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Biomedical subjects

C R Petzold

Publications and source records attributed to C R Petzold.

13 recordsLinked to original sources

Comparative bactericidal activities of ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin against Streptococcus pneumoniae in a dynamic in vitro model.

Several new quinolones that exhibit enhanced in vitro activity against Streptococcus pneumoniae have been developed. Using a dynamic in vitro model, we generated time-kill data for ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin against three isolates of quinolone-susceptible S. pneumoniae. Three pharmacokinetic profiles were simulated for each of the study agents (0.1, 1, and 10 times the area under the concentration-time curve [AUC]). Target 24-h AUCs were based upon human pharmacokinetic data resulting from the maximal daily doses of each agent. Ciprofloxacin was the least active agent against all three isolates. With regimens that simulated the human 24-h AUC, ciprofloxacin resulted in an initial, modest decline in the numbers of CFU per milliliter; however, by 48 h the numbers of CFU per milliliter returned to or exceeded the starting inoculum. At the AUC, levofloxacin resulted in variable bacteriostatic and bactericidal activities against the isolates. The remaining agents yielded bactericidal (99.9% reduction) activity by 48 h with regimens that simulated the AUC. At 0.1 time the AUC ciprofloxacin and levofloxacin produced no inhibitory effect, grepafloxacin exhibited bacteriostatic activity, trovafloxacin had mixed static and cidal activities, and clinafloxacin and moxifloxacin caused significant reductions in the numbers of CFU per milliliter by 48 h. All six agents produced cidal activity at 10 times the AUC. In this dynamic in vitro model of infection, the quinolones demonstrated various degrees of activity against S. pneumoniae. The rank order of activity, with respect to bactericidal effect, was ciprofloxacin (least active) << levofloxacin < grepafloxacin, trovafloxacin < clinafloxacin and moxifloxacin (most active). The rank order of the agents with respect to the selection of resistance was ciprofloxacin (most likely) > grepafloxacin, moxifloxacin, and trovafloxacin > levofloxacin > clinafloxacin.

Anti-Infective Agents↗

Methylcholanthrene causes increased thymocyte apoptosis.

The polycyclic aromatic hydrocarbon (PAH), methylcholanthrene (MCA), is a well studied carcinogen and a teratogen. MCA and other PAH cause immune suppression of B cell and T cell responses in mice and MCA had been reported to induce thymus atrophy. Here we show that MCA treatment causes thymus atrophy in adrenalectomized mice and in C57BL/6 and DBA/2 mice which differ in aryl hydrocarbon receptor (AhR) expression. This indicates that MCA-mediated thymus atrophy is mediated, at least in part, by glucocorticoid hormone receptor- and aryl hydrocarbon receptor-independent mechanisms. Assay of thymocytes, both in situ and ex vivo, demonstrate that MCA induces thymocyte apoptosis. Apoptotic thymocytes can be found within or adjacent to thymic Mphi, suggesting rapid phagocytosis. Mice that are deficient in tumor necrosis factor-alpha receptor-1 or p53, or that overexpress bcl-2 are susceptible to MCA-mediated thymus atrophy.

Animals↗

Comparison of single-dose cefmetazole and cefotetan prophylaxis in women undergoing primary caesarean section.

The efficacies of a single 2 g intra-operative iv dose of cefmetazole or cefotetan in women undergoing non-elective Caesarean section were compared. Thirty-six women (18 in each group) completed the double-blind protocol. Both antibiotics were equally effective as agents for prophylaxis of post-Caesarean infections. Combined data suggest that routine multi-dose antibiotic prophylaxis regimens could be replaced by a single dose regimen.

Adolescent↗

Comparison of cefotetan and cefoxitin as prophylaxis in cesarean section.

A study comparing the efficacy of cefotetan versus cefoxitin for prophylaxis in patients undergoing cesarean section was carried out at the University of Iowa. After institutional review, 36 subjects who met the study criteria and agreed to participate were entered into the study; of these, 29 were evaluable for efficacy. Twenty subjects received a single 2 gm dose of cefotetan, and nine subjects received three 2 gm doses each of cefoxitin. Both antibiotics were administered intravenously at the time the umbilical cord was clamped. The subsequent doses of cefoxitin were given intravenously at four and eight hours after the initial dose. Clinical and bacteriologic responses were evaluated; there were no statistically significant differences between the two groups, and both antibiotics provided effective prophylaxis against infection. It appears that cefotetan is a satisfactory antibiotic choice for cesarean section prophylaxis. Further, in this small study it appears that a single dose of cefotetan is as effective as three doses of cefoxitin. This implies that cefotetan would not only decrease administration time and supplies but would decrease the cost to the patient while maintaining very acceptable infection rates.

Adolescent↗

Ultrastructural alterations of term human amnionic epithelium following incubation with group B beta-hemolytic streptococci.

The association between the group B beta-hemolytic streptococcus (GBBHS) and premature labor, premature rupture of the membranes, and chorioamnionitis with intact membranes is well known. However, the mechanisms involved in this association remain unclear. In this study we incubated term chorioamniotic membranes from patients undergoing elective repeat cesarean section in double-armed incubation vessels that isolated the maternal from the fetal surfaces. The GBBHS was placed adjacent to the maternal surface and incubated for 2, 4, 8, 12, and 24 hr. Control membrane specimens from the same patient were incubated under identical conditions for identical time periods but without the presence of GBBHS. Examination of the specimens by transmission electron microscopy revealed progressive nuclear and basement membrane alteration in the study group that was maximal at 12 hr. There was also a progressive decrease in desmosome counts in the study membranes. These in vitro changes support the in vivo association of GBBHS with the aforementioned obstetric complications.

Amnion↗

Qualitative and quantitative changes of the vaginal microbial flora during the menstrual cycle.

Knowledge of the normal vaginal microbial flora is essential in understanding the etiology of female genital tract infections. This study was done to investigate both qualitative and quantitative differences that occur during the menstrual cycle. We studied 34 reproductive age women longitudinally. Quantitative cultures were obtained during menses and following the cessation of menses. A greater variety of organisms were found during menstruation. The effect was not selective with respect to aerobes or anaerobes. The total number of bacteria between the two culture periods did not change significantly.

Adult↗

Clindamycin levels in reproductive tissues.

Clindamycin is widely used in a variety of obstetric and gynecologic infections. Despite in vitro and clinical evidence of activity against anaerobes, genital organ tissue levels resulting from intravenous administration of the drug have not previously been reported. Following a single intravenous infusion of 600 mg of clindamycin phosphate, tissue levels were determined in operative specimens obtained from ten women. Specimens of cervix, uterus, fallopian tube, and ovary were obtained, and mean Clindamycin levels for each site were: cervix, 2.63 micrograms/ml; endometrium, 5.58 micrograms/ml; myometrium, 2.39 micrograms/ml; fallopian tube, 2.96 micrograms/ml; and ovary, 3.74 micrograms/ml. The mean serum level was 6.26 micrograms/ml at the time of uterine artery interruption. The clindamycin concentrations at all sites exceeded the usual therapeutic minimal inhibitory concentration, substantiating the usefulness of clindamycin in obstetric and gynecologic anaerobic infections.

Adult↗

Comparison of moxalactam and cefazolin as prophylactic antibiotics during cesarean section.

Prophylactic antibiotics have been shown to be effective in decreasing the incidence of febrile morbidity associated with cesarean section after labor. However, the relative effectiveness of different single antibiotics has been studied infrequently, and these investigations have been limited by small patient samples. Several new, broad-spectrum antibiotics are now available, and any further benefit from more traditional antibiotics for surgical prophylaxis remains untested. A randomized prospective double-blind therapeutic trial was therefore undertaken to compare the value of a first-generation cephalosporin (cefazolin) with a new third-generation cephalosporin (moxalactam). Between July 1981 and June 1983, 254 qualifying women who underwent primary cesarean section after labor were randomly chosen for either of the two treatment groups. Although not statistically significant, the rates of febrile morbidity, wound infection, and endometritis were less for those treated with cefazolin (4.0, 3.2, and 0.8%, respectively) than for those treated with moxalactam (9.2, 7.7, and 1.6%, respectively). No serious adverse effects were apparent in the mother and newborn infant from short-term exposure to either drug. Although the newer, more expensive, and broader-spectrum cephalosporin, moxalactam, was associated with a low postoperative febrile morbidity rate and short postpartum hospitalization, it was no more beneficial than cefazolin.

Anti-Bacterial Agents↗

Bacterial attachment to the chorioamniotic membranes.

Intra-amniotic infections are believed to result from bacteria of cervical and vaginal origin which gain access to the amniotic sac. The logical sequence in this process would be bacterial attachment to the maternal surface, followed by migration through the chorioamniotic membranes to the fetal surface. Fresh sterile chorioamniotic membranes were interposed between two arms of specially constructed incubation vessels. Bacteria (Escherichia coli, group B streptococci, or Neisseria gonorrhoeae) were inoculated into the arm (containing a basal salt medium) contiguous with the maternal surface. The arm contiguous with the fetal surface of the membrane contained pseudoamniotic fluid. At intervals up to 24 hours after inoculation, the membranes were removed, washed, fixed in glutaraldehyde, and examined by means of scanning and transmission electron microscopes. The ability of group B streptococci and E. coli to attach to and invade the chorioamniotic membranes was demonstrated by this technique. It appeared that group B streptococci had a greater capacity to attach and invade than did E. coli, whereas N. gonorrhoeae predictably failed to attach.

Bacterial Infections↗

Amniocentesis in the identification of inapparent infection in preterm patients with premature rupture of the membranes.

Twenty-nine preterm patients with premature rupture of the membranes who were not in labor and who did not have clinical chorioamnionitis underwent successful amniocenteses. Nine fluids were positive for bacteria. Subsequent clinical chorioamnionitis and shorter latency periods were more common in these 9 patients than in the 20 with sterile amniotic fluid. Positive fluids were more likely to be obtained from patients tapped within 48 hours of membrane rupture. In most patients with heavy bacterial growth, clinically apparent infection and/or labor soon supervened.

Amniocentesis↗

Effect of estrogen treatment on the genital tract flora of postmenopausal women.

The anaerobic and aerobic flora of the vagina was identified in 79 postmenopausal women, 33 of whom received estrogen replacement. Four anaerobic species were more prevalent among estrogen-treated women than among untreated women, whereas 2 anaerobic species were less prevalent in the treated group. The types of organisms isolated from both groups are similar and all organisms isolated were considered usual inhabitants of the genital tract.

Aged↗