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Biomedical subjects

R Auckenthaler

Publications and source records attributed to R Auckenthaler.

At least 91 records · Page 5Linked to original sources

Comparative evaluation of the BCB Roche and Oxoid Signal blood culture systems.

The agar-slide blood culture system BCB Roche was compared with the Oxoid Signal blood culture system using 2,266 paired blood cultures. A total of 271 (12%) paired sets were culture-positive, including 222 (9.8%) yielding pathogens associated with septicemia and 50 (2.2%) yielding likely contaminants. In the recovery of the total 235 isolates considered as pathogens, the BCB Roche system yielded 202 (85.9%), the Oxoid Signal 211 (89.8%); 178 (75.7%) were cultured by both systems. There was no statistically significant difference between the two systems in their sensitivity, contamination-rate and detection time, except for gram-positive organisms, which were detected earlier by the Oxoid Signal system. Both systems performed well and were easy to handle.

Agar↗

Serum levels of ciprofloxacin after single oral doses in patients with septicemia.

Ciprofloxacin serum levels were measured after administration of the drug to 36 patients with septicemia (at least one positive blood culture) who were able to take oral medication. Patients were randomly allocated to receive ciprofloxacin 500 mg p.o. (n = 21) or 200 mg i.v. over 30 min (n = 15). A first dose was administered 18-30 h after the last positive blood culture (day 1), and a second dose four days later (day 5) in some patients. In addition to ciprofloxacin, standard antibiotics were administered. Organisms isolated were Escherichia coli (15), other gram-negative bacteria (6), Streptococcus pneumoniae (7), Staphylococcus aureus (2), and other gram-positive bacteria (6). None of the patients vomited. Ciprofloxacin serum concentrations 1 h after oral administration were in the range 0.09-2.32 mg/l, and 2 h after administration in the range 0.5-7.27 mg/l. The average terminal half-life was 8.6 h. In individual patients serum concentrations and area-under-the-curve values were compared. Poor correlation was found between values measured on day 1 and day 5 after oral administration, whereas the correlation was excellent after i.v. administration. Serum levels 2 h after oral administration were 30-900 times the MICs for the gram-negative organisms, but were in the range of the MICs for the gram-positive organisms in some cases. In conclusion, ciprofloxacin serum levels are difficult to predict in septicemia patients after oral administration, but probably suffice to treat infections caused by gram-negative organisms.

Administration, Oral↗

Synergistic effect of quinolones and oxacillin on methicillin-resistant Staphylococcus species.

Various combinations of antistaphylococcal antimicrobial agents have been tested against 17 selected Staphylococcus isolates, including methicillin-susceptible and methicillin-resistant strains of S. aureus and coagulase-negative Staphylococcus species. With the checkerboard technique the following combinations were tested: oxacillin-ofloxacin, oxacillin-temafloxacin, oxacillin-fleroxacin, vancomycin-fleroxacin, gentamicin-fleroxacin, and rifampin-fleroxacin. Against methicillin-resistant staphylococci the combination oxacillin-quinolone tested at 35 degrees C always showed a fractional inhibitory concentration (FIC) index of less than 0.75, which is interpreted as synergistic or additive. Equal or more synergistic effects were observed at 30 degrees C. In contrast, when methicillin-susceptible Staphylococcus species were tested, the FIC for the combination oxacillin-quinolone was always 1 or 2, which is considered to be indifferent. For the other mentioned combinations the FICs were also 1 or 2. Killing kinetics showed synergistic or additive bactericidal activity for the combination oxacillin-ofloxacin against methicillin-resistant Staphylococcus species, killing 1.5 to 2.8 log10 CFU more of these per ml than did the most active drug after 24 h of incubation. This difference was not observed for methicillin-susceptible strains. In vitro evidence for the potential clinical use of quinolones in treating infections due to methicillin-resistant staphylococci in combination with a beta-lactamase-resistant penicillin is provided.

4-Quinolones↗

Permeability and penicillin-binding protein alterations in Salmonella muenchen: stepwise resistance acquired during beta-lactam therapy.

A patient with Salmonella muenchen sepsis was unsuccessfully treated with ampicillin. During therapy, four strains that showed stepwise ampicillin resistance and affected other beta-lactams and unrelated antibiotics were isolated sequentially. Resistance was caused by decreased outer membrane permeability associated with diminished expression of porin OmpF. Furthermore, the most resistant isolate overproduced the PBP 3 target molecule.

Anti-Bacterial Agents↗

Quantitative cultures of biopsy specimens from cutaneous cellulitis.

To study the microbiologic features of cutaneous cellulitis prospectively, quantitative biopsy cultures were carried out in 25 patients who were hospitalized for an untreated cutaneous cellulitis. Biopsy specimens were obtained from both the center and the advancing edge of erythema. Only nine biopsy specimens (three central and six peripheral) (18%) of 50 yielded pathogens. Needle aspiration cultures were performed in seven cases: two yielded pathogens (28.5%). The density of microorganisms was low, ranging from less than 80 colony-forming units (CFUs) per gram of tissue to 1360 CFUs/g of tissue, except next to the edge of an ulcer (two cases), where densities reached 3.2 x 10(6) CFUs/g of tissue. Cutaneous cellulitis shows a discrepancy between the low density of microorganisms and the intensity of the inflammation. A factor other than infection must be implicated. This might be lymphatic failure, which is found in 72% of patients.

Bacteriological Techniques↗

[Infectious pneumopathies in immunodepressed patients. Value of the study of bronchoalveolar lavage fluid].

During a period of 16 months 26 fluid specimens obtained by broncho-alveolar lavage (BAL) in 24 immunocompromised patients were examined. This material included 13 HIV positive patients and 11 patients presenting malignant hemopathies (MH), of whom 7 had had a blood marrow transplantation. The BAL fluid was divided into two equal parts, one of which was sent to the Institute of Pathology and the other to the Laboratory of Bacteriology of Geneva University Hospital. In some cases a transbronchial biopsy was also studied. Eight out of 13 HIV positive patients presented a Pneumocystis carinii infection and one a cytomegalovirus (CMV) infection (associated with atypical mycobacteria infection). In another case streptococcal pneumonia was observed. In 3 patients, analysis of the BAL fluid failed to yield a diagnosis. In the 11 patients with MH, 2 cases of CMV, 2 infections with Candida albicans and one with Aspergillus fumigatus were found. In 2 patients the pneumopathy was due to bacterial infection. Four BAL fluids failed to yield a diagnosis; however, in one of these transbronchial biopsy revealed interstitial pneumonia of unknown origin. On the basis of our material and comparison with clinica, radiological and serological data, it appears that BAL fluid analysis is a helpful and rapid diagnostic aid in infectious pneumopathies of immunocompromised patients. This is especially true of AIDS patients in whom the most common pulmonary complication is Pneumocystis carinii pneumonia. However, success of the analysis requires close cooperation between clinician, bacteriologist and pathologist.

Acquired Immunodeficiency Syndrome↗

Serological study of meningococcal isolates in Switzerland and France 1980-1986.

A study was performed of 342 disease-related strains of meningococci isolated in Switzerland and France between 1980 and 1986, including more than 50% of all strains isolated in Switzerland in 1986. Using a newly developed spot-blot enzyme-linked immunoassay and a panel of monoclonal anti-meningococcal antibodies, 96% of all strains were shown to react with at least one antibody. In both countries more than 50% of the strains were group B. In France serotype 2a was the prevalent serotype and was often associated with subtype P1.2. In Switzerland serological markers of epidemic strains recently described in Northern Europe (serotype 15 and subtype P1.16) were observed with increasing frequency in 1986. However, serotype 4 has been prevalent in Switzerland since 1980 and no clonal population was seen to emerge.

Antibodies, Monoclonal↗

Fibronectin, fibrinogen, and laminin act as mediators of adherence of clinical staphylococcal isolates to foreign material.

Bacterial adherence to polymer surfaces is a required early step in intravenous (iv) device infection. We collected eight strains of Staphylococcus aureus and 19 of coagulase-negative staphylococci from patients with proven iv device bacteremia and studied the role of plasma or connective-tissue proteins in promoting bacterial adherence to polymethylmethacrylate (PMMA) coverslips. Although only a negligible percentage of organisms adhered to albumin-coated PMMA, surface-bound fibronectin significantly promoted adherence of all isolates. Fibrinogen markedly promoted adherence of all S. aureus strains but of only four coagulase-negative strains. Thus, coagulase-negative staphylococci revealed a marked heterogeneity in adherence to fibrinogen-coated surfaces, a result suggesting the existence of heretofore unknown receptors for fibrinogen. Laminin promoted adherence of staphylococci to a much lower extent. Although strain specific, adherence of clinical staphylococcal isolates to foreign surfaces is significantly increased by fibronectin, fibrinogen, and laminin, an observation suggesting the possible contribution of these proteins to the pathogenesis of iv device infection.

Bacterial Adhesion↗

Effect of a single dose of cefotaxime or ceftriaxone on human faecal flora. A double-blind study.

The effect of cefotaxime and ceftriaxone on faecal flora was investigated in women undergoing routine vaginal or abdominal hysterectomy. Three groups of 9 patients received, in a double-blind fashion and just before surgery, cefotaxime 2g intravenously, ceftriaxone 2g intravenously or no antibiotic (controls). Stools were collected before prophylaxis (sample 1) and after surgery (samples 2 and 3). The only alteration after cefotaxime was a decrease of non-fastidious aerobic Gram-negative flora in sample 2. The same effect was more pronounced after ceftriaxone (p less than 0.01) which, in addition, increased yeast colonies (p less than 0.05) in sample 2. In sample 3, more resistant (MIC greater than 32 mg/L) aerobic and anaerobic bacteria were found after ceftriaxone (log10 median 7.5 and 9.0, respectively) than after cefotaxime (4.2 and 6.0) or in controls (4.4 and 6.6) [p less than 0.01 in each case]. Group D streptococci and Gram-positive cocci remained unchanged in the 3 groups. Clostridium difficile cytotoxin assays were negative. The effects on faecal flora were more pronounced after ceftriaxone.

Bacteria, Aerobic↗

[Histological study of a case of chondrocostal aspergillosis].

Histological study of biopsy specimens successively taken from the 7th, 5th and 6th right chondrocostal regions in a 33 year-old man; the patient was under chemotherapy for a diffuse lymphoma and has been operated for an aspergilloma of the right lung superior lobe. Non-specific chronic osteomyelitis was observed as well as Aspergillus fumigatus perichondritis (acute and chronic) which had lead to cartilage fragmentation. Cartilage fragmentation could be attributed to an enzymatic chondrolysis induced by polymorphonuclears inflammation. Such matrix degradation seems to favour the penetration of aspergillus into the cartilage surface. This case report recalls that fungi (including Aspergillus despite it appears exceptional) must be considered as a possible cause of osteomyelitis, particularly in immunosuppressed patients.

Adult↗

[Osteomyelitis].

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Anti-Bacterial Agents↗

Comparison of immunological methods for diagnosis of pneumococcal pneumonia in biological fluids.

Five immunological tests were evaluated for their ability to detect Streptococcus pneumoniae antigen in serum and urine simultaneously as a means of rapid diagnosis in 40 patients with bacteremic or non-bacteremic pneumococcal pneumonia or pneumonia with other etiologies. Serum and urine were screened in parallel with counterimmunoelectrophoresis (CIE), two commercial latex agglutination kits - the Slidex pneumokit (LA-SPK) and the Bactigen Streptococcus pneumoniae kit (LA-Bac) - the coagglutination Phadebact Pneumococcus test (CoA) and a newly developed enzyme-linked immunosorbent assay (ELISA) containing the immunoglobulin G fraction from rabbit pneumococcal antiserum. The detection rate for accumulated serum in bacteremic patients was 18% for LA-Bac, 24% for CIE, 47% for LA-SPK and CoA and 76% for ELISA, whereas antigenuria was present in only 29% for LA-SPK, 24% for CIE, 19% for CoA, 14% for LA-Bac and 5% for ELISA. Detection by ELISA of pneumococcal antigen in severely ill patients can predict bacteremia and rapidly confirm the diagnosis of pneumococcal pneumonia if sputum and results of blood cultures are not available.

Agglutination Tests↗

Early termination of a prospective, randomized trial comparing teicoplanin and flucloxacillin for treating severe staphylococcal infections.

In a prospective, randomized trial, teicoplanin (at a 400-mg intravenous loading dose followed by 200 mg/day intravenously or intramuscularly) was compared with flucloxacillin (8 g/day) in patients with severe staphylococcal infections. Teicoplanin proved unsatisfactory for the following reasons: failures or relapses were more frequent in the teicoplanin group, and blood levels were difficult to predict and tended to be low 24 hr after the loading dose. Future trials with this agent should use much-higher doses.

Adult↗

In-vitro activity of roxithromycin against respiratory and skin pathogens.

The activity of roxithromycin was determined by a microdilution method, in comparison with erythromycin, spiramycin and josamycin. Roxithromycin and erythromycin showed very similar MICs against staphylococci, Streptococcus pneumoniae, Str. pyogenes and Haemophilus influenzae. In most cases, spiramycin and josamycin appeared similarly or more active. The activity of roxithromycin against Mycoplasma pneumoniae, Legionella spp., Chlamydia psittaci and, to some extent, against Pasteurella spp. was also assessed, by suitable in-vitro methods. Roxithromycin has a promising potential for treating selected skin and respiratory infections.

Bacteria↗

Resistance occurring after fluoroquinolone therapy of experimental Pseudomonas aeruginosa peritonitis.

Resistance emerging after fluoroquinolone therapy was investigated in a murine model of Pseudomonas aeruginosa infection. Mice were infected intraperitoneally by one of six strains and treated with pefloxacin or ciprofloxacin. In mice challenged with a low inoculum (1.6 X 10(5) CFU), no resistance occurred. With a higher inoculum (1.5 X 10(8) CFU) and after a single dose of antibiotic, posttherapy (PT1) strains with decreased susceptibility to quinolones (4- to 32-fold less) were isolated at a variable rate. The presence of talcum (125 mg) in the peritoneal cavity increased the risk of resistance after therapy. Pefloxacin (25 or 200 mg/kg) and ciprofloxacin (25 mg/kg) yielded similar resistance rates (61 to 77%), but ciprofloxacin (10 mg/kg) produced more resistance (83%) than did ciprofloxacin (50 mg/kg) (44%) (P less than 0.02). Combined with a quinolone, ceftazidime (P less than 0.001) or amikacin (P less than 0.01), but not piperacillin, reduced the emergence of resistance. After several doses of ciprofloxacin, it was found that 25-mg/kg doses every 12 h produced more resistance than did 25-mg/kg doses every 8 h or 50-mg/kg doses every 12 h. Compared with the preceding experiments using parent strains, ciprofloxacin and pefloxacin were less efficient in killing bacteria in mice infected with PT1 strains. Moreover, in one of these mice, a highly resistant PT2 strain (64-fold MIC increase for the quinolones) emerged. Besides increased MICs of the quinolones, there was a two- to eightfold increase in imipenem MIC for all PT1 and PT2 strains without alteration of other beta-lactam and aminoglycoside susceptibility. Some PT1 strains also showed a decreased susceptibility to trimethoprim and chloramphenicol. During therapy with a quinolone, resistance can emerge rapidly, especially when there is a large number of bacteria or a foreign body present. This risk may depend on the dosing schedule and may be reduced by combined therapy.

Animals↗

Combination therapy: a way to limit emergence of resistance?

The ability of antibiotic combinations to limit the emergence of resistance during therapy was evaluated in a murine model. Peritonitis was produced by injecting a mixture containing 10(8) colony-forming units of bacteria and sterilized talcum into the peritoneum. Two hours later, a single antibiotic dose was administered subcutaneously. The next day, peritoneal bacterial populations were analyzed on Szybalski's gradients. Acquired resistance was recorded when there was at least a fourfold increase in minimum inhibitory concentrations compared with untreated animals. No resistance emerged after amikacin monotherapy (15 mg/kg); however, resistance was frequently observed after monotherapy with ceftriaxone (50 mg/kg) or pefloxacin (25 mg/kg). Resistance to ceftriaxone and pefloxacin emerged, respectively, in 15 percent and 83 percent of animals with Klebsiella pneumoniae, 71 percent and 54 percent with Enterobacter cloacae, 0 percent and 83 percent with Serratia marcescens, 25 percent and 100 percent with Pseudomonas aeruginosa, and 0 percent with both Escherichia coli and Staphylococcus aureus. In mice with K. pneumoniae or E. cloacae infections, any dual combination of amikacin, pefloxacin, and ceftriaxone produced less acquired resistance than did monotherapy. In these animals, the combination of ceftriaxone and pefloxacin abolished all resistance, whereas the combinations of amikacin plus ceftriaxone or amikacin plus pefloxacin reduced the frequency of resistance by more than half. In animals with P. aeruginosa or S. marcescens infections, resistance to pefloxacin diminished or disappeared after treatment with the combinations of pefloxacin plus ceftriaxone or pefloxacin plus amikacin. However, combinations with ceftriaxone resulted in more frequent resistance to ceftriaxone than did ceftriaxone alone. This was the case in P. aeruginosa infections treated with ceftriaxone plus amikacin (p less than 0.01), and in S. marcescens infections treated with ceftriaxone plus pefloxacin (p less than 0.05). Despite these certain notable exceptions, our data confirm that in most cases combination therapy does limit the emergence of resistance.

Amikacin↗

Emergence of resistance after therapy with antibiotics used alone or combined in a murine model.

A murine model of peritonitis allowing detection and quantification of in-vivo acquired resistance during short term therapy has been used in order to evaluate the capacity of antimicrobial combinations to limit emergence of resistance, as compared to individual components of the regimens. Mice were challenged intraperitoneally with 10(8) cfu of bacteria. Two hours later, a single antibiotic dose was injected subcutaneously: amikacin (15 mg/kg), ceftriaxone (50 mg/kg), pefloxacin (25 mg/kg), amikacin + ceftriaxone, amikacin + pefloxacin or ceftriaxone + pefloxacin. Escherichia coli and Staphylococcus aureus never became resistant. Single drug therapy yielded resistant mutants in Enterobacter cloacae, Serratia marcescens, Klebsiella pneumoniae and Pseudomonas aeruginosa as follows: 74% of ceftriaxone-treated animals, 57% of pefloxacin treated animals and 27% of amikacin treated animals. All the tested combinations reduced the frequency of in-vivo acquired resistance produced by single drugs, and no combination selected resistance when the separate agents of the combination did not. Combining antimicrobial agents limits the risk of emergence of resistance during antibiotic therapy.

Amikacin↗