Inga Odenholt

Lactobacillus plantarum 299v for the Treatment of Recurrent Clostridium difficile-associated Diarrhoea: A Double-blind, Placebo-controlled Trial

A double-blind, placebo-controlled trial was performed to analyse the ability of Lactobacillus plantarum 299v to prevent further recurrent episodes of Clostridium difficile-associated diarrhoea (RCDAD). Recurrence of clinical symptoms (main outcome) was seen in 4 of 11 patients who received metronidazole in combination with L. plantarum 299v and in 6 of 9 treated with metronidazole in combination with placebo. The lactobacilli treatment had no side-effects. Although the small sample size does not allow any conclusion to be drawn concerning the efficacy of L. plantarum in patients with RCDAD, these results may contribute to the ongoing discussion about the benefits of probiotics in patients with RCDAD and encourage the performance of larger multicentre studies.

Extended-spectrum beta-lactamase-producing Escherichia coli in patients with travellers' diarrhoea.

Abstract The identification of patients carrying extended-spectrum beta-lactamase (ESBL)-producing bacteria is important, since these patients are at risk of receiving inappropriate empirical therapy if they become infected. The purpose of this study was to investigate the occurrence of ESBL-producing bacteria in patients with travellers’ diarrhoea. Patients with travellers’ diarrhoea (N = 242) having delivered stool samples for the diagnosis of Salmonella, Shigella, Yersinia or Campylobacter, were also examined for ESBL-producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. The overall prevalence of faecal carriage of ESBL-producing bacteria was 24% (58/242). Of the patients who had travelled in Europe, 3% (2/63) were found to be ESBL carriers in comparison to 36% (50/138) of those who had travelled outside Europe. ESBL-producing E. coli was especially common among patients returning from India (11/14), Egypt (19/38; 50%) and Thailand (8/38; 22%). In total, 90% of the genes of the ESBL-positive samples were of CTX-M type. The CTX-M-1 group dominated, followed by the CTX-M-9 group. The repetitive sequence-based PCR fingerprint pattern showed that there was no similarity between the ESBL strains found. Patients who have travelled outside Europe are at high risk of being colonized with ESBL-producing Enterobacteriaceae, and, if infected, are also at risk of receiving inappropriate empirical antibiotic therapy.

Activity of three disinfectants and acidified nitrite against Clostridium difficile spores.

OBJECTIVE To identify environmentally safe, rapidly acting agents for killing spores of Clostridium difficile in the hospital environment. DESIGN Three classic disinfectants (2% glutaraldehyde, 1.6% peracetyl ions, and 70% isopropanol) and acidified nitrite were compared for activity against C. difficile spores. Four strains of C. difficile belonging to different serogroups were tested using a dilution-neutralization method according to preliminary European Standard prEN 14347. For peracetyl ions and acidified nitrite, the subjective cleaning effect and the sporicidal activity was also tested in the presence of organic load. RESULTS Peracetyl ions were highly sporicidal and yielded a minimum 4 log10 reduction of germinating spores already at short exposure times, independent of organic load conditions. Isopropanol 70% showed low or no inactivation at all exposure times, whereas glutaraldehyde and acidified nitrite each resulted in an increasing inactivation factor (IF) over time, from an IF greater than 1.4 at 5 minutes of exposure time to greater than 4.1 at 30 minutes. Soiling conditions did not influence the effect of acidified nitrite. There was no difference in the IF among the 4 strains tested for any of the investigated agents. Acidified nitrite demonstrated a good subjective cleaning effect and peracetyl ions demonstrated a satisfactory effect. CONCLUSIONS Cidal activity was shown against C. difficile spores by glutaraldehyde, peracetyl ions, and acidified nitrite. As acidified nitrite and peracetyl ions are considered to be environmentally safe chemicals, these agents seem well suited for the disinfection of C. difficile spores in the hospital environment.

Pharmacodynamics of Telithromycin In Vitro against Respiratory Tract Pathogens

ABSTRACT Telithromycin (HMR 3647) is a new ketolide that belongs to a new class of semisynthetic 14-membered-ring macrolides which have expanded activity against multidrug-resistant gram-positive bacteria. The aim of the present study was to investigate different basic pharmacodynamic properties of this new compound. The following studies of telithromycin were performed: (i) studies of the rate and extent of killing of respiratory tract pathogens with different susceptibilities to erythromycin and penicillin exposed to a fixed concentration that corresponds to a dose of 800 mg in humans, (ii) studies of the rate and extent of killing of telithromycin at five different concentrations, (iii) studies of the rate and extent of killing of the same pathogens at three different inocula, (iv) studies of the postantibiotic effect and the postantibiotic sub-MIC effect of telithromycin, and (v) determination of the rate and extent of killing of telithromycin in an in vitro kinetic model. In conclusion, telithromycin exerted an extremely fast killing of all strains of Streptococcus pneumoniae both with static concentrations and in the in vitro kinetic model. A slower killing of the strains of Streptococcus pyogenes was noted, with regrowth in the kinetic model of a macrolide-lincosamide-streptogramin B-inducible strain. The strains ofHaemophilus influenzae were not killed at all at a concentration of 0.6 mg/liter due to high MICs. A time-dependent killing was seen for all strains. No inoculum effect was seen for the strains of S. pneumoniae, with a 99.9% reduction in the numbers of CFU for all inocula at both 8 h and 24 h. The killing of the strains of S. pyogenes was reduced by 1 log10 CFU at 8 h and 2 to 3 log10 CFU at 24 h when the two lower inocula were used but not at all at 8 and 24 h when the highest inoculum was used. For both of the H. influenzae strains there was an inoculum effect, with 1 to 2 log10 CFU less killing for the inoculum of 108CFU/ml in comparison to that for the inoculum of 106CFU/ml. Overall, telithromycin exhibited long postantibiotic effects and postantibiotic sub-MIC effects for all strains investigated.

Upper respiratory tract infections in general practice: diagnosis, antibiotic prescribing, duration of symptoms and use of diagnostic tests

A diagnosis/antibiotic prescribing study was performed in 5 counties in Sweden for 1 week in November 2000. As part of this study, the characteristics and clinical management of patients with upper respiratory tract infections (n = 2899) in primary care were analyzed. Almost half of the patients were aged < 15 y and one-fifth of the patients consulted out of hours. Of all patients seeking primary care for upper respiratory tract infections, 56.0% were prescribed an antibiotic. Almost all patients who were given the diagnoses streptococcal tonsillitis, acute otitis media or acute sinusitis were prescribed antibiotics, compared to 10% of patients with common cold or acute pharyngitis. The most frequently prescribed antibiotic was penicillin V (79.2%) and this was even more pronounced out of hours, when the diagnoses otitis media and streptococcal tonsillitis were more frequently used. In patients with common cold and acute pharyngitis, the percentage who received antibiotics increased with increasing length of symptoms and increasing CRP levels. In patients with acute pharyngitis or streptococcal tonsillitis, antibiotics were prescribed less frequently provided streptococcal tests were performed. The management of patients with upper respiratory tract infections in general practice seems to be in good agreement with current Swedish guidelines. However, the study indicates some areas for improvement. The diagnosis of acute sinusitis seems to have been overestimated and used only to justify antibiotic treatment.

Diagnosis-prescribing surveys in 2000, 2002 and 2005 in Swedish general practice: Consultations, diagnosis, diagnostics and treatment choices

The aim of this study is to present diagnostic patterns, diagnostics used and antibiotic treatment in relation to guidelines in 3 repeated diagnosis-prescription studies conducted simultaneously in general practice in 5 Swedish counties, during 1 week in November 2000, 2002 and 2005. General practitioners (GPs) at the participating health centres were asked to complete a form for all patients with symptoms of an infectious disease. During the studied periods a total of 15,371 consultations was registered. Consultations with GPs diagnosed as respiratory tract infection (RTI), especially consultations for sore throat, decreased considerably between y 2000 and 2005. The percentage of patients allocated an RTI diagnosis and prescribed an antibiotic declined significantly from 54% to 49% and the decline was most pronounced among children. Penicillin V remained the dominant antibiotic prescribed throughout the study periods. For lower urinary tract infections there was a significant change in choice of prescribed antibiotics with an increase for pivmecillinam and nitrofurantoin and a decrease for trimethoprim, in accordance with recommendations. The results indicate a quite close adherence to current guidelines, with changes in the pattern of consultations as well as in the management of infectious diseases in general practice in Sweden.

Pharmacokinetic and Pharmacodynamic Parameters for Antimicrobial Effects of Cefotaxime and Amoxicillin in an In Vitro Kinetic Model

ABSTRACT An in vitro kinetic model was used to study the relation between pharmacokinetic and pharmacodynamic (PK-PD) parameters for antimicrobial effect, e.g., the time above MIC (T>MIC), maximum concentration in serum (Cmax), and area under the concentration-time curve (AUC). Streptococcus pyogenes and Escherichia coli were exposed to cefotaxime, and the activity of amoxicillin against four strains ofStreptococcus pneumoniae with different susceptibilities to penicillin was studied. The drug elimination rate varied so that the T>MIC ranged from 20 to 100% during 24 h, while the AUC and/or the initial concentration (Cmax) were kept constant. For S. pyogenes and E. coli, the maximal antimicrobial effect (Emax) at 24 h occurred when the antimicrobial concentration exceeded the MIC for 50 and 80% of the strains tested, respectively. The penicillin-susceptible pneumococci (MIC, 0.03 mg/liter) and the penicillin-intermediate strain (MIC, 0.25 mg/liter) showed maximal killing by amoxicillin at a T>MIC of 50%. For a strain for which the MIC was 2 mg/liter, Cmax needed to be increased to achieve the Emax. Under the condition that Cmax was 10 times the MIC,Emax was obtained at a T>MIC of 60%, indicating that Cmax, in addition to T>MIC, may be an important parameter for antimicrobial effect on moderately penicillin-resistant pneumococci. For the strain for which the MIC was 4 mg/liter, the reduction of bacteria varied from −0.4 to −3.6 log10 CFU/ml at a T>MIC of 100%, despite an initial antimicrobial concentration of 10 times the MIC. Our studies have shown that the in vitro kinetic model is a useful complement to animal models for studying the PK-PD relationship for antimicrobial effect of antibiotics.

Prevalence of faecal ESBL carriage in the community and in a hospital setting in a county of Southern Sweden.

The aim of this study was to investigate the prevalence of extended-spectrum beta-lactamase (ESBL)-producing bacteria in patients at various hospital wards and in a group of relatively healthy volunteers, in order to obtain greater knowledge on how common these bacterial strains are in hospital settings and in the general community. Participants (n = 427) were enrolled at a University Hospital and at Primary Health Care Units (PHCUs) in Sweden in 2008 and 2010. The participants provided rectal swabs, which were tested for the occurrence of ESBL-producing bacteria. Positive samples were analysed with polymerase chain reaction (PCR) methods for bacterial strain typing and ESBL phylogroups. In 2008, the prevalence was 2.1% (2/96) in PHCU subjects and 1.8% (2/113) in hospital patients. In 2010, the prevalence was 3.0% (3/100) in PHCU subjects and 6.8% (8/118) in hospital patients. The dominating phylogroups were CTX-M-1 and CTX-M-9. All ESBL-positive isolates were Escherichia coli. We found a higher prevalence of ESBL faecal carriage than expected, both in the hospital setting and in the PHCU group.

Antibiotics Differ in Their Tendency to Cause Infusion Phlebitis: A Prospective Observational Study

Intravenous administration of antibiotics is a known risk factor for infusion phlebitis. We have previously demonstrated differences in cell toxicity for 4 antibiotics. Clinical experience indicates that antibiotics differ in their tendency to cause phlebitis. The present study was done prospectively on 550 patients with 1386 peripheral venous catheters. The incidence of phlebitis was 18.5% with antibiotics and 8.8% without (odds ratio 2.34). Dicloxacillin (odds ratio 5.74) and erythromycin (odds ratio 5.33) had the greatest tendency to cause phlebitis in univariate, multivariate and Cox regression analyses. Benzylpenicillin, cefuroxime and cloxacillin were also associated with a greater risk of phlebitis, whereas ampicillin, imipenem/cilastatin, clindamycin, netilmicin and vancomycin were not. Other risk factors were the site of insertion and age 51-60 y. Medication with warfarin was found to be protective, but not with aspirin. Treatment with low molecular weight heparin reduced the risk of phlebitis, but the difference was not significant. With regard to when antibiotics were given, the day-specific risk increased between Days 1 and 2, but no further on subsequent days. The hypothesis that antibiotics differ in their tendency to cause phlebitis was confirmed.

Frequent Emergence of Resistance in Clostridium difficile during Treatment of C. difficile-Associated Diarrhea with Fusidic Acid

ABSTRACT Samples from patients with Clostridium difficile-associated diarrhea (CDAD) that were randomized to fusidic acid (n = 59) or metronidazole (n = 55) therapy for 7 days were cultured for Clostridium difficile in feces on days 1, 8 to 13, and 35 to 40. Of the patients who were culture positive only before treatment, 77% (36/47) were permanently cured (no treatment failure and no clinical recurrence), compared to 54% (22/41) of those with persistence of C. difficile at one or both follow-ups (P = 0.03). A similar association between bacterial persistence and a worse outcome of therapy was seen in both treatment groups. Resistance to fusidic acid was found in 1 of 88 pretherapy isolates available, plus in at least 1 subsequent isolate from 55% (11/20) of patients who remained culture-positive after fusidic acid therapy. In 10 of these 11 patients, the resistant follow-up isolate(s) belonged to the same PCR ribotype as the susceptible day 1 isolate, confirming frequent emergence of resistance to fusidic acid during treatment. Despite this, 5 of these 11 patients were permanently cured with fusidic acid, relative to 5 of 9 patients with susceptible C. difficile at follow-up (P = 1.0). None of the 36 PCR ribotypes of C. difficile identified was associated with any particular clinical outcome or emergence of fusidic acid resistance. In conclusion, culture positivity for C. difficile was common after both fusidic acid and metronidazole therapy and was associated with treatment failure or recurrence of CDAD. Development of resistance in C. difficile was frequent in patients given fusidic acid, but it was without apparent negative impact on therapeutic efficacy in the actual CDAD episode.