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Fluoroquinolones are known to penetrate well into the infectious foci such as lung mucosa, epithelial lining fluid and alveolar macrophages achieving higher target site concentrations than the corresponding serum levels. In order to integrate the in vitro antibacterial activity and pharmacokinetics of moxifloxacin and levofloxacin, their bactericidal efficacy was assessed by simulating human serum and lung tissue concentrations using Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae as indicator organisms. The bacteria were exposed to fluctuating moxifloxacin and levofloxacin concentrations simulating the drug levels in serum, lung mucosa, epithelial lining fluid and alveolar macrophages. The following parameters were deduced from the kill curves: area under the bactericidal kill curve normalized to the initial inoculum (AUBKC norm), the time needed to reduce the inoculum by 3 log(10) titers, and the initial bactericidal activity. In general, all these three parameters were for all the bacterial isolates having been exposed to moxifloxacin concentration dependent. In contrast, beyond a levofloxacin concentration of optimal bactericidal effect, higher drug concentrations did not further augment the bactericidal activity of levofloxacin. These data demonstrate that not all fluoroquinolones share the same pharmacodynamic targets needed to maximize their antibacterial effect.

Antibiotic activity against common respiratory pathogens can be affected by the pH of the medium (in vitro) or the bodily fluid (in vivo) in which bacteria are present. The ionized fraction of an antibiotic is not able to efficiently penetrate bacterial or mammalian membranes, reducing the quantity of molecules able to exert their antibacterial effect resulting in elevated MIC values This study shows that the activity of macrolide antibiotics is particularly sensitive to acidic conditions, whereas a ketolide and fluoroquinolones are much less affected. Furthermore, induction of spontaneous and multistep macrolide resistance is greatly increased in acidic medium. In contrast, telithromycin and moxifloxacin did not induce resistance at any pH. Antibiotics which are less likely to induce resistance in vitro may also be less likely to induce the development of resistance in patients with respiratory tract infections.

Background: The aim of this study was to establish whether Chlamydia pneumoniae is implicated in the development of restenosis in patients with coronary heart disease (CHD) after percutaneous transluminal coronary angioplasty (PTCA)., Patients and Methods: 67 patients were selected for study after they underwent control angiography after PTCA. Sera were tested for anti-chlamydial antibodies with a genus specific ELISA and a species-specific microimmunofluorescence test (MIFT). Oropharyngeal specimens were examined for the presence of antigen with a Chlamydia immunofluorescence test (IFT), C. pneumoniae IFT and semi-nested PCR. In addition, anamnestic findings were also included. To determine the general level of antibodies, an age- and sex matched control group of 180 persons was also examined for Chlamydia and C. pneumoniae serology., Results: Coronary angiography revealed that 31 of the 67 patients had developed a restenosis. There was no significant correlation between serological and angiographic findings. However, the MIFT showed a higher positive rate, especially in IgA, in the restenosis group. C. pneumoniae was detected in the oropharynx by PCR and/or IFT in 20.8% and 16.0% of the cases in patients with and without a restenosis. PCR found more C. pneumoniae-positive cases in the restenosis patients than IFT. No association was found between the detection of Chlamydia antigen and serology. The women with restenosis were more frequently smokers (p = 0.012). Men with restenosis were significantly older (p = 0.015). C. pneumoniae serology based on the rELISA or the MIFT did not show any correlation with restenosis., Conclusion: No evidence was found to suggest that positive C. pneumoniae serology is a risk factor for the development of restenosis. However, whether the species-specific serological test, especially for IgA-antibodies, and the detection of C. pneumoniae in oropharyngeal specimens by PCR might be reliable diagnostic markers in these cases remains to be determined.

Background: The cagA (cytotoxin-associated gene A) protein is found in about 50% of Helicobacter pylori strains; its clinical relevance in gastroduodenal disease is uncertain., Patients and Methods: The frequency of IgG antibodies to cagA was studied by using a commercial Western blot assay in sera of 189 patients with endoscopically and histologically confirmed gastroduodenal disease. In addition, 38 H. pylori strains isolated from biopsies were analyzed by immunofluorescence test (IFT) and PCR for detection of cagA protein and cagA gene sequences, respectively., Results: 54.3-60.0% of all patients with gastrointestinal diseases (chronic gastritis, gastric or duodenal ulcer and chronic duodenitis) and 28.6% with a normal mucosa were found to be positive for anti-cagA IgG antibodies. There was no significant difference in anti-cagA IgG seroprevalence between the different clinical entities. CagA-positive (cagA+) H. pylori strains were detected in 44.7% and 50% of the 38 isolates by PCR and IFT, respectively. 22 of 23 patients infected with cagA+ strains had anti-cagA antibodies. Using PCR as a gold standard, the sensitivity and specificity of the cagA IgG Western blot were 100.0% and 35.0%, respectively; the sensitivity and specificity of the cagA IFT were 76.5% and 71.4%, respectively. The incidence of the cagA+ H. pylori strains detected either by PCR or IFT was significantly higher (p < 0.05 and p < 0.01, respectiveLy) in patients with chronic duodenitis, gastric or duodenal ulcer compared to patients with chronic gastritis (66.7%, 80% and 30.4%, respectiveLy)., Conclusion: In this study the cagA-specific serological status in H. pylori infections as diagnosed by IgG Western blot was of no predictive value for severity of disease. In contrast, the cagA status of H. pylori isolates, diagnosed by IFT or PCR, was a predictive marker for severe disease and, therefore, also of clinical relevance in the assessment of the virulence of the infecting strain.

Ten patients about to undergo a colorectal operation lasting an average of three hours received 500 mg each of imipenem and cilastatin i.v. preoperatively. During the operation blood and tissue samples were taken in order to determine the serum kinetics of the substances as well as the levels of imipenem in the cutis, subcutis, fascia, muscle, parietal peritoneum and colon. The imipenem concentrations were measured by HPLC. The mean peak serum concentration was 26 mg/l, the mean half-life 55 min and the AUC 40 mg/l/h-1. The serum pharmacokinetics of imipenem was subject to substantially larger fluctuations in this patient group than in subjects or patients without surgery. Imipenem rapidly penetrates into tissue, with peak concentrations being reached after 10-25 min. The highest imipenem concentrations were found in the colon, the lowest in the cutis and subcutis. After 1 h a level of 8 mg/kg imipenem was still found in the colon. The concentrations were greater than 1 mg/kg in all tissues for more than 3 h p. a. and thus within this period exceeded the MICs of Escherichia coli and Bacteroides fragilis, the indicator organisms of intraabdominal infections.

153 strains of Klebsiella pneumoniae from 16 microbiological institutes in Germany, Austria and Switzerland were typed biochemically and serologically; their sensitivities to cefoxitin, cefotaxime, ceftazidime, ceftriaxone, lamoxactam, thienamycin and gentamicin were determined. The strains could be classified into seven biotypes and 43 K-antigen types. The distribution of the K-antigen types was random, and spread over the whole spectrum of the 72 possibilities. Regional variations were not observed. 4.6% of the isolates were resistant to cefoxitin and 23% were moderately sensitive. 98% of these Klebsiella strains were sensitive to the new cephalosporins which were also effective against gentamicin-resistant isolates accounting for 12% of all isolates studied. Cefoxitin was only slightly active against such strains. The effect of a standard concentration of each agent on bacterial cultures during their growth phase was measured in the Jouan biophotometer. The beta-lactamase-stable cephalosporins had a permanent bactericidal effect on the enzyme-producing reference strain, although the latent period varied considerably in some cases. Piperacillin and cefoperazone were not bactericidal in this test.

The first non-metallic oxygen carrier, tetrachlorodecaoxide (TCDO), showed in vitro antibacterial activity among aerobic and anaerobic bacteria. The lethal dose for Escherichia coli, for example, was 150 micrograms/ml whereas 15 micrograms/ml reduced the bacterial amount after a latent period of two hours, but regrowth started after four hours. The bactericidal effect of TCDO, however, was dose-dependent and species-specific. This suggests that some aerobic bacterial species might not be able to produce sufficient amounts of protecting enzymes like catalase or superoxide dismutase. The computer controlled measurement of chemiluminescence was used as a model for the phagocytic activity. With isolated human granulocytes and opsonized zymosan as antigen no increase in peak counts per minute was observed compared with controls without TCDO. However, with human whole blood, positive effects were seen using TCDO together with zymosan as well as specific and non-specific opsonized Klebsiella pneumoniae K 17. It seems that whole blood possesses additional, but as yet unknown biocatalysers to split TCDO into oxygen and chloride.

The subspecies intestinalis and fetus of Campylobacter fetus are opportunistic pathogens in humans. So far, some 200 types of disease due to these pathogens have been reported from all over the world, and six new diseases are briefly described in this paper. The most frequent disease is sepsis, followed by meningitis. While ticarcillin, erythromycin, clindamycin and tetracycline are the antibiotics which show activity against these species, a large degree of resistance is seen against cephalothin, cefazolin, cefuroxime, cefoxitin and cefotaxime. There is a moderate degree of sensitivity to gentamicin. The epidemiology of the disease is not clear, and about twice as many men are affected as women. Subspecies intestinalis was isolated in 95% of all diseases. Antibodies to Campylobacter fetus were detected in 3.9% of the population.

After oral administration of 500 mg cefaclor, antibacterially active metabolites could not be detected in human urine using thin layer chromatography followed by bioautography. Degradation products of cefaclor could also not be detected in the serum of human volunteers (n = 10) using high pressure liquid chromatography with a reversed phase system. Cefaclor was eluated as a single and homogenous peak with a retention period of 2.9 min. High pressure liquid chromatography for the measurement of cefaclor serum levels and a technique for preparation of serum samples are described. After administration of 500 mg cefaclor to volunteers (n = 10), the average peak serum concentration of 9.8 mg/l, determined by high pressure liquid chromatography, was observed after one hour. Four hours later the serum level was 0.3 mg/l. Using microbiological methods no statistically significant difference was obtained in comparison with the chromatography results. Some of the sera stored at -75 degrees C for four weeks showed a substantial loss of activity of cefaclor.

The influence of Ly146032, a new acidic lipopeptide, on chemotaxis, luminol-dependent chemiluminescence of human polymorphonuclear leukocytes (PMN) and phythemagglutinin induced lymphocyte transformation of murine cells was investigated. At therapeutic range there was no remarkable effect on the parameters tested. Incubation with more than 20 mg/l Ly146032 was followed by depression of chemiluminescence, whilst transformation of maximally PHA stimulated lymphocytes was suppressed by more than 32 mg/l Ly146032.

Four-hourly urine from volunteers and patients who had received penicillins orally or intravenously was investigated by means of thin layer chromatography and bioautography. Antibacterially active metabolites were not detected with only two of 12 penicillins, namely amoxicillin and mezlocillin. In the case of the other penicillins the metabolites possessed variable antibacterial activity as could be demonstrated using different test microorganisms. After administration of carbenicillin esters three antibacterially active spots were detected, one of which corresponded to penicillin G; the other two were active against Pseudomonas aeruginosa. The bioautogram after treatment with azlocillin showed two components which were active against Bacillus subtilis, Staphylococcus aureus and Escherichia coli; only the rapid moving component was active against P. aeruginosa, however. The formation and chemical nature of these additional active components is still to a large extent not understood. It is quite possible, however, that they affect the bio-availability of an antibiotic.

The isotype-specific antibody response to influenza vaccination in 36 patients undergoing chronic intermittent hemodialysis was analyzed by an influenza subtype-specific immunofluorescence test. The immune response was recorded at regular intervals over five months. On the basis of fourfold IgG titer rises as the classical parameter protection from infection was assumed to occur in more than 85% of healthy adults to each of the influenza antigens. In contrast, about 70% of the patients on hemodialysis had responded to influenza A H1N1 and H3N2 vaccines while only 50% of the patients on hemodialysis had responded to influenza B antigen. However, patients showed decreased rates and lower peak responses in IgA, IgM and IgG antibodies to influenza A and B antigens. Probably as a result of the underlying renal disease the different kinetics of antibody responses and the lower influenza specific immunoglobulin levels resulted in lower seroconversion rates in hemodialysis patients compared to those in healthy volunteers.

Eighteen patients scheduled for surgical lens removal were assigned to six groups of three patients each. These patients received 25 mg/kg lamoxactam i. v. 30 to 180 min prior to surgery. In the course of the operation, aqueous humor was obtained and a serum sample taken to determine the antibiotic concentration. The mean peak serum level was 154.5 mg/l after 30 min; it was still 46.4 mg/l after 3 h. The lamoxactam concentrations in the aqueous humor increased slowly. Peak levels after 2 h were 4.2 mg/l. The ratio of aqueous humor level: serum level after 1 h was 4.7%, after 1.5 h 5.3% and after 2 h 6.9%. The ratio then remained constant up to the third hour. Aside from some gram-positive bacterial species and Pseudomonas species, all relevant microorganisms which cause eye infections are included in lamoxactam's spectrum of susceptibility.

There is a correlation between tissue oxygen tension, incidence of infection and disturbance of wound healing. Scientific investigations in recent years have documented that infection and tissue repair are processes consuming oxygen. Animal experiments have shown that oxygenation of the tissue is essential for the elimination of pathogens, the stimulation of phagocytosis as well as for the degradation of dead tissue structures and the synthesis of new tissue structures. Hypoxia and hypovolemia are of crucial significance for the impairment of organ functions. An effective therapy for disorders of oxygenation has not been feasible so far, except for clinical anesthesiological efforts to increase the oxygen saturation of hemoglobin and hyperbaric oxygen therapy. However, it has recently been possible to synthesize an oxygen carrier which supports respiratory oxygen physiologically. With tetrachlorodecaoxide (TCDO), a causal therapeutic concept for the topical treatment of infected hypoxic wounds with chronic disturbance of wound healing has been introduced for the first time.

The sources of error in the measurement of bacterial growth curves in closed systems are demonstrated by opacity. In investigations of bactericidal kinetics, it is necessary to observe the viable count by optical density because of the lesser susceptibility. Results obtained in this way cannot simply be applied to the chemotherapy of bacterial infections. Some of the findings may be important in view of our knowledge about the mechanism of antibacterial action, e. g. the latent period is important and indicates the speed of bactericidal action. In our experiments with eight cephalosporins and Klebsiella pneumoniae, the latent periods varied from 19.8 min for cefazolin to 102.8 min for cefuroxime. The inoculum dependence of antibacterial activity which was discovered in these investigations is also significant for determining an optimal dose because the bacteria should be reduced to a minimum by an initial high dose of antibiotic.

During an outbreak of infections with multiple-resistant Staphylococcus aureus, 22 strains were isolated from 12 patients between November 1983 and March 1984 on two surgical intensive care units at Kiel University Hospital. Susceptibility of all strains was tested with the disc diffusion method and a microdilution test using different inocula of 10(2) and 10(5) cfu/ml. All strains were resistant to beta-lactam antibiotics, including thienamycin as well as to gentamicin, clindamycin, doxycycline, erythromycin and fosfomycin. Rifampicin was the most active substance in terms of w/v, followed by fusidic acid, ciprofloxacin, vancomycin, and trimethoprim/sulfamethoxazole. Netilmicin and chloramphenicol showed only moderate activity in relation to the antibiotic breakpoint, but were considered sensitive according to the disc diffusion test. Caution should be reserved for the use of imipenem against multiply-resistant staphylococci.

The beta-lactamase activity of 510 recently isolated Enterobacteriaceae was investigated with a quantitative photometric test. Beta-lactamase could be detected in 55 percent of the Enterobacteriaceae. At the same time minimal inhibition concentration (MIC) of beta-lactam antibiotics was determined. There was no correlation between MIC values and lactamase activity. For correct antibacterial therapy the clinician requires information on the lactamase activity of isolated bacteria in addition to the antibiogram. The qualitative test is useful for screening.

The first non-metallic oxygen carrier, tetrachlorodecaoxide (TCDO), showed in vitro antibacterial activity among aerobic and anaerobic bacteria. The lethal dose for Escherichia coli, for example, was 150 micrograms/ml whereas 15 micrograms/ml reduced the bacterial amount after a latent period of two hours, but regrowth started after four hours. The bactericidal effect of TCDO, however, was dose-dependent and species-specific. This suggests that some aerobic bacterial species might not be able to produce sufficient amounts of protecting enzymes like catalase or superoxide dismutase. The computer controlled measurement of chemiluminescence was used as a model for the phagocytic activity. With isolated human granulocytes and opsonized zymosan as antigen no increase in peak counts per minute was observed compared with controls without TCDO. However, with human whole blood, positive effects were seen using TCDO together with zymosan as well as specific and non-specific opsonized Klebsiella pneumoniae K 17. It seems that whole blood possesses additional, but as yet unknown biocatalysers to split TCDO into oxygen and chloride.