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Biomedical subjects

D N Gerding

Publications and source records attributed to D N Gerding.

At least 163 records · Page 9Linked to original sources
PubMed1980

Failure of single doses of cefazolin and cefamandole to penetrate experimental chronic Escherichia coli abdominal abscesses.

Four perforated capsules were implanted into the abdominal cavity of each of three rabbits. After 4 to 5 weeks, single doses of cefazolin (30 mg/kg) or cefamandole (90 mg/kg) were administered intramuscularly. Peak levels of the respective drugs in serum were 104 +/- 10 and 127 +/- 5 micrograms/ml (mean +/- standard error); corresponding peak levels in capsule fluid were 6.3 +/- 2.3 micrograms/ml. Sixteen weeks after implantation, 2 X 10(6) colony-forming units of a strain of Escherichia coli susceptible to cefazolin (minimum inhibitory concentration, 1.0 microgram/ml) and cefamandole (minimum inhibitory concentration, less than 0.125 microgram/ml) was introduced into each of the 12 capsules. Chronic infection was established in seven of the capsules. At 4 to 6 weeks after infection, cefazolin and cefamandole were again administered. Peak serum concentrations were 102 +/- 3.3 micrograms/ml for cefazolin and 148 +/- 6.7 micrograms/ml for cefamandole. Peak concentrations in noninfected capsules were 7.5 +/- 3.4 and 12.1 +/- 2.1 micrograms/ml, respectively, not statistically different from the first study (P greater than 0.2). However, peak concentrations in infected capsules (less than 0.3 microgram/ml) were strikingly lower than in uninfected capsules (P less than 0.002). In keeping with the latter finding, quantitative cultures of E. coli in the infected capsules remained unchanged. Administration of [14C]cefamandole indicated that low drug levels were a result of poor drug penetration rather than drug inactivation or binding. Lack of vascularity and capsule wall necrosis may be responsible for poor drug penetration.

Abdomen↗
PubMed1979

Treatment of Pseudomonas endophthalmitis associated with prosthetic intraocular lens implantation.

Eight patients were treated for Pseudomonas endophthalmitis associated with the implantation of contaminated intraocular lenses. All patients showed clinical signs of infection (loss of red reflex, diminished visual acuity, and intraocular lens coagulum) and P. aeruginosa was isolated from vitreous aspirates and unused lenses of the same lot. Antibiotic treatment was initiated with systemic penicillin G, cephalothin, and chloramphenicol as well as subtenon-injected gentamicin. After identification of the organism, treatment was continued with systemic carbenicillin and gentamicin and subtenon-injected gentamicin. The intraocular lens was left in place for the first 48 hours of treatment in all eight patients. Five patients were successfully treated without removal of the intraocular lens and attained visual acuity of 6/6 (20/20) to 6/15 (20/50). Three patients (the two most seriously infected and one in whom antibiotics were discontinued) eventually lost their infected eye. Vitreous concentrations of gentamicin were good in one patient (1.7 micrograms/ml) and undetectable in another. Carbenicillin concentrations in vitreous (96 and 140 micrograms/ml) were high in two patients sampled. Endophthalmitis in the presence of a prosthetic intraocular lens can be successfully treated in some patients without removal of the prosthesis.

Anti-Bacterial Agents↗
PubMed1979

Nosocomial multiply resistant Klebsiella pneumoniae: epidemiology of an outbreak of apparent index case origin.

A nosocomial epidemic of multiply resistant (MR) Klebsiella pneumoniae characterized by resistance to gentamicin, tobramycin, kanamycin, cephalothin, chloramphenicol, and ampicillin occurred in a Veterans Administration hospital from 1975 to 1977. A total of 66 infected or colonized patients were observed in a 2-year period; there were 43 urinary tract infections, 13 wound or soft tissue infections, 8 pneumonias, and 6 patients with only asymptomatic stool colonization. Four patients had both pneumonia and a urinary tract infection. There were five secondary bacteremias. The majority of MR K. pneumoniae strains were type 30, but types 17, 21, and 23 and nontypable organisms were also recovered. Other gram-negative bacilli with the same antibiotic resistance pattern were isolated from 14 patients. Seven MR K. pneumoniae and three resistant Escherichia coli isolates were shown to transfer resistance to E. coli K-12. MR K. pneumoniae-infected patients were seriously ill, had long hospitalization times (mean, 67 days), and were in close geographic proximity to other cases. Compared with controls, cases more frequently had prior antibiotic treatment and urinary catheters, but not respiratory instrumentation, nasogastric tubes, or antacid treatment. The apparent source of the outbreak was traced to an index case who entered the hospital with an MR K. pneumoniae urinary tract infection. Asymptomatic gastrointestinal carriage without infection elsewhere was infrequent (1.6% of cultured patients), but 78% of patients with MR K. pneumoniae infections at other sites also had the organism in their stools. Hospital antibiotic usage was unchanged before and during the outbreak. The identification of an index case and relative lack of asymptomatic stool carriers are unique features of this plasmid-mediated MR K. pneumoniae epidemic. Although this MR K. pneumoniae outbreak appeared to be controlled by the use of isolation techniques, a simultaneous increase in gentamicin resistance among other gram-negative organisms was observed.

Anti-Bacterial Agents↗
PubMed1979

Physical characterization of ten R plasmids obtained from an outbreak of nosocomial Klebsiella pneumoniae infections.

Gentamicin resistance in Klebsiella pneumoniae involved in an outbreak at the Minneapolis Veterans Administration Hospital was due to a transmissible R plasmid. In addition to gentamicin, this plasmid conferred resistance to tobramycin, kanamycin, ampicillin, carbenicillin, cephalothin, chloramphenicol, and sulfathiazole. R plasmids which transferred this complex antibiogram were identified in several clinical isolates, including four different serotypes of K. pneumoniae, Escherichia coli, Enterobacter cloacae, and Proteus morganii. The covalently closed circular form of all R plasmids isolated had a sedimentation coefficient of 76S to 77S, corresponding to a molecular weight of 58 x 10(6). The possibility that a single R plasmid was responsible for the dissemination of multiple drug resistance among all of these different clinical strains was examined by characterizing the plasmids by using EcoRI restriction endonuclease. The same 15 fragments were obtained from each of the 10 plasmids analyzed. Their molecular weights ranged from 4 x 10(5) to 11 x 10(6). Thus, we conclude that each of the 10 plasmids present in the various clinical strains isolated from the hospital over a 7-month period originated from a common source and that R plasmid transfer was important in their spread.

Anti-Bacterial Agents↗
PubMed1979

Serious staphylococcal infections with strains tolerant to bactericidal antibiotics.

The clinical response in 20 cases of serious staphylococcal infection was compared with the in vitro resistance or "tolerance" of the infecting Staphylococcus to killing by antibiotics used in treatment. Cases were divided into two groups: (1) patients who initially received nonbactericidal antibiotics (ten cases), and (2) patients who initially received bactericidal antibiotics with or without nonbactericidal antibiotics. Mortality due to uncontrolled staphylococcal infection was 40% (4/10) in group 1 as compared with no mortality (1/10) in group0) in group 1 as compared with no mortality (0/10) in group 2. The duration of positive cultures after start of therapy in group 1 (mean, 6.1 days) was significantly longer than that in group 2 (mean, 1.3 days). The duration of fever after start of therapy in group 1 was not significantly different when compared with group 2.

Adult↗
PubMed1979

Staphylococcus aureus bacteriuria.

One hundred twenty-seven episodes of Staphylococcus aureus bacteriuria were reviewed retrospectively in two hospitals to establish the rate of occurrence, clinical importance, and associated predisposing factors. Staphylococcus aureus was an infrequent urinary isolate, and accounted for only about 1% of all positive urine cultures. Although almost all cases in a Veterans Hospital occurred in elderly men, episodes in a community hospital were observed in women and children as well. Patients usually had pyuria (71%) but only 39% had urinary symptoms of fever. Among predisposing factors, serious underlying diseases were uncommon, but urinary tract manipulations or abnormalities were present in nearly two thirds of patients. Fifty-five percent of cases were nosocomial, and 73% of these were associated with urinary catheterization or other invasive urinary tract procedures. Most patients (61%) were not treated for their bacteriuria, and there was a secondary bacteremia rate of 5.5% in the Veterans Hospital. Although infrequently encountered, the presence of S aureus in urine should be treated with at least as much concern as more frequently encountered bacteria.

Adolescent↗
PubMed1978

The association between Staphylococcus aureus bacteremia and bacteriuria.

The relationship between Staphylococcus aureus bacteremia and bacteriuria was studied over a five year period in three hospitals. In a Veterans Administration Hospital, 59 patients with Staph, aureus bacteremia had a urine culture within 48 hours of a positive blood culture. In 16 of 59 (27 per cent), greater than 10(5) Staph. aureus was recovered from the urine in pure culture. Six of these patients had apparent primary staphylococcal urinary tract infection. Clinical and laboratory parameters in the patients with staphylococcal bacteremia and bacteriuria were compared with those in 31 patients with staphylococcal bacteremia and sterile urine cultures. The two groups differed only in the more frequent occurrence of pyuria and proteinuria in the bacteriuric patients. In two other hospitals, staphylococcal bacteriuria occurred in 7 per cent of patients with Staph. aureus bacteremia and in 13 per cent of cases of staphylococcal endocarditis. Review of autopsy records for 33 patients who died within one month of their bacteremia failed to show a correlation between bacteriuria and the presence of renal abscess. Staphylococcal bacteriuria is a frequent and unexplained concomitant of Staph. aureus bactremia.

Abscess↗
PubMed1978

Interaction of cephalosporins with human and canine serum proteins.

The kinetic interaction of cephalothin and cefamandole with human serum protein and of cephalothin with canine serum protein was studied with use of a rate-of-dialysis method. Binding of antibiotic to serum proteins was complete in less than 1 min and was immediately reversible. Human serum bound 76.9% of cephalothin and 73.7% of cefamandole at 10 microgram/ml, and canine serum bound 41.3% of cephalothin at 10 microgram/ml when this technique was used. Quantitative binding determined by ultracentrifugation was 78.5% for cephalothin and 80.1% for cefamandole in human serum and 45.6% for cephalothin and 32.5% for cefazolin in canine serum. There was no delayed binding of these antibiotics to either human or canine serum. In addition, a large number of antibiotic-binding sites appeared to be present on both human and canine serum protein when the antibiotic concentration was increased to 10(5) microgram/ml.

Animals↗
PubMed1978

Prediction of the concentration of penicillins in ascitic fluid from serum kinetics and protein binding of the antibiotics in serum and ascitic fluid of dogs.

Ascites was induced in dogs by partial ligation of the inferior vena cava. Concentrations of ampicillin, penicillin G, oxacillin, cloxacillin, dicloxacillin, nafcillin, and methicillin in ascitic fluid and serum were each determined in three animals. All antibiotics were administered intramuscularly in a dose of 15 mg/kg (dry weight) for both single-dose and multiple-dose (eight doses at 4-hr intervals) studies. Binding of antibiotics to serum and ascitic fluid proteins was measured by ultracentrifugation. After single doses the highly protein-bound drugs (oxacillin, cloxacillin, dicloxacillin, and nafcillin) had lower percentages of penetration (ratio of peak in ascitic fluid to that in serum, multipled by 100) than did methicillin, ampicillin, and penicillin G, which have a lower degree of protein binding. The effect was partially overcome by repetitive doses, but five to six doses were usually required to reach equilibrium. In addition to protein binding, serum kinetics (particularly the log mean total concentration of drug in serum after multiple doses) were important determinants of antibiotic concentrations in ascitic fluid. The total antibiotic concentration in ascitic fluid at equilibrium can be accurately calculated from the log mean serum concnetration and the percentages of protein binding in serum and ascitic fluid.

Ampicillin↗
PubMed1978

Medium-dependent variation in bactericidal activity of antibiotics against susceptible Staphylococcus aureus.

Staphylococcus aureus resistant to bactericidal activity of antibiotics caused sepsis in three patients. Bacteriological and clinical responses were not achieved until serum and tissue fluid levels of administered antibiotics exceeded the minimum bactericidal concentration (MBC) of the infecting organism. Fifteen clinical isolates of S. aureus were tested in brain heart infusion broth and Mueller-Hinton broth for the MBC of gentamicin, vancomycin, clindamycin, oxacillin, cefazolin, and cephalothin. Results showed significant eightfold or greater broth-dependent differences in the MBC of at least one antibiotic against 87% (13/15) of strains tested. The MBC was unpredictable and varied with the strain, antibiotic, and medium used. No controlled studies are available to indicate the clinical significance of the MBC demonstrated in different media. The necessity for treating serious infection with bactericidal drugs has not yet been established; however, in septicemia such as that caused by bacterial endocarditis, bacteriostatic antibiotics have generally failed to eradicate the infection, whereas bactericidal agents have often been curative. Therefore, in patients unresponsive to usual antistaphylococcal therapy, we suggest that MBC testing be performed in at least two media and that treatment be instituted with antibiotics demonstrating the lowest MBC in all media used.

Anti-Bacterial Agents↗
PubMed1978

Ascitic fluid cephalosporin concentrations: influence of protein binding and serum pharmacokinetics.

Mongrel dogs with ascites created by inferior vena cava ligation were given cephalothin, cephaloridine, cefazolin, and cefamandole to evaluate the effect of protein binding and serum pharmacokinetics on the distribution of cephalosporins into ascitic fluid. Antibiotics were given intramuscularly (15 mg/kg) every 4 h for a total of eight doses. Antibiotic binding to dog serum and ascitic fluid was measured by ultracentrifugation. Binding of the cephalosporins to dog serum ranged from 31% for cephaloridine to 46% for cephalothin, considerably lower than human serum binding for cefazolin, cephalothin, and cefamandole. Antibiotic binding to ascitic fluid was only slightly lower than that to serum. Ascitic fluid antibiotic concentrations, which approached equilibrium at 16 to 28 h, were significantly higher for cefazolin and cephaloridine than for cephalothin and cefamandole. However, serum concentrations were also higher for cefazolin and cephaloridine, and percent penetration (ratio of serum peak to ascites peak x 100) was not statistically different among the four drugs. Binding of these cephalosporins to extravascular fluid protein was an important factor that determined the total ascitic fluid antibiotic level achieved. A formula utilizing the log mean serum level and binding to serum and extravascular fluid protein was used to accurately predict ascitic fluid drug levels at equilibrium.

Animals↗
PubMed1978

Prediction of cefazolin penetration in high- and low-protein-containing extravascular fluid: new method for performing simultaneous studies.

The effect of extravascular fluid protein concentration and drug-protein binding was studied in rabbits with subcutaneously implanted Visking chambers. Chambers containing serum or saline were simultaneously studied in three animals by injecting cefazolin (30 mg/kg) intramuscularly every 4 h for four doses. Five additional animals were then studied for an 8-h period while receiving two doses of cefazolin. Peak and trough serum and chamber fluid were assayed for cefazolin concentration. The three-animal experiment demonstrated that equilibrium in the subcutaneous chambers was reached after two intramuscular injections and that the extravascular fluid levels were stable in comparison to the wide fluctuation of the serum levels. The five-animal experiment demonstrated that after two doses the serum-filled chambers contained 12.9 mug of cefazolin per ml, whereas saline-filled chambers contained 1.8 mug of cefazolin per ml. Ratios of chamber to peak serum for the second study were 12.4% for serum chambers and 1.7% for saline chambers. The cefazolin concentration in high-and low-protein extravascular fluid in both studies could be predicted from the logarithmic mean of the peak and trough serum cefazolin concentration and the antibiotic binding to rabbit serum and extravascular fluid proteins. These observations explain the previously published apparent discrepancies seen in studies of extravascular penetration of highly protein-bound antibiotics such as cefazolin.

Animals↗
PubMed1978

Cavitary pneumonia associated with tularemia.

A wide range of microorganisms has been associated with cavitary pneumonia and pulmonary abscess. We present a case of serologically documented tularemia in an animal-hide handler who demonstrated multiple pulmonary infiltrates with cavitation. Inclusion of tularemia in the differential diagnosis of cavitary pneumonia in patients with exposure to animals is emphasized.

Adult↗
PubMed1977

Penetration of tobramycin into infected extravascular fluids and its therapeutic effectiveness.

The aminoglycoside antibiotic tobramycin was given intramuscularly to 15 patients with infected body fluids (empyema in five patients, peritonitis in five, peritonitis and empyema in one, tracheobronchitis in three, and infection of the pacemaker pocket in one). The infecting bacteria included Pseudomonas aeruginosa, Klebsiella, Enterobacter, Serratia, Escherichia coli, Proteus species, and Staphylococcus aureus. The mean dose of tobramycin was 1.7 mg/kg given intramuscularly every 8 hr for nine to 10 days. Levels of tobramycin in specimens of serum and infected body fluid obtained simultaneously were measured at various intervals after a dose of the antibiotic. Comparison was made between levels of tobramycin and minimal inhibitory concentrations (MICs) of the infecting bacteria. Bacteriological and clinical failures were common if the level in body fluid did not exceed the MIC. In patients with levels of tobramycin in body fluid that were higher than the MIC, cures were frequent. Drainage of infected body fluids is a necessary part of successful therapy of these infections.

Anti-Bacterial Agents↗
PubMed1977

Standardization of a preparative ultracentrifuge method for quantitative determination or protein binding of seven antibiotics.

A preparative ultracentrifuge method was standardized for determination of quantitative binding of cephalothin, cefamandole, cefazolin, cefaclor, erythromycin, gentamicin, and chloramphenicol to human serum proteins. At achievable in vivo concentrations, serum binding was 78.5% for cephalothin, 79.9% for cefamandole, 88.5% for cefazolin, 23.5% for cefaclor, 41.9% for erythromycin, 22.7% for gentamicin, and 59.5% for chloramphenicol. Techniques that use semipermeable cellophane or diaflow membranes, cross-linked dextran, inhibition of bacterial growth, protein precipitation, or liquid partitioning all have inherent problems with either the ligand or the antibiotic adversely interacting with the experimental apparatus. Ultracentrifugation provides a rapid, reproducible technique for protein-binding determinations of the classes of antibiotics described.

Anti-Bacterial Agents↗