Thirteen years of antibiotic susceptibility surveillance of Pseudomonas aeruginosa from intensive care units and urology services in the Netherlands.

The purpose of this study was the evaluation of trends in the antimicrobial resistance of Pseudomonas aeruginosa from intensive care unit (ICU) patients and urology patients in the Netherlands. From 1998 to 2010, 1,927 consecutive P. aeruginosa isolates from ICU (n = 1,393) and urology service patients (n = 534) of 14 university and referral hospitals all over the Netherlands were collected and their susceptibility to relevant antibiotics was determined according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Over time, a significant upward trend in the resistance of P. aeruginosa strains collected from ICUs to piperacillin (1.2 % to 10.6 %, p = 0.0175), piperacillin-tazobactam (1.2 % to 12.1 %, p = 0.0008), ceftazidime (1.2 % to 7.8 %, p = 0.0064), cefepime (4.8 % to 6.4 %, p = 0.0166), imipenem (6 % to 19.1 %, p < 0.0001), meropenem (8.3 % to 17 %, p = 0.0022) and ciprofloxacin (13.1 % to 31.2 %, p = 0.0024) was observed, as was the prevalence of multi-resistance (1.2 % to 8.5 %, p = 0.0002). For P. aeruginosa isolates from the urology services, the resistance to imipenem increased (4.1 % to 7.8 %, p = 0.0006) and to ciprofloxacin it decreased (22.4 % to 18.8 %, p = 0.025). Like in other countries, in the Netherlands, an increase in multi-resistant Gram-negatives is observed, suggesting the presence and dissemination of several mechanisms of resistance. Our findings emphasise the importance of local surveillance for the setting up of local antibiotic guidelines and to support optimal empiric therapy. With the observed increase in multi-resistance, the direct testing of alternative antibiotics like polymyxins and fosfomycin is essential. Our data also illustrate the importance of adequate outbreak control measures.

A 12 year (1998-2009) antibiotic resistance surveillance of Klebsiella pneumoniae collected from intensive care and urology patients in 14 Dutch hospitals.

OBJECTIVES: We evaluated the changes in antibiotic resistance from 1998 to 2009 of Klebsiella pneumoniae isolated from the intensive care units (ICUs) and urology services of 14 Dutch hospitals and the consequences for empirical therapy. METHODS: Quantitative antibiotic susceptibility testing of K. pneumoniae was performed in a central laboratory using a microbroth dilution method. Breakpoints were as defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). The prevalence of extended-spectrum ß-lactamase (ESBL)- and carbapenemase-producing isolates was determined. RESULTS: A significant increase in resistance among ICU isolates was observed for ceftazidime (4.2%-10.8%), ciprofloxacin (5.8%-18.5%) and trimethoprim/sulfamethoxazole (11.9%-23.1%), and for cefuroxime (2.8%-7.9%) and trimethoprim/sulfamethoxazole (13.5%-27.8%) among urology isolates. Among ICU isolates the prevalence of ESBLs increased significantly from 2% to 8%. Carbapenemase production was not demonstrated. Among ICU isolates the prevalence of multidrug resistance increased and has been ≥12% since 2004. Among urology isolates multidrug resistance was highest in 2009 at 7.4%. Overall, resistance was significantly higher among ICU isolates. CONCLUSIONS: We observed an increase in resistance among ICU and urology isolates and an increased prevalence of ESBLs among ICU isolates. Carbapenemase production was not demonstrated. A regular update of empirical treatment protocols based on actual surveillance data is justified.

Population structure of Staphylococcus aureus strains isolated from intensive care unit patients in the netherlands over an 11-year period (1996 to 2006).

The genetic background and the presence of several virulence factors of Staphylococcus aureus isolates from intensive care unit (ICU) patients from 14 hospitals in The Netherlands isolated from 1996 until 2006 were investigated. In total, 936 methicillin-susceptible S. aureus (MSSA) and 7 methicillin-resistant S. aureus (MRSA) isolates were collected. The genetic background was determined by spa typing and multilocus sequence typing (MLST). The virulence determinants Panton-Valentine leukocidin (PVL), toxic shock syndrome toxin 1 (TSST-1), and collagen adhesion (CNA) were detected with real-time PCR assays. On the MRSA isolates, mobile resistance staphylococcal cassette chromosome mec (SCCmec) typing was performed. Among the MSSA isolates, 313 different spa types were observed. A genetic background common to MRSA clones, e.g., MLST clonal complex 1 (CC1), CC5, CC8, CC22, CC30, and CC45, was observed among 62% of the isolates. The remaining isolates were associated with MSSA-related MLST CCs. MLST CC1, CC25, and CC30 were continuously present, and other MLST CCs fluctuated over time. Two percent of the MSSA isolates harbored PVL, 21% had TSST-1, and 46% were positive for CNA. There were no changes in the prevalence of the virulence factors over time. Four MRSA isolates were typed as ST8-MRSA-IV (where ST is the MLST sequence type and IV is the SCCmec type), two were ST5-MRSA-II, and one was ST228-MRSA-I. All MRSA isolates were PVL, CNA, and TSST-1 negative except for the two ST5-MRSA-II isolates, which were TSST-1 positive. No changes in the S. aureus genetic background and the prevalence of the virulence factors PVL, CNA, and TSST-1 were observed in ICU patients in The Netherlands over time.

Flucloxacillin, still the empirical choice for putative Staphylococcus aureus infections in intensive care units in the Netherlands.

OBJECTIVES: To determine the usefulness of flucloxacillin as empirical therapy for putative Staphylococcus aureus infections in intensive care unit (ICU) patients in the Netherlands, the antibiotic resistance of S. aureus isolates from ICUs over a 13 year period was investigated. METHODS: From 1996 to 2008, 1146 consecutive S. aureus isolates from ICU patients in 14 large referral hospitals were collected. The susceptibility to relevant antibiotics was determined by microbroth dilution according to CLSI guidelines. RESULTS: Resistance to flucloxacillin was only found in 12 isolates (1%). The resistance to clarithromycin, ciprofloxacin and moxifloxacin showed a significant trend over time, from 4.2% to 10.3%, from 1.0% to approximately 10% and from 0.0% to approximately 5.0%, respectively (P < 0.05). The resistance to penicillin, clindamycin and doxycycline increased over time, from 74% to 75%, from approximately 3.0% in 1996 to 3.2% in 2008 and from 2.2% in 1996 to 8.2% in 2008, respectively (P > 0.05). Resistance to cephalosporins, carbapenems, rifampicin and gentamicin was sporadically observed. No resistance was found to vancomycin, teicoplanin and linezolid. CONCLUSIONS: The empirical choice of flucloxacillin in the case of putative S. aureus infections in patients admitted to ICUs in the Netherlands is still justified.

Antimicrobial resistance in Escherichia coli and Pseudomonas aeruginosa from Intensive Care Units in The Netherlands, 1998-2005.

In 1998, a nationwide surveillance of antibiotic resistance among Escherichia coli and Pseudomonas aeruginosa isolates of patients from 14 Intensive Care Units in The Netherlands was initiated. Minimal inhibitory concentrations (MICs) of broad-spectrum penicillins with and without beta-lactamase inhibitors, cephalosporins, aminoglycosides and fluoroquinolones were determined by a broth microdilution method. An increase in percentages of resistance of E. coli and P. aeruginosa to most antibiotics tested was observed, but rates were still lower than those described in other countries. For E. coli, resistance to amoxicillin was fairly stable at 44% until 2004 and increased to 56% (P=0.01) in 2005. Similarly, piperacillin had a resistance rate of ca. 11% until 2004, which then increased to 38% in 2005 (P<0.001). The MIC distributions of piperacillin and piperacillin/tazobactam for P. aeruginosa were almost identical, as were the resistance rates (4-14%). Resistance to ciprofloxacin nearly doubled in 2005 compared with previous years. Changes in resistance to the antibiotics tested were confirmed by trend analysis. Together with infection control measures, antibiotic resistance surveillance is an important tool to control the antibiotic resistance problem.

Antimicrobial resistance in Gram-negative bacteria from Intensive Care Units and Urology Services. A nationwide study in The Netherlands 1995-2000.

A nationwide 6-year surveillance of resistance in Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa from clinical specimens of patients from ten Intensive Care Units and ten Urology Services was started in 1995. MICs of amoxycillin, amoxycillin/clavulanate, trimethoprim, cotrimoxazole, norfloxacin, ciprofloxacin, cefaclor, ceftazidime, imipenem and gentamicin were determined by broth microdilution. Intensive Care Units had higher resistance levels of amoxycillin/clavulanate, cefaclor and ceftazidime (P<0.005) and lower resistance levels of nitrofurantoin, trimethoprim, cotrimoxazole and quinolones (P<0.01) than Urology Services. Changes in MIC distributions in time and development of resistant clusters were observed for nitrofurantoin (E. coli), amoxycillin (E. coli, P. mirabilis), amoxycillin/clavulanate (E. coli) and for quinolones (E. coli). The overall resistance level of ceftazidime and gentamicin was <5%, but this fluctuated with the appearance and disappearance of resistant clones in some Intensive Care Units. Quinolone resistance among P. aeruginosa from Intensive Care Units fluctuated between 7 and 14%.

[Nutrition and health--infections caused by food]. / Voeding en gezondheid--infecties door voedsel.

The annual incidence of food-borne infections in the Netherlands is estimated to be 250,000 or more; registration, however, is lacking. Meat, poultry, milk and eggs are contaminated primarily by intestinal animal commensals (Salmonella, Campylobacter, E. coli O157:H7, Yersinia enterocolitica) or secondarily by animals, humans and the environment during processing (typhoid fever, Shigella, Listeria, Clostridium, hepatitis A virus, Norwalk virus, parasites). The guidelines for the prevention of contamination are insufficient. Intensity of production and the economic importance of fast, large-scale production are given priority over food safety. Information fails to reach the consumer.

[Antibiotic resistance: recommendations from the Advisory Council for Health Research]. / Antibioticaresistentie; een advies van de Raad voor Gezondheidsonderzoek.

The Advisory Council for Health Research (RGO) advised the Dutch Minister of Health on research into the epidemiology, prevention and research of antibiotic resistance in the Netherlands. Good antimicrobial practice, insight into antibiotic use, implementation of measures to prevent development of resistance and fundamental research on resistance should be promoted. It was concluded that there is very little extramural surveillance and that only a few existing intramural surveillance programmes appear useful for long-term monitoring, inclusion into international databases and comparison purposes. The initiatives taken by the Working Party on Antibiotic Policy (SWAB) and the National Institute of Public Health and the Environment (RIVM), including the development of a standard for susceptibility testing and the coordination of surveillance studies according to international standards, should be supported and continued. The RGO committee is impressed by central and integrated national surveillance programmes such as those in Denmark or Finland. This approach however seems not necessary for good medical practice and not currently feasible. Priority should now be given to specific projects which focus on specific resistance problems among well-defined patient groups, and on indicator-organisms and indicator-antibiotics.

The impact of nontuberculous mycobacteria on management of presumed pulmonary tuberculosis.

BACKGROUND: The presence of nontuberculous mycobacteria (NTM) in sputum or bronchial washings may cause diagnostic problems which affect clinical management. PATIENTS AND METHODS: In a retrospective analysis of 135 patients in a Dutch tuberculosis center, patients with NTM isolates were thoroughly investigated. Colonization or contamination by NTM was differentiated from true lung disease. RESULTS: 25 HIV-seronegative and two HIV-seropositive patients with NTM were identified. NTM were a likely cause of disease in only 14 (52%) patients. In 15 (55%), their presence led to preliminary diagnosis and treatment of tuberculosis. Unnecessary or inappropriate treatment was instituted in 17 (63%) patients with NTM. In two patients, detection of NTM in sputum also led to delay in diagnosing malignant disease. CONCLUSION: In this series, NTM in sputum or bronchial washings poorly reflected disease and often led to diagnostic and therapeutic errors. Although it is common knowledge that the presence of NTM should be considered in smear-positive patients, this apparently is a diagnostic pitfall in clinical practice. Reliable DNA-based techniques and better communication between physicians and microbiologists may improve management of suspected mycobacterial infections.

Molecular analysis of Tn1546-like elements in vancomycin-resistant enterococci isolated from patients in Europe shows geographic transposon type clustering.

Resistance mechanism relatedness was studied in 18 clinical, European vanA vancomycin-resistant enterococci. Molecular analysis revealed 10 Tn1546-like elements, suggesting two evolutionary lineages. Lineage I dominated the European mainland, and lineage II dominated the United Kingdom and Israel. Geographic clustering reflected different types of meat consumption between countries, since each lineage is associated with colonization of different animals.

SHV-14, a novel beta-lactamase variant in Klebsiella pneumoniae isolates from Nijmegen, The Netherlands.

Four ceftazidime-resistant isolates of a Klebsiella pneumoniae strain were collected from intensive care unit patients in Nijmegen, The Netherlands. These isolates had TEM-29 and SHV-14 beta-lactamases. SHV-14 is a novel variant, with two substitutions compared with the sequence of SHV-1: Ile8Phe and Arg43Ser. Its gene also had a silent C-->T mutation at nucleotide 481. The SHV-14 enzyme had slightly higher V(max) rates than SHV-1 for oxyimino-aminothiazolyl cephalosporins, but this activity was insufficient for the enzyme to count as an extended-spectrum beta-lactamase.

Ciprofloxacin v placebo for treatment of Yersinia enterocolitica triggered reactive arthritis.

Patients with yersinia triggered reactive arthritis were double blind randomly allocated to receive treatment with ciprofloxacin 500 mg twice daily orally or placebo during three months. The diagnosis was made by serology (specific IgA and IgG antibodies to yersinia outer membrane proteins (yops)), positive culture, and/or demonstration of Yersinia enterocolitica antigen in colon biopsy specimens. Patients were evaluated monthly during and after treatment up to 12 months. Of 18 patients enrolled, all could be evaluated for safety, 16 for efficacy. There was a tendency towards faster remission and relief of pain in those receiving ciprofloxacin. Y enterocolitica was eliminated from the gut associated lymphoid tissue in six of seven patients receiving ciprofloxacin compared with none of nine patients receiving placebo. Patients receiving placebo had more and prolonged circulating IgA antibodies against yops than patients treated with ciprofloxacin.

Comparative in vitro activity of moxifloxacin against Gram-positive clinical isolates.

The in vitro activity of moxifloxacin was compared with that of 15 antibacterial agents against 513 Gram-positive microorganisms. The MIC(90) (mg/L) of moxifloxacin was 0.06 for quinolone-susceptible Staphylococcus aureus and Staphylococcus epidermidis, 0.12 for Streptococcus pyogenes and Streptococcus agalactiae; 0.25 for Streptococcus pneumoniae, Streptococcus mitis, Streptococcus bovis, Streptococcus anginosus and Actinomyces pyogenes; 0.5 for Streptococcus sanguis and Listeria monocytogenes, 2 for Corynebacterium jekeium and Bifidobacterium bivius. Over 50% of Enterococcus faecalis, Enterococcus faecium, quinolone-resistant staphylococci, Nocardia steroides and Clostridium difficile were susceptible to 2 mg/L moxifloxacin. Moxifloxacin and trovafloxacin demonstrated comparably high activity towards Gram-positive cocci; moxifloxacin and clinafloxacin were most active against Gram-positive bacilli.

Prevalence of vancomycin-resistant enterococci in Europe.

The aim of the present study was to determine the prevalence of vancomycin-resistant enterococci (VRE) in Europe. Overall, 49 laboratories in 27 countries collected 4,208 clinical isolates of enterococci. Species identification, susceptibility testing, and van gene determination by polymerase chain reaction were performed in a central laboratory. Overall, 18 vanA and 5 vanB isolates of VRE were found. The prevalence of vanA VRE was highest in the UK (2.7%), while the prevalence of vanB VRE was highest in Slovenia (2%). Most vanA and vanB VRE were identified as Enterococcus faecium. Most VRE isolates originated from the patient's urogenital tract, skin, or digestive tract. VRE were equally distributed among clinical departments, with no clear preponderance in any single patient group. A total of 71 isolates containing the vanC gene were identified. The prevalence of vanC VRE was highest in Latvia and Turkey, where rates were 14.3 and 11.7%, respectively. Two-thirds of these isolates were identified as Enterococcus gallinarum and one-third as Enterococcus casseliflavus; the majority of these isolates were cultured from feces. Almost all isolates were obtained from hospitalized patients, mostly children. The highest prevalence of high-level gentamicin-resistant enterococci was seen in Turkey and Greece. In general, the distribution of this resistance type seemed unrelated to the occurrence of VRE. The prevalence of vanA/ vanB VRE in Europe is still low; the majority of the VRE isolates exhibit the vanC genotype and colonize the gastrointestinal tract of hospitalized children.

Antimicrobial susceptibility patterns of enterococci causing infections in Europe. The European VRE Study Group.

In vitro susceptibilities of 4,208 enterococci (83% Enterococcus faecalis isolates, 13.6% Enterococcus faecium isolates, and 3.4% isolates of other species) from patients in 27 European countries towards 16 antibiotics were determined. High-level resistance to gentamicin varied by country (range, 1 to 49%; mean, 22.6% +/- 12. 3%) and per species (19.7% E. faecalis isolates, 13.6% E. faecium isolates, 3.4% by other species). Vancomycin resistance was detected in 0.06% E. faecalis, 3.8% E. faecium, and 19.1% isolates of other species. All enterococci were susceptible to LY 333328 and everninomicin, and 25% of E. faecalis isolates and 85% of other enterococci were susceptible to quinupristin-dalfopristin. The MIC of moxifloxacin and trovafloxacin for ciprofloxacin-susceptible E. faecalis at which 90% of the isolates were inhibited was 0.25 to 0.5 microg/ml.

[Growth promoting antimicrobials]. / Antimicrobiële groeibevorderaars.

The committee 'Growth promoting antimicrobials' of the Health Council of the Netherlands in 1998 advised immediate prohibition of all growth promoting antimicrobials related to human drugs and decrease of use of other growth promoting antimicrobials during the next three years in Europe. It is clear that frequent use of antibiotics is associated with development of resistance by selection in animals (and man), but it is not proven that this is an explanation of resistance in the human community. We know only little about the mechanisms and conditions of transfer of bacteria to man. Other questions raised are: what about the resulting possible increase of therapeutic application of antibiotics in animals, how to handle the increase of dung, nitrogen and phosphate in the environment and how farmers can survive with a decrease in income, sometimes by as much as 50%? Although many will feel sympathy for the report and its recommendations, implementing them will be difficult and possibly premature.

[Therapeutic options for HIV infection should lead to increased utilization of HIV tests]. / Therapeutische mogelijkheden bij HIV-infectie nopen tot verruiming van het HIV-testbeleid.

Owing to the recent advances in drug therapy for HIV infected patients, HIV infection is no longer an untreatable condition. The Health Council of the Netherlands therefore considers the advantages of knowing a person's HIV status to outweigh the disadvantages, especially for pregnant women. The restrictive policy with respect to HIV testing should be discontinued.

Occurrence of extended-spectrum betalactamases (ESBL) in Dutch hospitals.

The prevalence of ESBL was determined among isolates of Escherichia coli (n = 571) and Klebsiella spp. (n = 196) collected during a 1-week study period in 8 university and 3 large regional laboratories all over the Netherlands. 18 isolates were positive for at least one of the screening tests used, i.e., VITEK-ESBL, E-test ESBL and MIC ratio of ceftazidime/ceftazidime-clavulanic acid, cefotaxime/cefotaxime-clavulanic acid. In 5 of these 18 putative ESBLs no betalactamase production was detectable. A TEM type was found in three E. coli and two Klebsiella spp. An SHV type was present in five Klebsiella spp. In one E. coli and one Klebsiella pneumoniae both enzymes were present. In one Klebsiella oxytoca neither of the two enzymes was present. Using PCR for both ESBL TEM and ESBL SHV, an SHV ESBL was found in one E. coli and four Klebsiella isolates. The mutations at position 238 and 240 were already described. In one E. coli isolate a TEM ESBL was found with three mutations, at position 21, 164 and 265. These mutations were already described in other ESBLs but not in this combination suggesting a new TEM ESBL. The overall prevalence of ESBL producing E. coli and Klebsiella spp. was less than 1% (6 out of 767).

Yersinia enterocolitica and the chronic fatigue syndrome.

OBJECTIVES: To investigate the potential role of Yersinia enterocolitica in patients with chronic fatigue syndrome (CFS). METHODS: An immunoblot technique was used to detect antibodies to various Yersinia outer membrane proteins (YOPs) in serum samples from 88 patients with CFS and 77 healthy neighbourhood controls, matched for gender and age. RESULTS: The prevalence of IgG and IgA antibodies to various Yersinia outer membrane proteins (YOPs) did not differ between patients with CFS and healthy controls. Twenty-four patients (27%) and nineteen controls (25%) had IgG antibodies to one or more YOPs. Four patients and two controls had both serum IgG and IgA antibodies to at least two different YOPs, compatible with a recent or persistent infection. Although all patients with positive IgG and IgA reactions to two or more YOPs had symptoms that could point to persistent Yersinia infection, these symptoms were also found frequently in patients without antibodies to YOPs. CONCLUSIONS: We conclude that Y. enterocolitica is unlikely to play a major role in the aetiology of CFS.