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Biomedical subjects

M Walder

Publications and source records attributed to M Walder.

At least 37 records · Page 2Linked to original sources
PubMed1993

Interactions of drugs acting against Staphylococcus aureus in vitro and in a mouse model.

Two combinations of antibiotics, clindamycin with rifampicin and cloxacillin with netilmicin, were investigated for their activity against two strains of Staphylococcus aureus (a sensitive reference strain and a methicillin-resistant clinical isolate) by means of the in vitro checkerboard technique and an in vivo infected mouse model. The mouse model allowed drug interactions to be evaluated both from the changes in the number of bacteria surviving treatment and from the measured exposure to antibiotics at the site of infection. Specimens from the latter were evaluated twice (day 0 and day 2) in each experiment. The combination of cloxacillin and netilmicin exhibited a synergistic effect against the reference strain both in vitro and in vivo, whereas synergism was obtained under in vitro conditions only against the methicillin-resistant strain. The clindamycin and rifampicin combination acted synergistically or indifferently against both strains in vitro and at day 0 of the in vivo experiments. In contrast, on day 2 of infection, this combination had significantly greater bactericidal effect (synergism) compared to the combination of cloxacillin and netilmicin. These results illustrate the difficulties of interpreting in vitro results for clinical use.

Animals↗
PubMed1993

Penetration of penicillin V to tonsillar surface fluid in healthy individuals and in patients with acute tonsillitis.

In the treatment of group A streptococcal tonsillitis, as the bacteria are located on the epithelial surface, an important determinant of outcome is the concentration of penicillin in extracellular tonsillar surface fluid. Accordingly, we investigated the concentration of penicillin in serum, and penetration to tonsillar surface fluid and saliva in nine patients with acute group A streptococcal tonsillitis and in nine healthy controls. Among the healthy subjects, despite high serum penicillin concentrations (mean, 2.04 micrograms/ml), there was no penetration to tonsillar surface fluid or to saliva, whereas erythromycin penetrated to tonsillar surface fluid in 3/6 cases. Of the nine patients with acute tonsillitis, on the first day of treatment eight manifested high concentrations of penicillin in tonsillar surface fluid (mean, 0.34 micrograms/ml--i.e. well above the minimal inhibitory concentration (MIC) for group A streptococci), but penetration to saliva was found in only two patients. On the tenth day of treatment, penicillin was not present in the saliva of any of the patients and was present in the tonsillar surface fluid of only one. The results suggest that measurable concentrations of penicillin in tonsillar surface fluid can only be obtained in the presence of inflammation with fluid exudation through the tonsillar epithelium.

Adult↗
PubMed1992

Pharmacokinetics of ceftazidime in acutely ill hospitalised elderly patients.

The i.v. and i.m. dose pharmacokinetics of ceftazidime 1 g b.i.d. were investigated in steady state in 52 consecutive cases of hospitalised patients with underlying diseases and serious supervening bacterial infections. Following i.v. bolus injection, serum concentrations of greater than 4 mg/l persisted for 8 h in all patients. Compared to values found in younger patients studied previously, clearance was markedly reduced in the elderly, t1/2 beta more than doubled, the area under the curve four times enlarged and the apparent volume of distribution reduced. The values obtained in serum after i.m. injection were similar, though the peak concentration was delayed by about 2 h. The serum uptake was approximately 70%, and serum concentration was greater than 4 mg/l for 8 h. The concentrations in tissue fluid after i.v. administration were similar to those in serum, but the penetration into tissue fluid was slower and only 20% of that reported previously for young people. The elimination was slow, with greater than 4 mg/l maintained for 7 h. Tissue concentrations after i.m. injection were almost comparable with those after i.v. injection, but lagged behind by about 1 h. In conclusion, suitable concentrations in blood and tissue are attained with 1 g ceftazidime b.i.d., whether administered by the i.v. or i.m. route.

Aged↗
PubMed1991

Septicaemia caused by unusual Campylobacter species (C. laridis and C. mucosalis).

Two cases of campylobacter septicaemia are described. The first, caused by Campylobacter laridis was associated with gastroenteritis and occurred in a healthy individual. In the second case, a catalase negative species, C. mucosalis was isolated from blood in an immunocompromised patient with symptoms of pneumonia. Both campylobacter strains grew faintly under the routine culture conditions used. Improved diagnostic procedures for Campylobacter species may thus be warranted.

Adult↗
PubMed1990

Air contamination during total hip arthroplasty in an ultraclean air enclosure using different types of staff clothing.

Air contamination was measured in a down-flow, clean air enclosure during 50 total hip arthroplasties to compare the effect of different scrub suits and operating gowns. In one series, with cotton clothes, the operating gowns used were either disposable nonwoven operating gowns or total body exhaust gowns. With the exhaust gowns the median air contamination, measured as colony-forming units (cfu)/m3, was reduced by about 5 times, to 0.3. In another series, nonwoven operating gowns were used together with scrub suits made of either cotton or one of two types of synthetic materials. The latter two scrub suits were equipped with elastic sealings at the openings. With both of these types the median air contamination, compared to cotton scrub suits, was reduced by about one half, to 0.4 cfu/m3. The authors conclude that both specially designed scrub suits and exhaust gowns can further reduce an already low level of bacterial air contamination in a down-flow, clean air enclosure.

Air Microbiology↗
PubMed1990

Does administration of an aminoglycoside in a single daily dose affect its efficacy and toxicity?

Treatment efficacy, oto- and nephrotoxicity, and aminoglycoside pharmacokinetics were evaluated in a prospective, comparative, randomized clinical study of aminoglycosides given once a day or three times a day for severe infections. Sixty patients were treated with netilmicin or gentamicin 4.5 mg/kg bodyweight/day, either once a day or divided into three doses a day. The patients were allocated randomly to the different groups. The clinical effect was difficult to compare in the different groups, because of the small numbers of patients. Therapeutic failures were seen in seven patients (three after one and four after three doses per day). Two patients, one with Staphylococcus aureus endocarditis and one with streptococcal endocarditis, on netilmicin once daily and conventional high-dose therapy with a penicillin had positive blood cultures after five and seven days of treatment, respectively. Vestibular function and hearing acuity were examined by serial audiograms and electronystagmograms. In spite of extensive diagnostic evaluation, only two cases of ototoxicity were detected. One patient treated with gentamicin three times a day developed vertigo and a severe abnormality of her electronystagmogram. One young patient treated with gentamicin once daily had a slight bilateral reduction of hearing. Nephrotoxicity was mild and did not differ in the four treatment groups. This was the first investigation of a once-daily dosing regimen conducted in seriously ill patients with systemic infections. We could not demonstrate any evidence that aminoglycoside treatment once daily has greater oto- or nephrotoxicity than the traditional three times daily regimen.

Audiometry↗
PubMed1989

A method to evaluate the cleaning and disinfectant action of surface disinfectants.

Surface disinfection tests, used to evaluate new disinfectants, do not take into account the effects of detergents or of the mechanical cleaning process. We describe methods which evaluate both the disinfection and cleaning effect of disinfectants on organic matter. When testing alcohols at high concentrations (greater than or equal to 70%) on blood spots contaminated with Staphylococcus aureus, we found that the organisms were trapped and fixed to the test surface, probably due to denaturation of the blood. This gave a low inactivating factor (IF), as well as a poor subjective cleaning effect (SC). If serum was used instead of blood, we observed less pronounced trapping, resulting in a high IF although the SC was still poor. When broth was used, both IF and SC were satisfactory. With alcohols at a concentration of 42%, trapping was markedly reduced which improved the SC in blood contamination, with serum or broth contamination trapping did not occur. However, 42% ethanol lost its killing effect (i.e. low IF), whereas 42% isopropanol still demonstrated a high IF.

Bacteria↗
PubMed1989

The role of beta-lactamase in mixed infections in mice in relation to treatment with ampicillin.

Beta-lactamase-producing Staphylococcus aureus and Bacteroides fragilis in a localized mixed infection has been found to degrade the beta-lactam antibiotic at the focus of infection, thus protecting both the bacteria and pathogens susceptible to the antibiotic. To determine if beta-lactamase produced by Hemophilus influenzae and Branhamella catarrhalis have similar importance in mixed infections, a thread infection model in mice was used to evaluate the capacity of beta-lactamase produced by S. aureus, B. catarrhalis, or H. influenzae to hydrolyze ampicillin in a mixed infection with Streptococcus pneumoniae in mice. For both S. aureus and B. catarrhalis, the ampicillin concentrations at infection sites where beta-lactamase was produced were lower than at sites where beta-lactamase was not produced; however, this difference was not found when clavulanic acid was added to the ampicillin. In mixed infections with strains that did not produce beta-lactamase, ampicillin concentrations were similar with or without clavulanic acid. S. aureus was the best "protector" followed by B. catarrhalis. The beta-lactamase produced by H. influenzae failed to protect the S. pneumoniae. No bactericidal effect of clavulanic acid was found.

Ampicillin↗
PubMed1989

Postantibiotic effects of imipenem, norfloxacin, and amikacin in vitro and in vivo.

The postantibiotic effects (PAEs) of imipenem and norfloxacin were tested against Staphylococcus aureus, Streptococcus (Enterococcus) faecalis, Escherichia coli, and Pseudomonas aeruginosa. Amikacin was tested against the same bacteria except Streptococcus faecalis. For in vitro tests, a viable count-washing method was used, and for in vivo tests, the thread technique in normal mice was used. All three drugs produced PAEs of 1.1 to 3.8 h in vitro and 1.4 to 4.3 h in vivo against the pathogens tested. In vitro and in vivo results correlated well. The PAE had a significantly (P less than 0.01 to 0.001) longer duration in vivo than in vitro, but the PAE of imipenem on Staphylococcus aureus was longer in vitro. The PAE was not due to residual antibiotics at the site of infection, and no PAE was obtained if at any time the antibiotic concentration at the infection site reached the MIC for the pathogen tested. The results indicate that the presence of a PAE may enable antibiotics to be given more intermittently without a loss of efficacy and that the PAE can only be induced if the level of the antibiotic exceeds the MIC for the pathogen in question for at least several minutes.

Amikacin↗
PubMed1989

No effect of omeprazole-induced hypoacidity on the bioavailability of amoxycillin or bacampicillin.

The absorption of ampicillin esters is reported to decrease when gastric acidity is inhibited because of hydrolysis of the esters, or by lowered solubility at a higher pH. No such information on the hydroxylated derivative amoxycillin is available. This was investigated in 8 fasting volunteers, who received 800 mg bacampicillin or 1000 mg amoxycillin on 4 study days, separated by at least 1 week. Each ampicillin derivative was administered on 1 occasion as a single drug, and on another after 1 week's pretreatment with the potent acid inhibitor omeprazole. Bacampicillin was absorbed more rapidly than amoxycillin, and serum peak concentrations were higher. After induced hypoacidity, peak concentrations of both antibiotics appeared to be slightly delayed, and those of bacampicillin significantly reduced. Nevertheless, both the areas under the plasma concentration curves, and the half lives of elimination of the antibiotics were unaffected. Hypoacidity as such does not reduce the bioavailability of amoxycillin or bacampicillin.

Adult↗
PubMed1989

Occlusive clothing and ultraviolet radiation in hip surgery.

In a randomized study of 20 total hip arthroplasties, the staff wore shirts and trousers of a fabric impervious to bacteria underneath operating gowns of a non-woven material. Volumetric air sampling demonstrated a low number of colony-forming units with this clothing, further reduced by ultraviolet radiation to below 10 colony-forming units/m3, the upper limit of "ultraclean air," in all the cases (median 2.6, range 1.1-7.1).

Air Microbiology↗
PubMed1988

[Dose-response curve and preliminary clinical study of a laxative, lactilol].

15 women complaining of chronic constipation were included in a prospective open trial to determine the laxative action and minimal effective dose of lactitol. Through the administration of increasing doses, an ED50 of 0.25 g/kg/day, was established. During a 15-day treatment period at the minimal effective dose, all patients had reduced symptoms of constipation as compared with a previous 15-day control period. Side effects of minor intensity were frequently recorded (flatulence, rumblings, wind, and, less frequently, abdominal cramps or nausea). Thus, the use of lactitol for symptomatic treatment of constipation deserves further clinical studies to determine better its indications and benefit.

Adult↗
PubMed1988

Mouse model for evaluation of antibiotic treatment of acute and chronic infections.

A thread model is presented which enables the simultaneous evaluation of bactericidal rate and antibiotic concentration at the site of infection in mice. Ampicillin and netilmicin were tested against both gram-positive and gram-negative bacteria. With the doses tested there was substantial drug penetration into the site of infection immediately after initiation of infection (day 0), whereas the drug penetration on days 2 and 6 of infection was delayed and reduced. On day 0 of infection there was significant bactericidal effect, but little or no effect could be demonstrated on days 2 and 6 of infection, even though drug concentrations close to the MBC values for several drug/bacteria combinations were reached. The model reflects the treatment situations for the acute and the chronic infection and may be of help in evaluating the efficacy of the drug at the site of infection.

Acute Disease↗
PubMed1988

Antibiotic resistance of coagulase-negative staphylococci in an orthopaedic department.

Coagulase-negative staphylococci (CNS) were cultured from the anterior nares of surgeons, theatre and ward staff, and from patients before and 2 weeks after a total hip replacement. The CNS found in ward staff were more resistant to antibiotics than those in surgeons and theatre staff. Methicillin resistance of CNS in patients increased from 4 to 31% following surgery. Gentamicin-resistant CNS were only found postoperatively, in 20% of patients, in most of whom gentamicin-loaded acrylic bone cement was used.

Anti-Bacterial Agents↗
PubMed1988

A mouse model for simultaneous pharmacokinetic and efficacy studies of antibiotics at sites of infection.

Tissue penetration may be an important pharmacokinetic determinant to achieve the chemotherapeutic efficacy of antimicrobial agents. We describe a mouse model for the simultaneous study of antibiotic kinetics and efficacy at the site of infection. With the doses tested there was no difference in drug penetration into healthy tissue and tissue at the site of acute bacterial infection. Ampicillin and netilmicin levels over the minimal inhibitory concentration (MIC) were needed to produce significant bacterial killing. During the 6 h observation period susceptible Gram-positive bacteria were eradicated whereas Gram-negative bacteria were reduced in number but not eradicated, even though the antibiotic concentrations exceeded minimal bactericidal concentration (MBC) three times.

Ampicillin↗
PubMed1988

Long-term effects on bacterial sensitivity patterns of preoperative antibiotic prophylaxis in colorectal surgery.

Since 1973, when doxycycline was introduced as preoperative prophylaxis in elective colorectal surgery at Malmö General Hospital, Sweden, there has been an unchanged and low rate (8% to 12%) of septic complications in colonic surgery. For treatment of postoperative infections, ampicillin and cefuroxime have been used since 1973 and 1980, respectively. The sensitivity of Escherichia coli to these three antibiotics used for prophylaxis and treatment was followed for five years (1981-1985). Only minor changes were observed during the period. A lower frequency of antibiotic resistance was found in bacterial strains isolated peroperatively than in strains isolated postoperatively after colorectal surgery or from infections in other patients. Considering the low frequency of postoperative infectious complications and the low frequency of antibiotic resistance in peroperative isolates, doxycycline still remains an alternative for prophylaxis in bowel surgery.

Anti-Bacterial Agents↗
PubMed1988

No effect of oral N-acetylcysteine on the bioavailability of erythromycin and bacampicillin.

In vitro studies with N-acetylcysteine (NAC) solutions used for inhalation treatment have demonstrated inactivation of some antibiotics by NAC. Oral NAC treatment is increasingly common for long-term prophylaxis in chronic bronchitis. During exacerbations, treatment with oral antibiotics will often be given simultaneously. We assessed the effect of simultaneous oral administration of NAC on the bioavailability of two antibiotics in ten healthy volunteers. No effect of NAC was found on the bioavailability of ampicillin, after administration of the prodrug bacampicillin. A slight, but not significant statistical increase in erythromycin serum levels was seen with NAC. Acetylator phenotype did not influence the absorption of NAC, which seemed slightly reduced by bacampicillin, but significantly increased by erythromycin. No decrease of antibacterial activity of sera was found in vitro after the addition of NAC or the related thiol glutathione, employing micrococcus luteus and staphylococcus aureus as indicator organisms.

Acetylcysteine↗