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Biomedical subjects

B Kemmerich

Publications and source records attributed to B Kemmerich.

At least 19 recordsLinked to original sources

Systemic and endotracheal antibiotic prophylaxis of nosocomial pneumonia in ICU.

Nosocomial pneumonias, especially in ventilated patients, are a continuing problem in modern medicine. Pathogens most commonly involved with these pneumonias are Enterobacteriaceae, Ps. aeruginosa and S. aureus. Several prevention measures for nosocomial pneumonia are possible such as parenteral and topical antibiotics--a very controversial issue. Several studies with parenteral antibiotics, starting as early as 1954, could not prove any benefit of parenteral antibiotics in pneumonia prevention. Topical antibiotics, starting with polymyxin or gentamicin via the endotracheal tube in the 70s, gave controversial results. In a prospective, randomized, double-blind placebo controlled study with gentamicin via the endotracheal tube in ventilated ICU patients we found no significant reduction of pneumonia rate and mortality. However, the combined approach (SDD) of oropharyngeal, gastrointestinal and parenteral use of certain antibiotics appears to give promising results in specific patient subgroups such as ventilated polytrauma patients in ICU.

Administration, Topical↗

[Value of diagnostic procedures in fiberoptic bronchoscopy of pulmonary infections].

Fibreoptic bronchoscopy has become an important means of diagnosing infections of the lower respiratory tract, since it a method with few complications, whereas, on the other hand, the conventional non-invasive methods are hardly reliable in respect of diagnostic relevance. Frequent oropharyngeal contamination severely limits the significant assessment of the pathogenicity of cultured microorganisms. The protected specimen brush (PSB) or quantitative cultures of bronchoalveolar lavage (BAL) might be useful in solving this problem. These methods were studied in two prospective trials comprising 123 patients with suspected bronchopulmonary infection and 54 control patients. Both methods were found to be disappointing in respect of sensitivity; moreover, quantitative cultivation did not yield any differences with regard to specificity.

Bacterial Infections↗

[Community-acquired pneumonia].

In a prospective study 212 patients were analysed who, between 1. 10. 1982-31.12. 1983 and 1. 10. 1985-31. 12. 1986, had been admitted to hospital because of pneumonia. The causative organism was identified in 127 of the 212 patients (60%). Pneumococcus was the most common organism (n = 64), as demonstrated by culture and immunological techniques of determining antigen or antibody. Next most common was Legionella (n = 15) of various species. Mixed infections were found in 11 patients, in all instances associated with pneumococci. There were 24 deaths (11.3%). It is concluded from these results that (1) determination of pneumococcal antigen in sputum, but not in urine or serum, can improve the identification of the causative organism; (2) Legionella is one of the most common causes of pneumonia acquired outside of hospital; and (3) adequate serological diagnosis of Legionnaire's disease is possible only if a large number of different species are tested for.

Adolescent↗

Different calcium and oxidative metabolic responses in human blood monocytes during exposure to various agonists.

It has become increasingly apparent that certain agonists of phagocytic cells exert their effects by using calcium as an intracellular messenger. Most studies have employed neutrophils for such analyses. We have investigated the requirement of calcium for respiratory burst activation in human blood monocytes by using three triggering agents, concanavalin A (Con A), N-formyl-methionyl-leucil-phenylalanine (FMLP), and phorbol myristate acetate (PMA). There was no overall correlation between the maximal extent of transient rise in cytosolic-free calcium (FMLP greater than Con A greater than PMA) and superoxide (O2-) release (PMA greater than Con A greater than FMLP). PMA, as the most effective agonist of respiratory burst activity, neither increased ionized cytosolic calcium [Ca2+]i nor plasma membrane 45Ca2+ permeability. FMLP evoked increments in [Ca2+]i occurred at lower concentrations than did respiratory burst activation, whereas with Con A a rise in [Ca2+]i and O2- release were parallel. Intracellular Ca2+ release into cytosol was blocked by 8-(N,N-diethylamino)octyl-3,4,5-trimethoxy benzoate, HCl (TMB-8). This caused a parallel inhibition of Con A or FMLP elicited [Ca2+]i transients and O2- release, while burst activity stimulated by PMA was unaffected. Our data thus suggest that a transient rise in [Ca2+]i is essential for Con A and FMLP activation in human blood monocytes. In addition to the calcium signal, other intracellular messengers are required for FMLP stimulation. Respiratory burst activation by PMA appears to act independently of [Ca2+]i transients.

Calcium↗

Significance of non-pneumophila Legionella species in adult community-acquired and nosocomial pneumonias.

The number of different Legionella species is increasing at an impressive rate. In two prospective studies, one involving 110 intensive-care unit (ICU) patients with mainly nosocomial pneumonias and the other 105 patients with community-acquired pneumonias, we investigated the incidence and significance of Legionella pneumophila and non-pneumophila pneumonias on the basis of 17 different main serogroups. In the first study, 14 ICU patients had 15 (13.6%) Legionella pneumonias, which, in 5 cases (33%), were of non-pneumophila etiology. In the second study, 9 patients with community-acquired pneumonias had 10 (9.5%) Legionella pneumonias. Leading this study were 6 L. gormanii infections, followed by 2 L. dumoffii and only 1 L. pneumophila and 1 L. longbeachae pneumonia. Of the total, 22 of 23 patients with Legionnaires' disease suffered from severe basic diseases and complications (acute renal failure, respiratory insufficiency, etc.) predominant among the nosocomial pneumonias. The mortality rate was significant in these patients at 33% (5 patients) in the ICU group and 10% (1 patient) in the group with community-acquired pneumonias. We conclude that non-pneumophila Legionella species should receive more diagnostic and therapeutic consideration in patients with nosocomial or community-acquired pneumonias.

Adolescent↗

Comparative efficacies of ciprofloxacin, ampicillin and chloramphenicol in treatment of experimental Haemophilus influenzae pneumonia.

An experimental murine model of bacteraemic Haemophilus influenzae pneumonia was used to evaluate the therapeutic efficacy of ciprofloxacin, as compared with ampicillin and chloramphenicol. An ampicillin-sensitive (AS) and an ampicillin-resistant (AR) challenge strain were employed. Ciprofloxacin treatment produced intrapulmonary killing of H. influenzae which was superior to that achieved with ampicillin (P less than 0.001, both strains) and chloramphenicol (P less than 0.001, strain AS; P less than 0.005, strain AR). Likewise, survival from strain AS pneumonia was 61% in the ciprofloxacin-treated animals, as compared with 43% for the chloramphenicol-treated, and 22% for the ampicillin-treated groups. We conclude that ciprofloxacin may be an effective agent in treating pneumonia caused by either ampicillin-sensitive or ampicillin-resistant strains of H. influenzae.

Ampicillin↗

Comparative evaluation of enoxacin, ofloxacin, ampicillin, and chloramphenicol for treatment of experimental Haemophilus influenzae pneumonia.

A murine model of bacteremic Haemophilus influenzae type b pneumonia was used to evaluate the therapeutic efficacies of the quinolone antimicrobial agents enoxacin and ofloxacin compared with those of ampicillin and chloramphenicol. Ampicillin-susceptible (AS) and ampicillin-resistant (AR) challenge strains were employed. Treatment with enoxacin or ofloxacin produced intrapulmonary killing of H. influenzae that was superior to that achieved with ampicillin (P less than 0.01 to P less than 0.001 for both AS and AR strains). Ofloxacin and enoxacin also provided killing greater than that with chloramphenicol for the AS strain (P less than 0.01 to P less than 0.001). For the AR strain, ofloxacin provided killing greater than that obtained with chloramphenicol (P less than 0.001). Survival from AS strain pneumonia was 60% in enoxacin-treated and 78% in ofloxacin-treated animals compared with 41% for chloramphenicol-treated and 23% for ampicillin-treated groups. We conclude that enoxacin and ofloxacin may be effective antimicrobial agents in treating either AS or AR strains causing H. influenzae pneumonia.

Ampicillin↗

Comparative oxidative microbicidal activity of human blood monocytes and alveolar macrophages and activation by recombinant gamma interferon.

The relative oxidative and microbicidal activities of human blood monocytes compared with those of alveolar macrophages (AM) are poorly defined. Furthermore, the comparative efficiency of recombinant gamma interferon (rIFN gamma) to enhance microbicidal function of these 2 cell populations is uncertain. In this study, blood monocytes and AM were obtained concomitantly from 10 healthy, nonsmoking human subjects. Cells were adjusted to equivalent cell concentrations and assayed for respiratory burst activity (superoxide anion production) during soluble (Concanavalin A) or particulate (bacteria) stimulation. Microbicidal activity against Pseudomonas aeruginosa, Listeria monocytogenes, and Candida albicans was also determined for each cell type. Finally, the capacity of rIFN gamma treatment (200 U/ml for 24 h) to enhance these cellular activities was determined. Oxidative activity of AM was greater than that of blood monocytes (p less than 0.01, bacteria; p less than 0.02, Con A). Likewise, AM exhibited greater killing of P. aeruginosa (p less than 0.01) and L. monocytogenes (p less than 0.01) than did monocytes. Neither cell killed C. albicans. Treatment with rIFN gamma greatly enhanced both respiratory burst and microbicidal activity of blood monocytes, but had no effect on AM respiratory burst. Despite this, rIFN gamma-treated AM did exhibit some enhanced killing of L. monocytogenes (p less than 0.05). We conclude that oxidative microbicidal activity of resident AM greatly exceeds that of blood monocytes, but that blood monocytes are relatively more susceptible to activation by rIFN gamma.

Adult↗

Relation of cytosolic calcium to the microbicidal activation of blood monocytes by recombinant gamma interferon.

Oxygen metabolism and calcium ion (Ca++) handling in blood monocytes were greatly affected by treatment with recombinant gamma interferon (rIFN-gamma). Incubating the monocytes with rIFN-gamma resulted in increased basal production of superoxide anion, as well as a significantly enhanced respiratory burst in response to concanavalin A (Con A). A concomitant increase in microbicidal activity against Listeria monocytogenes was observed, and cell membrane permeability to Ca++ was enhanced by treatment with rIFN-gamma. Con A stimulation was also associated with acute rises in cytosolic-free calcium, and these calcium transients were greatly augmented in cells pretreated with rIFN-gamma. The enhanced respiratory burst and the increased calcium transients were completely neutralized by a monoclonal antibody to rIFN-gamma. Furthermore, enhancement of the respiratory burst and calcium transients occurred in a parallel dose-response range for rIFN-gamma. Blocking the intracellular release of calcium into cytosol by TMB-8 abrogated the capacity of rIFN-gamma to enhance the monocyte respiratory burst. Thus, not only was rIFN-gamma treatment of monocytes associated with altered calcium metabolism, but calcium from intracellular pools was essential to the expression of this activated state during Con A stimulation.

Blood Bactericidal Activity↗

Comparative evaluation of ciprofloxacin, enoxacin, and ofloxacin in experimental Pseudomonas aeruginosa pneumonia.

The therapeutic activity of ciprofloxacin, enoxacin, and ofloxacin was evaluated in guinea pigs with acute and chronic experimental Pseudomonas aeruginosa pneumonia. Intratracheal instillations of P. aeruginosa resulted in fatal pneumonia in all untreated animals within 36 h. Among treatment groups (80 mg/kg [body weight] per day), cumulative survival rates were: 47%, ciprofloxacin; 55%, enoxacin; and 42%, ofloxacin. These rates were not significantly different. Intrapulmonary killing of P. aeruginosa was equivalent 3 h after a single dose of ciprofloxacin or ofloxacin (20 mg/kg) or enoxacin (40 mg/kg). The combination of ciprofloxacin with azlocillin, ceftazidime, or tobramycin did not increase the efficacy of intrapulmonary killing of P. aeruginosa over that of ciprofloxacin alone. A chronic, nonfatal bronchopneumonia was induced in guinea pigs by intratracheal instillation of microscopic agar beads impregnated with a mucoid strain of P. aeruginosa. Compared with no treatment, ciprofloxacin and enoxacin produced greater than or equal to 99.9% intrapulmonary killing, and ofloxacin sterilized the lungs completely, after 4 days of treatment. In no quinolone-treated animal did resistant strains of P. aeruginosa emerge during 4-day treatment periods. In further studies with the chronic model, oral and parenteral ciprofloxacin treatment were found to be equivalent in efficacy. We conclude that several quinolone derivatives may be effective for the treatment of P. aeruginosa pneumonia and that combinations of quinolones with beta-lactams or aminoglycosides may not increase efficacy against P. aeruginosa pneumonia.

Animals↗

Verapamil impairs human neutrophil chemotaxis by a non-calcium-mediated mechanism.

The in vitro effect of pharmacologic concentrations (10(-8) to 10(-6) mol/L) of verapamil on human neutrophil migration and response to chemotactic signals was examined. Human neutrophils were preincubated (15 minutes) in verapamil and then assayed for chemotactic response to formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe) (10(-8) mol/L). Cell viability was not affected by verapamil treatment. Verapamil-treated cells displayed 40% to 50% reductions in directed migration at all concentrations (P less than 0.02). Activated random migration (chemokinesis) was also impaired by verapamil treatment, but random locomotion was not affected except at a high concentration (10(-6) mol/L). This pharmacologic action of verapamil was not rapidly reversible by washing cells free of drug, but it was necessary that cells be exposed to drug before the chemotactic signal. In addition to f-Met-Leu-Phe, chemotactic response to activated human serum was also reduced for neutrophils. Several experiments were conducted to determine whether verapamil affected neutrophils as a calcium antagonist. Calcium antagonist binding-site assays using radiolabeled dihydropyridines provided no evidence for the presence of calcium channels in neutrophil membranes. Also, 45Ca2+ uptake assays demonstrated increased uptake of 45Ca2+ by f-Met-Leu-Phe-stimulated neutrophils, but no effect on uptake by verapamil exposures (10(-6) mol/L). Finally, the cytosolic calcium-chelating dye, quin 2 acetomethoxy ester (quin 2), was used as a fluorescent indicator to measure cytosolic Ca2+ concentrations, [Ca2+]i, in neutrophils. Verapamil exposures over a wide concentration range (10(-6) to 10(-4) mol/L) did not affect resting [Ca2+]i or [Ca2+]i transients after f-Met-Leu-Phe (10(-8) mol/L) stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

[Diagnosis and antibiotic treatment of infectious diseases in general practice. Results of an inquiry].

In February 1982 a questionnaire was sent to 2138 doctors in general practice in West Berlin, to obtain data relating to the incidence and treatment of infectious diseases. Replies were received from 453 (21%). Regular bacteriological tests were undertaken only for urinary tract infections, by 60% of those replying. The 453 doctors reported a total of 9280 cases of infectious disease during a one-week period, 6094 respiratory and 1723 urinary ones. Antibiotic prescriptions numbered 6118 during this period, 56.7% for respiratory and 27% for urinary tract infections. Indications for antibiotic treatment were predominantly decided on clinical grounds.

Anti-Bacterial Agents↗

Pharmacokinetics of multiple doses of ceftizoxime and their influence on fecal flora.

The pharmacokinetics of ceftizoxime, a new beta-lactam antibiotic, were studied in eight normal volunteers after single and multiple i.v. doses of 2 X 2 g daily for eight days. The mean maximum serum concentration after the first 20 min of infusion on the first day was 176.9 +/- 32.9 micrograms/ml decreasing to 11.0 +/- 4.1 micrograms/ml after 4 h and to 0.67 +/- 0.2 micrograms/ml after 12 h. Mean 12 h urine recovery was 78.8 +/- 9.0%. The half-life of ceftizoxime was 136 +/- 36 min. Volume of distribution was 22.9 +/- 8.1 1/100 kg body weight, AUCtot 208 +/- 33 micrograms/ml x h, total body clearance 151 +/- 33 ml/min, and renal clearance 110 +/- 23 ml/min. No ceftizoxime accumulation was registered during the administration period. Computed multiple-dose values were in good agreement with the measured values, and the pharmacokinetic parameters on the first, fourth and eighth days showed no significant differences. During the study period, the fecal flora displayed a reduction of sensitive gram-negative aerobic bacteria, a slight increase in the amount of enterococci (10(6) to 10(8)/g feces), and no change in the number of Bacteroides fragilis. Some resistant gram-negative strains increased during the administration period, but most of them could no longer be detected two weeks after administration. Tolerance of ceftizoxime was good in four volunteers. Four other volunteers had gastro-intestinal symptoms and mild fever reactions. One female volunteer was assumed to have an allergic drug reaction. Biochemical, hematological, virological and serological data showed no abnormalities in seven volunteers.

Adult↗

Biliary excretion and pharmacokinetics of cefoperazone in humans.

Six patients, 40 to 81 years of age, requiring T-tube drainage of their common bile duct, were studied to assess the biliary tract excretion and pharmacokinetics of cefoperazone. Each patient received 2.0 g of cefoperazone iv over 15 min. Cefoperazone concentrations were determined in serum, urine and bile by means of bioassay and HPLC. The results were compared with a pharmacokinetic study in healthy volunteers. The mean total recovery rate of cefoperazone in urine and bile was with bioassay: 64.5 +/- 15.3% (HPLC: 62.4 +/- 15.5%) in 24 h. 18.6 +/- 14.0% (11.5 +/- 7.1%) were found in the bile and 45.9 +/- 16.2% (50.9 +/- 19.7%) in urine. Peak bile concentrations were 3642 +/- 2975 mg/l (2259 +/- 1337 mg/l) after 2-3 h. The serum levels of cefoperazone showed a slow decrease in patients with a long terminal half life (T1/2 gamma) of 380 min from 295 +/- 90 mg/l initially to 15.9 +/- 11.3 mg/l after 12 h. In normal subjects, serum concentrations decreased much faster (T1/2 gamma = 143.5 +/- 20.0 min) from 232.8 +/- 28.6 mg/l to 1.16 +/- 0.73 mg/l after 12 h. Recovery in urine was 21.4 +/- 5.6%. Using HPLC analysis, we found cefoperazone A in small concentrations in the serum and in higher concentrations in the bile and urine of the operated patients. It is debatable whether cefoperazone A is a true metabolite in vivo or a physical degradation product.

Adult↗