Ludo Verbist

Randomized, controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multidisciplinary intensive care unit.

OBJECTIVEnTo evaluate the efficacy of two regimens of selective decontamination of the digestive tract in mechanically ventilated patients.nnnDESIGNnProspective, randomized, concurrent trial.nnnSETTINGnMultidisciplinary intensive care unit (ICU) in a 1,800-bed university hospital.nnnPATIENTSnConsecutive patients (n = 660) who were likely to require mechanical ventilation for at least 48 hrs were randomized to one of three groups: conventional antibiotic regimen (control group A); oral and enteral ofloxacin-amphotericin B (group B); and oral and enteral polymyxin E-tobramycin-amphotericin B (group C). Both treatment groups received systemic antibiotics for 4 days (ofloxacin in group B and cefotaxime in group C).nnnINTERVENTIONSnPatients were randomized to receive standard treatment (control group A, n = 220), selective decontamination regimen B (group B, n = 220), and selective decontamination regimen C (group C, n = 220). After early deaths and exclusions from the study, 185 controls (group A) and 193 (group B)/200 (group C) selective decontamination regimen patients were available for analysis.nnnMEASUREMENTS AND MAIN RESULTSnMeasurements included colonization and primary/secondary infection rate, ICU mortality rate, emergence of antibiotic resistance, length of ICU stay, and antimicrobial agent costs. The study duration was 19 months. The patient groups were fully comparable for age, diagnostic category, and severity of illness. One third of patients in each group suffered a nosocomial infection at the time of admission. There was a significant difference between treatment group B and control group A in the number of infected patients (odds ratio of 0.42, 95% confidence interval of 0.27 to 0.64), secondary lower respiratory tract infection (odds ratio of 0.47, 95% confidence interval of 0.26 to 0.82), and urinary tract infection (odds ratio of 0.47, 95% confidence interval of 0.27 to 0.81). Significantly more Gram-positive bacteremias occurred in treatment group C vs. group A (odds ratio of 1.22, 95% confidence interval 0.72 to 2.08). Infection at the time of admission proved to be the most significant risk factor for subsequent infection in control and both treatment groups. ICU mortality rate was almost identical (group A 16.8%, group B 17.6%, and group C 15.5%) and was not significantly related to primary or secondary infection. Increased antimicrobial resistance was recorded in both treatment groups: tobramycin-resistant enterobacteriaceae (group C 48% vs. group A 14%, p < .01), ofloxacin-resistant enterobacteriaceae (group B 50% vs. group A 11%, p < .02), ofloxacin-resistant nonfermenters (group B 81% vs. group A 52%, p < .02), and methicillin-resistant Staphylococcus aureus (group C 83% vs. group A 55%, p < .05). Antimicrobial agent costs were comparable in control and group C patients; one third less was spent for group B patients.nnnCONCLUSIONSnIn cases of high colonization and infection rates at the time of ICU admission, the preventive benefit of selective decontamination is highly debatable. Emergence of multiple antibiotic-resistant microorganisms creates a clinical problem and a definite change in the ecology of environmental, colonizing, and infecting bacteria. The selection of multiple antibiotic-resistant Gram-positive cocci is particularly hazardous. No beneficial effect on survival is observed. Moreover, selective decontamination adds substantially to the cost of ICU care.

GR-20263: a new aminothiazolyl cephalosporin with high activity against Pseudomonas and Enterobacteriaceae.

The in vitro activity of GR-20263, a new aminothiazolyl cephalosporin, was compared with the activities of other beta-lactam antibiotics by using 800 clinical bacterial isolates. GR-20263 was highly active (inhibition of 90% of the isolates between 0.03 and 1 microgram/ml) against the common Enterobacteriaceae and 5 to 20 times more active than cefuroxime, cefoxitin, and cephalothin. GR-20263 was three to six times less active than cefotaxime against Escherichia coli, Klebsiella pneumoniae, Salmonella, and Shigella, but three to four times more active than cefotaxime against Proteus vulgaris and Serratia marcescens. The activity of GR-20263 against Pseudomonas aeruginosa (with minimal inhibitory concentrations of 2 and 8 micrograms/ml for 90 and 100% of the isolates, respectively) was similar to that of tobramycin, 2 times that of cefsulodin, 5 times that of piperacillin, and 10 times that of cefotaxime. Against Haemophilus influenzae GR-20263 was three time more active than ampicillin. The beta-lactamase-producing strains were as susceptible to GR-20263 as the beta-lactamase-negative strains. GR-20263 was less active than cefotaxime and ampicillin against Staphylococcus aureus.

Surveillance of Human Yersinia enterocolitica Infections in Belgium: 1967–1996

Between 1967 and 1996, > 18,700 strains of Yersinia species, excluding Yersinia pestis, were recovered in Belgium from a variety of gastrointestinal and extraintestinal sites in patients. Full identification and serotyping were performed by the two Belgian reference laboratories. Yersinia enterocolitica serogroup O:3 predominated (79.4% of strains), followed by serogroup O:9 (11.1%). The remaining 9.5% of isolates belonged to serogroups and related species generally considered nonpathogenic. Acute enterocolitis was the most common clinical form of Y. enterocolitica infection, affecting primarily children younger than 5 years of age. Since 1967, there was a steady increase in isolations every year, with 305 cases in 1975 and up to 1,469 in 1986. From 1987 on, there was a clear decrease in the number of reported cases, although the number of participating laboratories and culture techniques remained constant. This significant decrease in the occurrence of Y. enterocolitica infections may be explained by changes in the slaughtering procedures and eating habits of the population.

In vitro activity of N-formimidoyl thienamycin in comparison with cefotaxime, moxalactam, and ceftazidime.

The in vitro activity of N-formimidoyl thienamycin (N-f-thienamycin) was compared with the activities of other B-lactam antibiotics, using over 500 clinical bacterial isolates. N-f-Thienamycin inhibited 90% of the isolates of the common Enterobacteriaceae between 0.006 and 2 microgram/ml, regardless of their resistance to amoxicillin, ticarcillin, or cephalothin. It was, however, fourfold less active than moxalactam and ceftazidime and eightfold less active than cefotaxime. N-f-Thienamycin was nearly as active as ceftazidime against Pseudomonas aeruginosa (mean minimal inhibitory concentration, 3.0 microgram/ml) and eightfold more active than cefotaxime and moxalactam. In contrast to cefotaxime, moxalactam, and ceftazidime, N-f-thienamycin was highly active against enterococci (mean minimal inhibitory concentration, 1.3 microgram/ml) and staphylococci. The oxacillin-susceptible Staphylococcus aureus were inhibited between 0.03 and 0.12 microgram/ml, and the oxacillin-resistant S. aureus were inhibited between 0.12 and 2 microgram/ml. The high activity of N-f-thienamycin against both of the most important gram-positive and gram-negative organisms makes it a very promising new antibiotic.

Capsular types and antibiotic sensitivity of pneumococci isolated from patients with serious infections in Belgium 1980 to 1988

A total of 2,765 strains ofStreptococcus pneumoniae isolated in more than 60 Belgian laboratories from blood or normally sterile body fluids between 1 November 1980 and 31 December 1988 were serotyped. From January 1983 onwards susceptibility of the strains to antimicrobial agents was also tested. The 2,765 isolates belonged to 57 of the 84 currently identified serotypes. Overall, 94 % of the strains were represented in the current 23-valent vaccine. The remaining 6 % of strains were distributed among 18 serotypes. More than 84 % of the middle ear fluid isolates came from children under ten years. Meningitis was commonest in children under five years and in adults over sixty years. Two-thirds of pneumococcal bacteremia isolates came from patients over 50 years. Of 1,933 isolates tested for susceptibility to antibiotics, 335 (17 %) were resistant to one or more of the agents tested (tetracycline, erythromycin, chloramphenicol, penicillin). Only 19 strains were relatively resistant to penicillin, while six were fully resistant. Resistance to erythromycin increased significantly from 5.2 % in 1986 to 11.5 % in 1988. The resistance ofStreptococcus pneumoniae to other antimicrobial agents did not change significantly during the study period. There was no relationship between age group and resistance to any of the agents tested.

Norfloxacin versus thiamphenicol for treatment of uncomplicated gonorrhea in Rwanda.

In an open prospective study, single oral doses of norfloxacin (800 mg) and thiamphenicol (2.5 g) were used to treat, respectively, 122 and 46 consecutive patients with uncomplicated gonorrhea. Neisseria gonorrhoeae was eradicated from 119 (97.5%) patients treated with norfloxacin and from 35 (76.0%) patients treated with thiamphenicol. Norfloxacin treatment failure was not related to drug resistance or to insufficient absorption of the drug. Thiamphenicol failure correlated with low in vitro susceptibility of the infecting strain. In a single oral dose of 800 mg, norfloxacin appeared to be an excellent alternative treatment regimen for uncomplicated gonorrhea in an area with a high prevalence of penicillin-resistant gonococci.

In vitro activity of Ro 13-9904, a new beta-lactamase-stable cephalosporin.

The minimal inhibitory concentration (MIC) of Ro 13-9904 against 245 clinical isolates was determined by an agar dilution method. The activity of Ro 13-9904 against most Enterobacteriaceae was similar to that of cefotaxime; it was slightly more active than cefotaxime against Proteus mirabilis, Providencia species, and Serratia marcescens, but slightly less active against Klebsiella species. Ro 13-9904 was twofold more active than cefotaxime and threefold more active than ticarcillin against ticarcillin-susceptible Pseudomonas aeruginosa, with a mean MIC of 7.2 micrograms/ml; isolates highly resistant to ticarcillin were inhibited by a mean MIC of 17.2 micrograms/ml. Ro 13-9904 was fourfold more active than ampicillin against susceptible Haemophilus influenzae and was equally active against beta-lactamase-producing isolates. Ro 13-9904 was highly active against pneumococci and moderately active (MIC, 4 micrograms/ml) against Staphylococcus aureus isolates, whether they were susceptible or resistant to penicillin G. Oxacillin-resistant S. aureus and Streptococcus faecalis were completely resistant to Ro 13-9904 (MIC, greater than 128 micrograms/ml).

Effect of temocillin in combination with other beta-lactam antibiotics.

The antibacterial interactions of temocillin with other beta-lactams were tested by checkerboard combination in Mueller-Hinton agar against 146 strains of members of the family Enterobacteriaceae, 35 Pseudomonas aeruginosa strains, and 35 Staphylococcus aureus strains. Most combinations showed a moderate degree of synergism. In only one Klebsiella strain was minor antagonism observed between temocillin and ampicillin.

In vitro activity of the new ketolide telithromycin and other antibiotics against Streptococcus pneumoniae in Belgium

Abstract In Belgium more than 17 % of the invasive pneumococci are not susceptible to penicillin, and more than 38 % not to macrolides. The most prevalent mechanism of macrolide resistance in Europe is modification of the drug target site leading to cross-resistance to lincosamides and group B streptogramines (MLSB resistance). Telithromycin is the first antibiotic of the family of ketolides, which differ from erythromycin by having a 3-keto group instead of the neutral sugar L-cladinose. We tested the susceptibility of 637 pneumococci, recently isolated from patients in Belgium, to telithromycin and five other antibiotics. Data generated by this study show that telithromycin inhibits 98.4 % of pneumococci at a breakpoint concentration of 1 mg/L in spite of a high percentage ( >30 %) of strains with the MLSB constitutive type of resistance. Susceptibilities to the five comparator drugs were : penicillin (81.8 %), tetracycline (67.0 %), levofloxacin (98.9 %), erythromycin (61.5 %) and clindamycin (66.6 %). Consequently telithromycin looks to have considerable potential for the empiric treatment of community-acquired respiratory tract infections.

In Vitro Activity of Cefonicid Compared to Other Antibiotics Against Clinical Bacterial Isolates

The in vitro activity of cefonicid compared to that of other antibiotics has been evaluated against 401 Enterobacteriaceae, 20 H. influenzae, 17 Branhamella catarrhalis and 71 staphylococci. Cefonicid was always more active than cefazolin, and usually more active than cefamandole and cefuroxime against susceptible gram-negative organisms (E. coli, P. mirabilis, Klebsiella, Shigella, Salmonella, H. influenzae). Cefonicid was ineffective against most strains of Enterobacter, Citrobacter, S. marcescens and M. morganii. Staphylococci were 6 to 8 times less susceptible to cefonicid than to the other cephalosporins.