Search PubMed⌕ Search

Biomedical subjects

D N Gerding

Publications and source records attributed to D N Gerding.

At least 127 records · Page 7Linked to original sources
PubMed1984

Effect of protein binding on simulated intravascular and extravascular kinetics of cefotaxime in an in vitro model.

The simulated intravascular and extravascular kinetics of cefotaxime were studied in an in vitro model to evaluate the effect of antibiotic protein binding in the "intravascular" and "extravascular" space. Intravascular fluid consisted of either phosphate-buffered saline, which has no cefotaxime binding, or 3% bovine albumin, which has 63% cefotaxime binding. Extravascular spaces were filled with phosphate-buffered saline, 1.5% bovine albumin (46.6% cefotaxime binding), or 3% bovine albumin. Cefotaxime (80 mg per dose) was infused every 3 h for eight doses, and intravascular and extravascular drug concentrations were measured after doses one and eight. The corresponding intravascular and extravascular spaces were at (phosphate-buffered saline) or approaching (3% bovine albumin) equilibrium by dose eight. There were marked differences in drug concentrations achieved in the various extravascular spaces, but all could be explained on the basis of differing amounts of albumin present and the resultant differences in cefotaxime binding.

Cefotaxime↗
PubMed1984

Comparison of azlocillin, ceftizoxime, cefoxitin, and amikacin alone and in combination against Pseudomonas aeruginosa in a neutropenic-site rabbit model.

The efficacy of beta-lactam antibiotics and amikacin alone and in various combinations against Pseudomonas aeruginosa was studied in a rabbit model simulating a closed-space infection in a locally neutropenic site. Six strains of P. aeruginosa were studied in semipermeable chambers placed subcutaneously in rabbits. Therapy was begun 4 h after inoculation of 5 X 10(4) CFU of bacteria per ml of pooled rabbit serum into the chambers. Antibiotics were administered intramuscularly every 6 h for 16 doses. Quantitative bacteriology was measured at the start of therapy and at 20, 44, and 92 h thereafter. Antibiotic concentrations were measured in blood and chamber fluid. Results were compared with in vitro tests of susceptibility and synergy. No single-agent therapy eradicated any of the six test organisms. Azlocillin (100 mg/kg per dose) plus amikacin (20 mg/kg per dose) eliminated five of six organisms by 92 h, and ceftizoxime (100 mg/kg per dose) plus amikacin (20 mg/kg per dose) eliminated three of six test strains. Azlocillin plus ceftizoxime (each 100 mg/kg per dose) failed to eliminate any of the six strains. To eliminate P. aeruginosa in this model, two drugs were required, with one being an aminoglycoside. In vitro susceptibility tests of synergy were predictive of successful therapy whenever the antibiotic concentrations (free and total) at the infection site exceeded the MBC for both the aminoglycoside alone and the beta-lactam when tested in combination with amikacin.

Agranulocytosis↗
PubMed1984

In vitro activities of amphotericin B in combination with four antifungal agents and rifampin against Aspergillus spp.

Strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were tested for in vitro susceptibility with a microtiter plate system in buffered yeast-nitrogen base and in buffered minimal essential medium. Isolates were tested against amphotericin B, flucytosine, rifampin, ketoconazole, ICI 153,066, and Bay n 7133 and against combinations of amphotericin B with each of the other five drugs. Combinations of amphotericin B and rifampin were the most active against all three species of Aspergillus. Flucytosine combined with amphotericin B produced little or no reduction of the MICs at which 90% of the strains were inhibited compared with amphotericin B alone. With one exception, the addition of ketoconazole, ICI 153,066, or Bay n 7133 to amphotericin B did not consistently alter the MICs. The addition of ICI 153,066 markedly increased the MICs of amphotericin B against the A. flavus isolates in both media. When the azoles were tested alone, Bay n 7133 was the most active against A. fumigatus, but was two- to fivefold less active against A. flavus. Ketoconazole was the most active azole against A. flavus.

Amphotericin B↗
PubMed1984

MBCs for Staphylococcus aureus as determined by macrodilution and microdilution techniques.

MBC testing of clindamycin, methicillin, cephalothin, gentamicin, and vancomycin with 67 clinical isolates of Staphylococcus aureus was examined by both standard macrodilution tubes and commercial microdilution trays. Standard macrodilution failed to give reproducible (99.9% killing) MBC results, even when a strictly defined protocol was followed. Continuous shaking during incubation resulted in regrowth of more colonies than did stationary incubation. Vortexing of incubated tubes before subculture resulted in regrowth of more colonies than did careful transfer of the contents to sterile tubes before vortexing and subculture. No significant difference in MBCs was demonstrated by the use of log-phase versus stationary-phase inocula. Use of the multiprong inoculator for subculture from commercial microdilution trays was unsatisfactory because, although antibiotics evaluated were inactivated by subculture to a pH 5.5 agar plate coated with a beta-lactamase solution, the volume of broth transferred by the prongs was small and inconsistent, ranging from 0 to 3 microliter. Subcultures of commercial microdilution panels with a 1-microliter loop, 10-microliter pipette, and 100-microliter pipette were also evaluated. Results of MBC testing were most reproducible when the entire 100-microliter volume was aspirated from commercial microdilution wells after stirring and the contents of each well were spread over a separate sheep blood agar plate.

Anti-Bacterial Agents↗
PubMed1984

In vitro activities of ureidopenicillins alone and in combination with amikacin and three cephalosporin antibiotics.

The MIC and MBC activity of mezlocillin alone and in combination with two concentrations of ceftizoxime, moxalactam, and amikacin and a single concentration of cefoxitin was studied in a broth microdilution partial checkerboard against 472 strains of aerobic gram-negative and gram-positive bacteria. Azlocillin was tested alone and in the same combinations against Pseudomonas aeruginosa. Of the gram-negative bacilli tested, 38% were gentamicin resistant. Antagonism (less than or equal to a fourfold ureidopenicillin MIC increase) was observed frequently with combinations of ureidopenicillins plus cefoxitin and sporadically with ureidopenicillins plus ceftizoxime or moxalactam. Partial synergism (less than or equal to a fourfold ureidopenicillin MIC decrease) was evident with both combinations of ureidopenicillins plus amikacin and ureidopenicillins plus ceftizoxime or moxalactam, the percentage being dependent upon the individual species and combinations.

Amikacin↗
PubMed1984

Enhancement of the in vitro activity of amphotericin B against Aspergillus spp. by tetracycline analogs.

Strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were tested for in vitro susceptibility to amphotericin B alone and in combination with fixed concentrations of tetracycline, doxycycline, or minocycline, using buffered minimal essential medium in microtiter plates. Enhanced inhibitory activity was seen, especially with combinations of amphotericin B and minocycline. Synergistic activity between amphotericin B and minocycline was observed in each of five isolates of each species when tested in a checkerboard dilution scheme. Time-kill curves demonstrated killing an A. fumigatus isolated at concentrations of amphotericin B that were four- or eightfold lower in the presence of 5 or 15 micrograms of minocycline per ml than with amphotericin B alone. Of the tetracycline analogs tested, minocycline has the greatest activity against A. fumigatus, A. flavus, and A. niger conidia when potentiated by amphotericin B.

Amphotericin B↗
PubMed1984

Ciprofloxacin penetration into extravascular spaces in a rabbit model.

Ciprofloxacin penetration into extravascular spaces was studied in a rabbit Visking chamber model. The drug was administered (7 mg/kg) intramuscularly every 4 h for eight doses. Peak and trough drug levels by dose 8 were 1.3 and 0.35 micrograms/ml in serum and 0.61 and 0.50 micrograms/ml in extravascular sites. The ratio of extravascular site to serum free drug area under the drug curve by dose 8 was 91.1%. This potent, new antimicrobial agent appears to distribute freely to extravascular spaces in this animal model.

Animals↗
PubMed1984

Evaluation of the 24-h API 20A anaerobe system for identification of Clostridium difficile.

Accurate identification of Clostridium difficile is important when antibiotic-associated diarrhea or pseudomembranous colitis is suspected. Presumptive identification of C. difficile was made on the basis of microscopic features and colony characteristics on cycloserine, cefoxitin, fructose, and egg yolk agar medium. We studied the reliability of the 24-h API 20A anaerobe system for definitive identification of C. difficile. This system showed low dependability after the recommended 24 h of incubation by confirming the identity of only 54% of the isolates presumptively identified as C. difficile. There was a marked improvement in the system's capability after 48 h of incubation, when the identity of 95% of the isolates was confirmed.

Anaerobiosis↗
PubMed1984

Evaluation of new blood culture processing systems.

The Antimicrobial Removal Device (ARD; Marion Scientific) was evaluated in vitro with simulated blood culture samples in fresh blood and clinically with samples from potentially septic patients to test its ability to remove antimicrobial agents and recover bacteria from blood culture specimens containing these drugs. In simulated specimens, the ARD was evaluated for adverse affects on microorganisms as well as compared with lysis-centrifugation (Isolator; Du Pont Co.), biphasic brain heart infusion bottles, and tryptic soy broth bottles for antimicrobial inactivation and organism recovery. There was no adverse effect of the ARD on organisms during a 4-h test period. The ARD was the only system to actually inactivate antimicrobial agents and removed greater than 99.2% of all antimicrobial agents tested from spiked and clinical specimens. Overall, with simulated blood culture specimens, the ARD recovered 90% of bacteria spiked into fresh blood containing antimicrobial agents, Isolator recovered 73%, biphasic brain heart infusion bottles recovered 31%, and tryptic soy broth bottles recovered 24%. In the clinical study, 43 of 86 clinically significant isolates were recovered only by ARD-assisted processing, 6 were recovered only by conventional processing, and 37 were recovered by both methods (the advantage of ARD processing over conventional processing in the clinical study was significant at P less than 0.001). Both clinical and simulated specimens demonstrated the ARD-associated blood culture processing to be the most efficient method for the isolation of microorganisms from specimens containing antimicrobial agents.

Anti-Bacterial Agents↗
PubMed1983

Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis.

101 patients with Clostridium-difficile-associated diarrhoea or colitis were prospectively randomised to 10-day oral courses of metronidazole, 250 mg four times a day, or vancomycin, 500 mg four times a day. 7 did not complete the protocol and were dropped from analysis. Pseudomembranous colitis (PMC) was diagnosed after endoscopy in 33 patients. Of the remaining patients without PMC, 38 had both C difficile culture and cytotoxin and 23 had only culture evidence of C difficile. 52 evaluable patients received vancomycin and 42 received metronidazole. There were two treatment failures with metronidazole and none with vancomycin (p = 0.20); and two relapses with metronidazole versus six with vancomycin (p = 0.17). Treatment in 1 patient in each group was discontinued because of drug intolerance. Response and relapse rates of the 33 patients with PMC were no different from those of the remaining patients. Pharmacy cost for the dosage used was $387.48 to $520.00 for vancomycin and $11.84 for metronidazole. Metronidazole and vancomycin have equivalent efficacy and relapse rates and are tolerated to a similar extent by patients with C-difficile-related diarrhoea and colitis, but metronidazole is considerably more economical.

Adult↗
PubMed1983

Influenza B: hospital activity during a community epidemic.

During a community epidemic of influenza B, surveillance throat cultures for influenza were collected from febrile adult patients and hospital employees on three medical wards to determine the frequency and source of influenza among hospitalized patients. Twenty-five cases of influenza B (18.5% of febrile patients) were identified; no clusters of influenza-like illness occurred. The attack rate on two wards was 4.6%. Peak hospital influenza incidence followed that in the community by 1-2 weeks. Twelve of the cases were community-acquired and 13 were nosocomial. 75% of community-acquired cases had three or more common influenza B symptoms, compared with only 39% of nosocomial cases. A viral etiology of fever was suspected clinically in one-half of the cases, but influenza was specifically suspected in only one case. Two ill culture-positive nurses were identified on the job but no asymptomatic carriers were found among ward personnel. We conclude that influenza B cases were present among hospitalized patients in the absence of recognizable clusters of disease and that patients with community-acquired illness as well as nursing personnel may have introduced influenza into the hospital. Influenza B may be difficult to diagnose clinically in hospitalized patients, but viral throat cultures performed in all suspected cases should identify many infected patients.

Adult↗
PubMed1983

Improved recovery of microorganisms from patients receiving antibiotics with the antimicrobial removal device.

Three hundred thirty-seven paired sets of blood cultures and ten sets of body fluid cultures from patients receiving antimicrobials were processed simultaneously by conventional methods with and without the use of an antimicrobial removal device (ARD) over a 13-month period of time in order to compare recovery rates. Forty-two significant pathogens were recovered: 19 by ARD processing only, four by conventional testing only, and the remaining 19 by both methods of processing. (P less than 0.001). Seventeen patient samples contained antimicrobics not active against the blood isolate (mainly Candida albicans). There was no difference (P greater than 0.1) between ARD-assisted and conventional methods in rate (frequency of cultures that were ultimately positive) or rapidity of detection of these microorganisms. In 17 subjects receiving antimicrobials active, in vitro, against the isolated microorganism, use of the ARD displayed a superior rate of recovery compared with conventional processing (P less than 0.001) and more rapidly detected organisms found both with and without ARD processing (P less than 0.04). Contamination rate was 3.7% for use of ARD compared with 0.6% without ARD (P less than 0.01). The ARD is a useful addition to conventional blood culture processing when used in a population of patients already receiving antimicrobial agents.

Adult↗
PubMed1983

Comparison study of the kinetics of ceftizoxime penetration into extravascular spaces with known surface area/volume ratio in vitro and in vivo in rabbits.

The extravascular kinetics of ceftizoxime were studied both in an in vitro kinetic model and in an in vivo rabbit model. Visking tubing chambers were used in both models to provide extravascular spaces with large or small volumes and surface areas, but identical surface area/volume ratios. Four rabbits, each implanted with two large Visking chambers and four small chambers, received 50 mg of ceftizoxime per kg intramuscularly every 3 h for eight doses. In the in vitro model, 80 mg of ceftizoxime was infused over 30 min every 3 h for eight doses. Intravascular and extravascular spaces were sampled in both models after the eighth dose. Ceftizoxime had similar intravascular kinetics in both models, i.e., the peak levels, the peak-to-trough fluctuations, and the half-life were comparable. The area under the curve (AUC) for the extravascular spaces was also similar in the two models. Large and small chambers having identical surface area/volume ratios demonstrated identical kinetics. The extravascular Visking chamber spaces achieved equilibrium with the intravascular spaces in both models, i.e., the AUC for the extravascular spaces was the same (P > 0.2) as that for the serum (rabbit model) or the test chamber (in vitro model). This study illustrates (i) that our modified in vitro model is a potentially valid model for studying extravascular kinetics; (ii) that extravascular spaces with identical surface area/volume ratios show similar penetration kinetics with a freely diffusible drug, such as ceftizoxime, despite differences in size; and (iii) that the Visking chamber extravascular-space model permits the free diffusion of the antimicrobial agent and reaches equilibrium (equivalent AUC) with the intravascular space.

Animals↗
PubMed1983

Extravascular penetration of tobramycin and netilmicin in a subcutaneous visking chamber model in rabbits.

Netilmicin and tobramycin penetration in a rabbit Visking chamber model was studied after administration of multiple intramuscular doses of 2 mg of either drug per kg every 4 h in a double-crossover design. The mean serum half-life, mean peak concentration in serum, and mean area under the plasma concentration curve were similar. The mean peak concentration in the chamber and mean area under the plasma concentration curve were likewise not significantly different.

Animals↗
PubMed1983

Prospective study of gram-stained stool smears in diagnosis of Clostridium difficile colitis.

Gram stains of stools from patients with diarrhea and control patients with no diarrhea were examined for a predominance of gram-positive rods and the presence of polymorphonuclear leukocytes. Results were compared with those from lower gastrointestinal endoscopy for pseudomembranes. Clostridium difficile culturing, and C. difficile toxin assay. The Gram stain was moderately difficult to interpret and was not useful in diagnosing diarrheal disease associated with C. difficile.

Clostridium Infections↗
PubMed1983

Fungal meningitis manifesting as hydrocephalus.

Four patients with fungal meningitis and hydrocephalus were treated by placement of intraventricular shunts prior to the diagnosis of infection. As a consequence, they were subjected to the risks of surgery as well as to shunt suprainfection. We suggest that chronic meningitis be ruled out in all patients prior to placement of shunts. Preoperative evaluation should include the examination of cisternal or ventricular CSF when a lumbar CSF specimen is nondiagnositc. When fungal meningitis is present, a course of amphotericin B should be initiated and the CSF sterilized prior to the placement of the permanent extracranial shunt. Where acute hydrocephalus supervenes, temporary ventricular drainage may be employed. In some cases of fungal meningitis, the symptoms of hydrocephalus will be resolved with antifungal therapy alone, obviating the need for ventricular decompression.

Adult↗