicillin-resistant isolates recovered from serious infections between 1979 and 2007 using a microdilution method. The MIC(90)s for vancomycin remained constant at 2 microg/mL for methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). For MSSA, the geometric mean vancomycin MICs remained at 1.1 microg/mL but varied from 1.1 to 1.7 for MRSA. Tolerance to vancomycin was seen in 6.5% of MRSA and 10.5% of MSSA. Daptomycin MIC(90)s remained at < or =1 microg/mL, and the daptomycin concentration at which 90% of the strains were killed (MBC(90)) remained at 2 microg/ml. Over 29 years, no trend was detected in vancomycin or daptomycin susceptibilities. Daptomycin had excellent inhibitory and bactericidal activities against all strains throughout the years. Although vancomycins inhibitory activity was consistent over time, vancomycin-tolerant strains whose presence was not predicted by their MIC were found.

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.

In Vitro Activities of Daptomycin, Ciprofloxacin, and Other Antimicrobial Agents against the Cells and Spores of Clinical Isolates of Bacillus Species

ABSTRACT Daptomycin inhibited 67 of 70 clinical isolates of Bacillus species at ≤1 μg/ml and 100% of them at ≤2 μg/ml. It showed bactericidal activity similar to that of ciprofloxacin against vegetative cells but not against spores. For 2 strains, the ciprofloxacin MICs were >4 g/ml, and 10 strains were resistant to erythromycin.

Comparative in vitro activities of ABT-773 against 362 clinical isolates of anaerobic bacteria.

ABSTRACT The activity of ABT-773, a novel ketolide antibiotic, against clinical isolates of anaerobic bacteria was determined and compared to the activities of other antimicrobial agents. MICs at which 90% of isolates were inhibited (MIC90s) were ≤0.06 μg/ml for Actinomyces spp., Clostridium perfringens, Peptostreptococcus spp.,Propionibacterium spp., and Porphyromonasspp. The MIC50s and MIC90s were ≤0.06 and >32 μg/ml, respectively, for Eubacterium spp.,Lactobacillus spp., Clostridium difficile, and Clostridium ramosum. The MIC90 for Bilophila wadsworthia,Bacteroides ureolyticus, and Campylobacter gracilis was 1 μg/ml, and that for Prevotella bivia and other Prevotella spp. was 0.5 μg/ml. The MIC90 for Fusobacterium nucleatum was 8 μg/ml, and that for Fusobacterium mortiferum and Fusobacterium varium was >32 μg/ml. The MIC90s for theBacteroides fragilis group were as follows: forB. fragilis, 8 μg/ml; for Bacteroides thetaiotaomicron, Bacteroides ovatus,Bacteroides distasonis, and Bacteroides uniformis, >32 μg/ml; and for Bacteroides vulgatus, 4 μg/ml. Telithromycin MICs for the B. fragilis group were usually 1 to 2 dilutions higher than ABT-773 MICs. For all strains, ABT-773 was more active than erythromycin by 4 or more dilutions, and for some strains this drug was more active than clindamycin.

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 drugs 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°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 A 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 μg/ml, 4.84 ± 6.15 μg/g, and 14.4 ± 22.84 μg/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<0.0001), peritoneal fluid concentration (r=‐0.783; p=0.0002), and appendix tissue concentration (r=‐0.704; p=0.0016) versus Δ time. There was a significant correlation between peritoneal fluid and plasma concentration (r=0.853; p<0.0001), and appendix tissue and plasma concentration (r=0.815; p=0.0001). These results indicate that tissue and peritoneal fluid concentrations are approximately 51% and 74%, respectively, of a simultaneous plasma sampling after approximately 5.8 hours.