Comparison of the effect of three adrenal corticosteroids on human granulocyte function against Pseudomonas aeruginosa.

The effect of hydrocortisone, methylprednisolone, and dexamethasone on the phagocytic and bactericidal capabilities of normal human granulocytes (PMN) was studied under previously described optimal conditions for Pseudomonas aeruginosa, PA 1348A. At hydrocortisone and methylprednisolone concentrations of 1,000 micrograms/ml, delayed phagocytosis was clearly observed, whereas dexamethasone 400 micrograms/ml had no effect on phagocytosis. The bactericidal effect of PMN on PA 1348A was significantly reduced by all three corticosteroids at highest concentrations (p less than 0.05). However, the effect of methylprednisolone was greatest and that of dexamethasone was least evident, 25% and 10% reduction in PMN bactericidal activity, respectively. Following exposure to the highest concentrations of corticosteroids, TEM observations correlated well with the PMN functional assays. While the observations of PMN and bacteria in controls, hydrocortisone, and dexamethasone preparations were similar, evidence for incomplete phagocytosis, lack of vacuole coalescence, minimal disruption of bacterial cell walls, and dividing bacteria in phagosomes were evident in methylprednisolone preparations. These PMN functional and TEM observations suggest that of the three corticosteroids studied, methylprednisolone appears most deleterious to the PMN phagocytic and bactericidal activity.

Inhibitory and bactericidal activities of amifloxacin, a new quinolone carboxylic acid, compared with those of seven other antimicrobial agents.

The activity of amifloxacin, a new quinolone carboxylic acid compound, against 147 strains of microorganisms was studied and was compared with the activities of cinoxacin, trimethoprim, amikacin, and four beta-lactam antimicrobials. The minimal concentration at which 90% of strains were inhibited by amifloxacin was lowest for Escherichia coli and Klebsiella sp (less than or equal to 0.125 microgram/ml), followed by Proteus sp (less than or equal to 0.25 microgram/ml), Enterobacter sp and Citrobacter sp (less than or equal to 0.5 microgram/ml), Providencia sp (less than or equal to 2 micrograms/ml), and Pseudomonas aeruginosa, Serratia sp, and Acinetobacter calcoaceticus var anitratus (less than or equal to 8 micrograms/ml). When compared with the ranges of activity of seven reference antimicrobials, the range of amifloxacin activity was lowest for P aeruginosa, Citrobacter sp, Proteus sp, and A calcoaceticus var anitratus and similar to aztreonam's activity against Enterobacter sp. For amikacin-resistant P aeruginosa, the minimal inhibitory concentrations (MICs) of amifloxacin ranged from 1 to 16 micrograms/ml. The MICs and minimal bactericidal concentrations (MBCs) of amifloxacin were similar. For all strains tested, microbial susceptibilities to amifloxacin were greater than those to currently available oral antimicrobial drugs, such as cinoxacin and trimethoprim.

Moxalactam concentrations in human prostatic tissue.

The concentrations of moxalactam in human prostatic tissue, obtained by enucleation or transurethral resection, were measured in 10 patients after the intramuscular administration of two 500-mg doses. The average concentrations of moxalactam in prostatic tissue in the enucleated and transurethral resection specimens were 4.0 micrograms/g and 5.2 micrograms/ml, and the ratios of the moxalactam concentrations in prostate to those in plasma were 0.24 and 0.31, respectively. The concentrations of moxalactam achieved in prostatic tissue after the administration of relatively low doses were greater than the minimum inhibitory concentrations of moxalactam for most common gram-negative pathogens. Concentrations of moxalactam in carefully obtained transurethral resection specimens were similar to those found in the enucleated specimens.

Bacteremia following dental cleaning in patients with and without penicillin prophylaxis.

The rate, type, and magnitude of bacteremia were studied in 56 patients undergoing dental cleaning with and without penicillin prophylaxis. Sixty-one percent of patients without penicillin prophylaxis were bacteremic 5 minutes following the procedure. Although a significant decrease in detectable bacteremia occurred in patients receiving penicillin prophylaxis, the recovery of streptococci was not significantly different in the two groups. Using the present sample of patients as a basis for statistical inference, the true rate of bacteremia in such patients could be between 41% and 79% with 95% certainty. The magnitude of bacteremia was low and positive quantitative pour plates occurred at 5 minutes and only in patients without penicillin prophylaxis. Of the 71 total bacterial isolates, 53 (74.6%) were anaerobes and 18 (25.4%) were aerobes. This study indicates that parenteral penicillin prophylaxis for dental cleaning decreased detectable bacteremia rates significantly and could be recommended for patients with valvular heart disease who are known to be vulnerable to endocarditis.

In vitro comparison of N-formimidoyl thienamycin (MK0787) and Azlocillin with three aminoglycosides and ticarcillin against Pseudomonas aeruginosa.

The activities of N-formimidoyl thienamycin and azlocillin were compared with those of tobramycin, gentamicin, amikacin, and ticarcillin against 175 Pseudomonas aeruginosa isolates, including 24 strains with known mechanisms of resistance to aminoglycosides. The 50% mean inhibitory concentration for azlocillin was lower than for ticarcillin, but the 90% mean inhibitory concentration was similar for both drugs. All susceptible and multidrug-resistant strains were susceptible to N-formimidoyl thienamycin.

Pseudomonas aeruginosa: quantitation of maximum phagocytic and bactericidal capabilities of normal human granulocytes.

The maximum phagocytic and bactericidal capabilities of normal human PMNs against a seroresistant strain of Pseudomonas aeruginosa were evaluated by morphological observation, uptake of radiolabeled bacteria, and quantitative killing methods. The number of bacteria killed per PMN increased from 3 to 23 as the bacteria-to-PMN ratio was increased from 3:1 to 100:1. Conversely, the percent of bacteria killed decreased from 94% to 3%. In monolayers, an increase in the inoculum from 10(5) to 10(8) cfu/ml was associated with greater phagocytosis and a sixfold increase in PMNs containing greater than or equal to 5 bacteria/PMN. With the use of 75Se-labeled P. aeruginosa, optimal phagocytosis was observed with 10 to 20 bacteria/PMN in 20% NPS. Maximum uptake of 70% occurred in 40 min. No difference was observed in the uptakes of live or heat-killed bacteria. The maximum number of bacteria ingested per PMN was 32 +/- 5 at the highest ratio tested (100:1). The use of altered opsonic sources indicated the need for the classical complement pathway for optimal phagocytosis. Thus study describes the requirements and necessary standardization parameters that were found to be essential for a highly reproducible method for measuring phagocytosis and killing of P. aeruginosa by normal human PMNs. This method could be employed for clinical assessment of partial opsonic or PMN dysfunction in the study of the interaction of PMNs and P. aeruginosa.

Susceptibility of Pseudomonas aeruginosa to serum bactericidal activity. A comparison of three methods with clinical correlations.

Twenty-nine blood culture isolates of Pseudomonas aeruginosa were tested by three established methods to determine the effect of in vitro conditions on the survival of this organism in human serum. Clinical correlations were made to determine the relationship of serum resistance as defined by each method to clinical outcome. Major differences of bacterial survival in the presence of pooled normal human serum and in classification of isolates (sensitive, intermediate, resistant) were observed among the three methods. Isolates grown in broth for preparation of inocula demonstrated significantly greater sensitivity to serum bactericidal activity than those grown on agar. The use of organisms in early logarithmic growth phase or increased concentrations of serum augmented the serum sensitivity of these isolates. No correlation was observed between serum bactericidal activity and antibiotic susceptibility, pyocine type, patient mortality, or underlying disease. All strains of serotype 6 or 11 (immunotype 1 or 2) were serum-sensitive by one of the three methods. This study indicates that by testing isolates of P. aeruginosa under a variety of in vitro conditions, it is possible to identify a few isolates that are highly sensitive or resistant to serum under all conditions. The survival of the majority of strains of P. aeruginosa in human serum is highly dependent on in vitro conditions. Conclusions regarding the role of serum bactericidal activity in host defense must be drawn cautiously when based solely on in vitro tests.

Concentration of cefaclor in human prostatic tissue.

Concentration of cefaclor, a new oral cephalosporin, was measured in prostatic tissue of ten patients undergoing suprapubic prostatectomy. The average prostatic tissue concentrations were 0.51 +/- 0.22 microgram and 0.74 +/- 0.67 microgram per gram of tissue following the oral administration of 250-milligram and 500-milligram doses, respectively. The prostate/plasma ratios of cefaclor were approximately 0.7 indicating no evidence of accumulation of the drug in prostatic tissue. Levels of cefaclor achieved in human prostatic disease are equal to or less than the minimum inhibitory concentration of strains of known facultative bacterial pathogens associated with prostatitis.