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L C Preheim

Publications and source records attributed to L C Preheim.

At least 19 recordsLinked to original sources

Effect of cirrhosis on the production and efficacy of pneumococcal capsular antibody in a rat model.

We sought to study the immunogenicity of Type 3 pneumococcal capsular polysaccharide (PCP) antigen and the protective efficacy of Type 3 PCP antibodies in a rat model of cirrhosis. Cirrhosis with ascites was induced in male Sprague-Dawley rats by weekly gavage with CCl4. Cirrhotic and age-matched control rats were vaccinated with 25 micrograms of Type 3 PCP. Serum antibodies against Type 3 PCP were determined before vaccination and on postvaccination Days 5, 7, 10, 14, 21, 28, and 42 by radioimmunoassay. Maximum concentrations occurred at 7 days in cirrhotic rats and 10 to 14 days in control rats. Geometric mean Type 3 PCP antibody levels (ng AbN/ml) were higher in cirrhotic versus control rats before vaccination (75.9 versus 33.8; p = 0.011) and on post-vaccination Day 5 (626 versus 158; p = 0.008) and Day 7 (1,755 versus 493; p = 0.002). Postvaccination antibody from immunized control and cirrhotic animals provided passive immunity to Type 3 Streptococcus pneumoniae infection in mouse protection studies. Sham-immunized and PCP-immunized control and cirrhotic rats were challenged with 10(7) cfu Type 3 S. pneumoniae. Immunization was associated with a greater reduction in postchallenge mortality in control rats (91% reduced to 36%; p = 0.02) compared with cirrhotic rats (100% reduced to 83%; p = 1.0). Thus, the increased serum concentrations of functional, type-specific anticapsular antibody in vaccinated cirrhotic rats does not reverse their impaired resistance to Type 3 pneumococcal pneumonia.

Animals

Cirrhosis impairs serum bacteriostasis for Escherichia coli.

To study the effects of cirrhosis on serum inhibition of Escherichia coli, cirrhosis with ascites was induced in male Sprague-Dawley rats by intragastric administration of carbon tetrachloride. Heat-inactivated (56 degrees C for 30 minutes) serum from cirrhotic rats (CRS) or that from control rats (NRS) was inoculated with 1 x 10(5) colony-forming units per milliliter (CFU/ml) of E. coli, and growth was measured after 24 hours. The mean growth of E. coli in CRS was significantly higher than growth in NRS: 3.5 +/- 5.4 x 10(8) CFU/ml versus 1.2 +/- 2.0 x 10(6) CFU/ml, respectively (p < 0.01). Fifty-four percent of CRS samples (22/41) completely lacked bacteriostatic activity. These CRS samples were categorized as growth-supporting (G+CRS) because their growth exceeded the mean + 2 SD of NRS (5.2 x 10(6) CFU/ml). Serum bacteriostasis could be restored to G+CRS by adding purified rat apotransferrin (1 mg/ml), suggesting the presence of excess iron in G+CRS. However, serum iron concentration (SI) and total iron binding capacity (TIBC) were virtually the same in G+CRS (SI = 120 +/- 22 micrograms/dl; TIBC = 351 +/- 45 micrograms/dl) as in growth-inhibitory CRS (SI = 131 +/- 16 micrograms/dl; TIBC = 347 +/- 46 micrograms/dl) but were significantly less than NRS (SI = 208 +/- 29 micrograms/dl; TIBC = 533 +/- 57 micrograms/dl), p < 0.01. The percent transferrin saturation was similar in all groups: 34% +/- 6%; 38% +/- 5% and 39% +/- 9%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Pneumococcal pneumonia in a rat model of cirrhosis: effects of cirrhosis on pulmonary defense mechanisms against Streptococcus pneumoniae.

To study alterations in host defense mechanisms that enhance pneumococcal virulence, a model of Streptococcus pneumoniae pneumonia was developed in cirrhotic rats. Cirrhosis, with or without ascites, was produced in rats by intragastric administration of carbon tetrachloride (CCl4). Histopathologic and laboratory studies demonstrated that CCl4-induced cirrhosis was similar to alcoholic cirrhosis in humans. Cirrhotic rats were more susceptible to type 3 pneumococcal pneumonia induced by intratracheal challenge than controls, and the presence of ascites was associated with the lowest LD50. More cirrhotic rats with ascites had bacteremia and elevated levels of circulating capsular antigen after challenge compared with cirrhotic rats without ascites or controls. Pulmonary clearance of pneumococci was markedly reduced in rats with cirrhosis and ascites and was associated with reduced serum complement levels. This model may be useful in further studies of the pathogenesis and therapy of pneumococcal infections in the compromised host.

Animals

A model of pneumococcal pneumonia in chronically intoxicated rats.

To determine the role of chronic ethanol intoxication on the pathogenesis of pneumococcal pneumonia, male Sprague-Dawley rats were fed an ethanol-containing diet for 1 week before intratracheal challenge with type 3 Streptococcus pneumoniae and for 10 days after infection. Control rats were fed the same diet except that ethanol was replaced isocalorically with carbohydrate. Ethanol treatment increased pneumococcal bacteremia, levels of capsular polysaccharide antigenemia, and susceptibility to lethal pneumonia. Once dissemination occurred, ethanol-fed rats failed to eliminate pneumococci from the bloodstream. Ethanol-fed rats demonstrated a defect in late pulmonary clearance of pneumococci that was temporally associated with a significantly higher pneumonia severity index. Pneumonia was characterized by an intense polymorphonuclear leukocyte infiltration, severe edema, and a fibrous exudate. Bronchoalveolar lavage confirmed the heightened inflammatory response in the lungs of ethanol-fed rats, suggesting that chronic ethanol intoxication did not impair polymorphonuclear leukocyte recruitment but may alter their antipneumococcal functions.

Alcoholism

Pulmonary recruitment, adherence, and chemotaxis of neutrophils in a rat model of cirrhosis and pneumococcal pneumonia.

Cirrhotic rats have decreased pulmonary bactericidal activity and increased bacteremia after experimental pneumococcal pneumonia. To determine if this finding is due to impaired pulmonary recruitment of polymorphonuclear leukocytes (PMNL), bronchoalveolar lavage (BAL) was done on cirrhotic and normal rats after transtracheal challenge with pneumococcal types 3 and 1. Mean absolute numbers of recruited PMNL in BAL fluid (BALF) at 2, 4, 6, 8, and 24 h after 10(7) cfu of type 3 challenge were similar in cirrhotic and normal rats. In both groups, lower numbers of PMNL were recruited after challenge with 10(5) cfu of type 3. Type 1 pneumococci stimulated recruitment of similar mean absolute numbers of PMNL (x10(7] in BALF (cirrhotics vs. normals) at 24 h after challenges with 10(5) cfu (0.3 +/- 0.1 vs. 0.3 +/- 0.1) and 10(7) cfu (2.9 +/- 1.3 vs. 2.8 +/- 0.7). Peripheral blood PMNL from cirrhotic and normal rats did not differ in adherence to nylon wool columns or in chemotaxis toward lipopolysaccharide-activated normal rat serum. Thus the impaired pulmonary defense against pneumococcal pneumonia in cirrhosis is not due to deficient pulmonary PMNL recruitment.

Animals

High-pressure liquid chromatography and microbiological assay of serum ofloxacin levels in adults receiving intravenous and oral therapy for skin infections.

Thirty-two adults hospitalized with skin and skin structure infections received intravenous ofloxacin followed by oral ofloxacin. The standard treatment was 400 mg every 12 h. One patient with renal failure received 400 mg every 24 h. Serum ofloxacin levels were measured (1.5 h postdose and 1 h predose) during intravenous (32 patients) and oral (30 patients) therapy. Levels were assayed by high-pressure liquid chromatography (HPLC) and microbiological assay (MBA). Mean levels +/- standard deviation (in micrograms per milliliter) when measured by MBA after intravenous dosing were (postdose versus predose) 6.23 +/- 2.49 versus 2.42 +/- 1.56, and those after oral dosing were 6.17 +/- 3.25 versus 3.49 +/- 2.77. When measured by HPLC, mean levels +/- standard deviation after intravenous dosing were 5.81 +/- 2.08 versus 2.14 +/- 1.26 and those after oral dosing were 5.63 +/- 2.92 versus 3.41 +/- 2.98. There were no significant differences between levels achieved with oral or intravenous dosing when measured by either MBA or HPLC. Levels in serum did not correlate with side effects. The MICs for 50 and 90% of the 40 aerobic pathogens isolated from 21 patients were 0.5 and 2.0 micrograms/ml, respectively. Cure or improvement was achieved in 30 patients. Intravenous and oral administration of ofloxacin yielded similar levels in serum which were safe and effective in the therapy of skin infections in adult patients.

Administration, Oral

Pseudomonas pseudomallei, a common pathogen in Thailand that is resistant to the bactericidal effects of many antibiotics.

The purpose of this investigation was to identify newer antimicrobial agents that may be useful in the therapy of melioidosis. The in vitro susceptibilities of 199 clinical isolates of Pseudomonas pseudomallei to 22 antibiotics were determined by standard disk diffusion, and those to 13 antibiotics were determined by agar dilution. Over 90% of the isolates were susceptible to imipenem, piperacillin-tazobactam, piperacillin, ceftazidime, ticarcillin-clavulanate, ampicillin-sulbactam, and carumonam by both methods. Standard disk diffusion yielded unacceptably high false-susceptibility results with aztreonam, ciprofloxacin, and temafloxacin. Piperacillin, ceftazidime, imipenem, and ciprofloxacin were not bactericidal for three selected P. pseudomallei strains as determined by time-kill curve methods. Furthermore, addition of ciprofloxacin to piperacillin, ceftazidime, or imipenem did not enhance bactericidal activity. One hundred ninety-four strains showed weak beta-lactamase production that did not increase upon incubation with cefoxitin. These findings suggest that several newer antimicrobial agents may prove useful in the treatment of melioidosis. However, results of susceptibility studies involving P. pseudomallei and newer agents must be interpreted with caution.

Anti-Bacterial Agents

Isolation of Enterobacter aerogenes susceptible to beta-lactam antibiotics despite high level beta-lactamase production.

This report describes a patient with nosocomial meningitis from whom four distinct isolates of Enterobacter aerogenes were recovered over a complicated course of chemotherapy. The initial isolate was susceptible to expanded spectrum beta-lactams despite constitutive production of high levels of beta-lactamase. Resistant isolates recovered during antibiotic therapy had lost a 42,000 outer membrane protein. These data suggest that b-lactam susceptibility in the original isolate was due to "hyperpermeability" mediated by the 42,000 Dalton protein.

Anti-Bacterial Agents

Attempts to eradicate methicillin-resistant Staphylococcus aureus colonization with the use of trimethoprim-sulfamethoxazole, rifampin, and bacitracin.

Retrospective review of 197 patients with methicillin-resistant Staphylococcus aureus (MRSA) identified 47 in whom a regimen for eradication of MRSA colonization could be evaluated. The patients were elderly (mean age, 67.7 years), with 53% transferred from another institution and 53% treated in an intensive care unit. A mean of 47.1 days of hospitalization with an average of 4.9 antibiotics preceded the first MRSA culture. The usual regimen (mean, 6.0 days) was oral trimethoprim-sulfamethoxazole, 160/800 mg twice daily, oral rifampin, 600 mg once daily, and bacitracin ointment three times a day. Eradication succeeded in 40 patients, 9 relapsed, and MRSA persisted in 7. Twenty-four of 25 nares sites were cleared but only 16 of 22 other sites. MRSA infection eventually developed in 36%. No adverse reactions to the eradication regimen were noted. Although this treatment for MRSA carriage was safe and effective, decreased efficacy outside the nares and relapse limited its value.

Aged

Randomized, double-blind comparison of ciprofloxacin and trimethoprim-sulfamethoxazole for complicated urinary tract infections.

In a prospective, randomized, double-blind study, the effect of ciprofloxacin (250 mg orally, twice daily) was compared with that of trimethoprim-sulfamethoxazole (160 mg of trimethoprim and 800 mg of sulfamethoxazole orally, twice daily) on 45 patients with complicated urinary tract infections. Pretherapy isolates were all members of the family Enterobacteriaceae. Isolates were eradicated from 18 (82%) of 22 patients treated with ciprofloxacin and 12 (52%) of 23 patients treated with trimethoprim-sulfamethoxazole during and 5 to 9 days after therapy (P = 0.035). Both groups had similar relapse and reinfection rates at 4 to 6 weeks posttherapy. Adverse effects were mild and reversible, occurring in 1 of 22 in the ciprofloxacin group and 6 of 23 in the trimethoprim-sulfamethoxazole group. Disk diffusion susceptibility tests correlated better with broth macrodilution for ciprofloxacin than for trimethoprim-sulfamethoxazole. Ciprofloxacin is a safe, effective alternative to trimethoprim-sulfamethoxazole for the treatment of complicated urinary tract infections.

Ciprofloxacin

Oral ciprofloxacin therapy for chronic contiguous osteomyelitis caused by aerobic gram-negative bacilli.

Twenty adult patients with chronic contiguous osteomyelitis caused by aerobic gram-negative bacilli were enrolled in an open, prospective cooperative study to determine the effect of oral ciprofloxacin therapy in a dosage of 750 mg every 12 hours. There were 14 men and six women, with a mean age of 55 years. Fifteen of the 20 patients had undergone previous unsuccessful attempts at therapy; seven of the 20 patients had clinically important underlying diseases. Osteomyelitis involved the sternum in three patients and the bones of the lower extremity in 17 patients. Initial surgical debridement was performed in 15 of 20 patients. The predominant organism isolated was Pseudomonas aeruginosa, which was found as a single pathogen in 13 patients and as part of a polymicrobic flora in three patients. Based on posttreatment follow-up of seven to 21 months, clinical cure was achieved in 13 of 20 (65 percent) patients and bacteriologic cure was achieved in 14 of 20 (70 percent) patients. Minimal inhibitory concentrations of ciprofloxacin against P. aeruginosa increased during therapy in four of 16 (25 percent) patients. Minor gastrointestinal side effects occurred in five patients. Oral ciprofloxacin was an effective and safe therapy in patients with chronic contiguous osteomyelitis due to aerobic gram-negative bacilli.

Adult

Oral ciprofloxacin in the treatment of elderly patients with complicated urinary tract infections due to trimethoprim/sulfamethoxazole-resistant bacteria.

The effectiveness and safety of ciprofloxacin, a new quinolone antibiotic, were prospectively evaluated in the treatment of patients with complicated urinary tract infections caused by gram-negative organisms resistant to trimethoprim/sulfamethoxazole. Twenty-five elderly (mean age, 70.4 years) patients (24 men and one woman) were enrolled. Initial pathogens included Pseudomonas aeruginosa (15 isolates), Escherichia coli (five isolates), Enterobacter aerogenes (one isolate), Citrobacter freundii (one isolate), Serratia species (two isolates), Proteus vulgaris (one isolate), and enterococcus (one isolate). Patients received 500 mg of ciprofloxacin orally twice daily for one week (mean, 6.98 days). Results of urine cultures obtained during therapy were negative in all cases, and at one week post-therapy, 21 of 25 (84 percent) infections were cured. Four patients experienced a relapse with P. aeruginosa. Repeat urine culture specimens were obtained at four to six weeks from 14 patients who had cures at one week post-therapy, and seven continued to have cures. Three patients had late relapses with P. aeruginosa, E. coli, or Serratia marcescens, and four were reinfected with new strains. Five patients who received concomitant oral antacids had lower mean peak and trough serum ciprofloxacin levels than did patients not receiving antacids (p less than 0.05, Wilcoxon rank sum test). Mild adverse effects were seen in seven patients: eosinophilia (one patient), eosinophilia and reduced white blood cell count (one patient), crystalluria (one patient), granular casts (one patient), elevation of serum creatinine and blood urea nitrogen levels (one patient), and nausea (two patients), but none warranted discontinuation of ciprofloxacin therapy. P. aeruginosa isolates from two patients who experienced a relapse showed increases in minimal inhibitory concentrations from 0.13 to 0.5 and 2.0 micrograms/ml, respectively, to ciprofloxacin and other antibiotics. Orally administered ciprofloxacin was a safe and effective therapy for complicated urinary tract infections in elderly patients.

Administration, Oral

Methicillin-resistant Staphylococcus aureus in Veterans Administration Medical Centers.

To determine the frequency of isolation of methicillin-resistant Staphylococcus aureus (MRSA) at Veterans Administration Medical Centers, 163 hospitals were surveyed; 137 responded. Between 1975 and 1984, the number of Veterans Administration Medical Centers with known MRSA increased from 3 to 111. This increase was geographically widespread and occurred in hospitals of all sizes. In Veterans Administration Medical Centers, isolation policies for MRSA-infected patients were (% of hospitals using): strict (19%), contact (52%), site-related (28%), no isolation (1%). For patients colonized with MRSA policies were: strict (15%), contact (44%), site-related (35%), and no isolation (6%). Only 41% of Veterans Administration Medical Centers reported discharging known MRSA-colonized patients to nursing homes. Most attempts to eradicate MRSA carriage used trimethoprim-sulfamethoxazole plus rifampin with or without bacitracin ointment; success rates were low. MRSA incidence is increasing at Veterans Administration Medical Centers across the United States. Improved regimens to eliminate MRSA carriage are needed.

Cross Infection

Isolation and characterization of circulating immune complexes from patients with pneumococcal pneumonia.

Circulating immune complexes (CIC) were isolated from serum samples from patients with bacteremic and nonbacteremic pneumococcal pneumonia. Overall, 63% (26 of 41) of patients with pneumococcal pneumonia had elevated levels of immunoglobulin G (IgG)-containing CIC. IgM-containing CIC were identified in samples from only three patients. Serum samples from nonbacteremic patients contained significantly higher levels of IgG-containing CIC (96.6 +/- 111.7 micrograms/ml) than did samples from bacteremic patients (31.7 +/- 26.9 micrograms/ml) during week 1 in hospital (P less than 0.05). Immune complexes levels did not correlate with IgG concentrations in serum or anticapsular antibody levels. Immune complexes from nonbacteremic patients had sedimentation coefficients of greater than 19s by density gradient ultracentrifugation. In contrast, CIC from bacteremic patients had smaller coefficients, of between 9s and 14s. Pneumococcal capsular antigens were identified in concentrated dissociated CIC from both patient groups by counterimmunoelectrophoresis.

Animals

Antigen detection in the diagnosis and in the prognostic assessment of bacterial pneumonias.

Sputum cultures are not helpful in the immediate management of patients with bacterial pneumonia. Sputum Gram stains may provide a presumptive identification of an etiologic agent; this procedure, however, is insensitive (approximately 50%). Consequently, during the last decade, other more sensitive and specific methods of providing a rapid etiologic diagnosis have been sought. This article discusses data on antigen detection in various body fluids by counterimmunoelectrophoresis and agglutination tests. Results from our own laboratory as well as those reported in the literature are presented. The best estimates of antigen detection rates, by the most sensitive assays, in pneumococcal pneumonia, are as follows: serum, 45%-80%; urine, 50%-64%; and sputum, 75%-100%. There is less information for Haemophilus, Klebsiella, and Pseudomonas pneumonias, but the diagnostic yield is approximately 50%-100%. Data will also be presented on the association between free and complexed antigens and morbidity and mortality in pneumococcal pneumonia. Indicators of morbidity discussed include disseminated intravascular coagulation, duration and severity of illness, and occurrence of nephritis.

Adult