Biomedical subjects
H A Clasener
Publications and source records attributed to H A Clasener.
Effects of imipenem, cefotaxime and cotrimoxazole on aerobic microbial colonization of the digestive tract.
Superinfections originating from a digestive tract colonized by abnormally high concentrations of aerobic microorganisms as a result of impaired resistance to colonization (CR) may complicate antibiotic therapy. In this study, patients with a moderate to severe systemic infection were randomized to receive either cefotaxime (CTX, n = 10) or cotrimoxazole (CTR, n = 10), 2 antibiotic regimens presumed to spare CR; or imipenem/cilastine (I/C, n = 19). The effect on CR was measured indirectly by comparing the aerobic faecal flora before antibiotic treatment with that on day 8 of treatment. An increase in aerobic faecal flora denotes a disturbed CR, whereas a decrease means that the organism is sensitive to the effective faecal concentration of the antibiotic. Imipenem/cilastine-treated patients showed a significant increase in enterococci and Candida spp., while the number of aerobic Gram-negative rods remained constant. Cefotaxime-treated patients had evidence of an increase in enterococci, but not of Candida spp., and Escherichia coli numbers decreased significantly. In these patients the concentration of other Gram-negative aerobic rods showed a slight increase in 6 patients with a resistant Pseudomonas strain. Cotrimoxazole-treated patients showed a significant decrease in aerobic Gram-negative rods, a significant increase in Candida spp. and no change in enterococci. It is concluded that all 3 antimicrobial agents impair colonization resistance. Whether or not this is followed by overgrowth with resistant micro-organisms depends on the active faecal concentration of the antimicrobial agent and the MIC of the aerobic micro-organisms. The risk of overgrowth of the bowel with resistant Gram-negative bacilli appears to be smaller following cotrimoxazole than following cefotaxime or imipenem/cilastine.
Colonisation of oropharynx with staphylococci after penicillin in neutropenic patients.
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Influence of pefloxacin on microbial colonization resistance in healthy volunteers.
The influence of pefloxacin, 400 mg twice daily for ten days, on microbial colonization resistance was investigated in six healthy volunteers. In three volunteers impairment of colonization resistance was indicated by a significant increase in the faecal concentration of yeasts. In two of them, impairment of colonization resistance was confirmed by facilitation of colonization by a challenge strain of Klebsiella pneumoniae in the early post-treatment period. It is concluded that pefloxacin impairs colonization resistance in some volunteers. However, during pefloxacin therapy, overgrowth by aerobic bacteria is prevented by the very high antimicrobial concentration in faeces, and after therapy it is prevented by rapid restoration of colonization resistance.
Co-trimoxazole impairs colonization resistance in healthy volunteers.
The influence of co-trimoxazole on colonization resistance of the bowel was investigated in six healthy volunteers, by measuring the numbers of indigenous aerobic flora and of a co-trimoxazole resistant challenge strain of Klebsiella pneumoniae. Impairment of colonization resistance of the bowel was shown by a significant increase in the numbers of yeasts in the faeces of five of six volunteers, by a significant increase in the numbers of Gram-negative bacilli in the faeces of two of six volunteers, and by facilitation of colonization of the bowel by the challenge strain in all volunteers. Impairment of colonization resistance of the mouth was shown by the development of glossitis caused by Candida albicans in two volunteers, and by a significant increase in the numbers of yeasts in mouth washings from four volunteers. It is concluded that co-trimoxazole impairs colonization resistance of the gastro-intestinal tract.
Antibiotic prophylaxis of respiratory tract infection in mechanically ventilated patients. A prospective, blinded, randomized trial of the effect of a novel regimen.
The objective of this study was to assess the effect of a novel regimen of antibiotic prophylaxis on the incidence of lower respiratory tract infection in patients requiring prolonged (at least five days) mechanical ventilation. The design was a controlled, prospective, randomized trial, with blinded comparison of the groups regarding the incidence of respiratory tract infection in an intensive care unit of a university hospital. After determination of the APACHE II score for severity of disease, 88 patients were randomly divided in three groups. Twenty-four of these patients did not complete five days of mechanical ventilation, and eight were withdrawn for other reasons. Fifty-six patients (18 in group 1, 21 in group 2, 17 in group 3) completed the study. Patients in both control groups 1 and 2 did not receive antibiotic prophylaxis, but the two groups differed in the antibiotic policy in case of infection. Patients in group 3 received antibiotic prophylaxis consisting of norfloxacin, polymyxin E, and amphotericin B, applied topically in oropharynx and stomach from time of ICU admission until extubation, and intravenous cefotaxime 500 mg three times a day during the first five days of admission. In both control groups, about 90 percent of the patients acquired microbial colonization of oropharynx or stomach. In group 3, only 12 percent and 24 percent of the patients acquired colonization of oropharynx and stomach, respectively (p less than 0.001). This resulted in a reduction of the incidence of lower respiratory tract infection (78 percent in group 1, 62 percent in group 2, 6 percent in group 3 [p = 0.0001]). The regimen of antibiotic prophylaxis studied prevented respiratory tract infection in mechanically ventilated patients. Antibiotic prophylaxis should be considered in all patients expected to require prolonged mechanical ventilation.
Metronidazole-resistant Helicobacter pylori.
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Influence of amoxycillin on microbial colonization resistance in healthy volunteers. A methodological study.
The influence of amoxycillin 500 mg tid on microbial colonization resistance was investigated in 11 healthy volunteers. Analysis was performed in each volunteer individually. In the first five volunteers we investigated the influence of amoxycillin on the faecal concentration of Gram-negative bacilli, enterococci and yeasts and on spontaneously occurring secondary colonization. In the next six volunteers we also investigated the influence of amoxycillin on colonization resistance against amoxycillin-resistant challenge strains, in order to be independent of the accidental presence of resistant Gram-negative bacilli. In three volunteers all indicators employed did not show impairment of the anaerobic flora that provide colonization resistance. In five volunteers impairment of this flora was indicated both by increase of the faecal concentration of aerobic flora and by increase of spontaneously occurring secondary colonization or facilitation of colonization by the challenge strains. However, in the other three volunteers there was no concordance between the investigated indicators of the influence of amoxycillin on colonization resistance. Possible explanations are discussed. It is concluded that increase of the faecal concentration of aerobic flora is a more reliable indicator of impairment of the anaerobic flora that provides colonization resistance than increase of secondary colonization by strains acquired spontaneously or by challenge strains administered deliberately. In one volunteer, who was excluded from the trial, high-level faecal colonization occurred after challenge with Enterobacter cloacae in the pretreatment period.
Influence of cefotaxime on microbial colonization resistance in healthy volunteers.
The influence of cefotaxime 1000 mg given intravenously bd on microbial colonization resistance was investigated in six healthy volunteers. Administration of cefotaxime allowed colonization of the bowel by a resistant challenge strain of Enterobacter cloacae in all volunteers. The faecal concentration of aerobic flora increased significantly in five of six volunteers. In one the numbers of Gram-negative bacilli, enterococci and yeasts also increased. In the other four the faecal concentration of enterococci and yeasts increased, but Gram-negative bacilli did not rise above pre-treatment level. It is concluded that cefotaxime impairs colonization resistance, although to a variable degree. Therefore the term 'selective decontamination' is not fully justified for prophylactic regimens that include cefotaxime.
The contribution of Escherichia coli to microbial colonization resistance.
The contribution of Escherichia coli to the microbial colonization resistance (CR) of the bowel was investigated in six healthy volunteers. Esch. coli was eliminated from faeces by the administration of a low dose (20 mg daily) of pefloxacin. This did not cause an increase in the faecal concentration of aerobic Gram-positive cocci or yeasts, nor did it facilitate colonization of the bowel by a pefloxacin-resistant challenge strain of Klebsiella pneumoniae. Therefore, Esch. coli does not appear to contribute to the microbial CR. After ten days of pefloxacin, clindamycin 300 mg was administered twice daily for 18 days. Clindamycin caused a significant increase in the faecal concentration of enterococci, yeasts and the K. pneumoniae challenge strain, indicating that the study design was suitable to demonstrate disturbance of microbial CR if it occurred.
Decontamination of the bowel by intravenous administration of pefloxacin.
Intravenous administration of pefloxacin 400 mg twice daily rapidly decontaminated the bowel from Gram-negative bacilli in ten healthy volunteers. The faecal concentrations of enterococci and yeasts did not change significantly. Further, pefloxacin did not facilitate colonization of the bowel by a highly resistant challenge strain (Klebsiella pneumoniae, MIC = 56 mg/l). The diffusible faecal concentration of pefloxacin was between 110 and 260 mg/l in all samples from day 3 of treatment onwards. It is concluded that parenteral administration of pefloxacin is very effective for decontamination of the bowel from Gram-negative bacilli and provides reliable prophylaxis against colonization of the bowel by highly resistant Gram-negative bacilli ingested with food.
Prevention of bacterial colonization of the respiratory tract and stomach of mechanically ventilated patients by a novel regimen of selective decontamination in combination with initial systemic cefotaxime.
A novel regimen of selective decontamination (SDD) with initial systemic cefotaxime prevented bacterial colonization of the oropharynx and stomach in mechanically ventilated patients. In a three-group study of all patients receiving prolonged mechanical ventilation, patients in control groups A and B received antibiotics only when infection was present. In group A, antibiotics that disturb colonization resistance (CR) were used. In group B, antibiotics use was restricted to antibiotics not affecting CR. Patients in group C received SDD, consisting of norfloxacin, polymyxin E and amphotericin B, administered via a gastric tube and applied to the oropharynx. Group C patients further received an initial five day course of cefotaxime, 500 mg tid. The lower respiratory tract was colonized with microorganisms on admission in about half of the patients, and this persisted in both control groups. In group C, lower respiratory tract colonization was eliminated in all patients after five days. In both control groups about 90% of the patients acquired microbial colonization of the oropharynx and stomach, mostly with Gram-negative bacilli. In group C, only 12% and 24% of the patients acquired colonization of the oropharynx and stomach respectively (P less than 0.001). The oropharynx and stomach were the major sources of microorganisms causing lower respiratory tract infection in both control groups. In group C, elimination of oropharyngeal and gastric colonization completely prevented lower respiratory tract infection from these sources.
Effect on colonization resistance: an important criterion in selecting antibiotics.
Infections in humans are most often caused by aerobic microorganisms colonizing the digestive tract. Aerobic microorganisms are constantly entering the digestive tract with food, but colonization is resisted by autochthonous anaerobic flora (microbial colonization resistance) and by host-related factors (physiologic colonization resistance). Antibiotics to which the autochthonous anaerobic flora are sensitive and that achieve sufficiently high concentrations at the sites of colonization will reduce colonization resistance. Consequently, resistant aerobic flora of the digestive tract may reach high concentrations, increasing the risk of superinfection. Therefore, when choosing antimicrobial agents for therapy, the effect on colonization resistance should be taken into account. Immunosuppressed hosts and acutely ill patients undergoing mechanical ventilation can be protected from serious infections by eliminating the most dangerous species of the aerobic endogenous flora, leaving colonization resistance intact. This is called selective decolonization. This article summarizes the effects of antimicrobial agents on colonization resistance.
Faecal level of urobilinogen: an indication for the risk of superinfection and of failure of oral anticonception?
The influence of clindamycin, dicloxacillin, minocycline and norfloxacin on the faecal concentration of urobilinogen was investigated. The studied drugs were administered orally in standard dosage for six days to groups of six volunteers. A decrease in faecal concentration of urobilinogen following administration of clindamycin (P less than 0.01) and dicloxacillin (P less than 0.05) was found. The possible predictive value of a decrease of the faecal level of urobilinogen as an indicator for the impairment of microbial colonization resistance and for the risk of failure of oral anticonceptive treatment is discussed. It is suggested that clindamycin and dicloxacillin should not be combined with oral anticonceptive treatment unless more specific investigations have excluded interaction of these drugs with the oestrogen metabolism in the bowel.
Prevention of catheter-associated gram-negative bacilluria with norfloxacin by selective decontamination of the bowel and high urinary concentration.
Oral norfloxacin prevented Gram-negative bacilluria in female patients with hip fractures, who needed medium-term transurethral catheterization. This was shown in a placebo-controlled double-blind study of 34 patients. Seventeen of these received a suspension containing 200 mg norfloxacin and 500 mg amphotericin B, twice daily. In the placebo group, six cases of Gram-negative bacilluria had occurred by day 7, as compared with no cases during a median time of catheterization of 23 days in the group on medication. Bacteriuria, either by Gram-positive cocci or by Gram-negative bacilli, was observed in 50% of patients on placebo by day 7; in the treatment group this was the case by day 17 (P less than 0.001). Subsequent bacteriuria with Gram-positive cocci was eliminated by nitrofurantoin (50 mg qid) within four days. Norfloxacin is very suitable for the prevention of Gram-negative bacilluria, because it decontaminates Gram-negative bacilli from the bowel, reaches high concentrations in urine and rarely produces resistant variants.
Influence of cefaclor, phenethicillin, co-trimoxazole and doxycycline on colonization resistance in healthy volunteers.
The influence of oral administration of cefaclor, phenethicillin, co-trimoxazole and doxycycline on colonization resistance (CR) of the oropharynx and colon in healthy volunteers was studied. Antimicrobial agents were administered in a randomized cross-over design. No effect on CR of the oropharynx could be demonstrated. Phenethicillin decreased CR of the colon against Enterobacteriaceae (P = 0.001). Co-trimoxazole significantly decreased the concentration of Enterobacteriaceae in faeces (P = 0.03) but the decrease caused by cefaclor and doxycycline did not reach statistical significance. Administration of antimicrobial agents increased the appearance of secondary colonization by Enterobacteriaceae in faeces, especially when Escherichia coli was eliminated. During administration of phenethicillin, secondary colonization occurred at a concentration exceeding 10(7)/g in some volunteers. Following administration of cefaclor, co-trimoxazole and doxycycline, elimination of E. coli may result in the substitution by resistant Gram-negative bacilli in low concentrations.
Prophylaxis of infection by selective decontamination in mechanically ventilated patients. A preliminary report.
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Colonization resistance: a guide to antibiotic policy in the ICU.
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