Nitrofurantoin for the treatment of uncomplicated urinary tract infection in female patients: the impact of dosing regimen, age, and renal function on drug exposure.

PURPOSE: The aim of this study is to determine nitrofurantoin exposure in female patients with different age and renal function with complaints of an uncomplicated UTI. Also the nitrofurantoin exposure in relation to the dosage regimen will be studied. METHODS: Eight general practitioners (GP) participated in the study and included 38 patients with symptoms of an uncomplicated UTI, treated either with a dose of 50 mg q6h or 100 mg q12h, upon the discretion of the GP. Nitrofurantoin exposure was quantified in the patient's 24-h urine samples by UHPLC-UV and the area under the curve was calculated. RESULTS: The 38 patients provided a range of 2-17 urine samples. The urine nitrofurantoin exposure was 1028 mg h/L for the patients receiving 50 mg q6h and 1036 mg h/L for those treated with 100 mg q12h (p = 0.97) and was not affected by age and eGFR (p = 0.64 and p = 0.34, respectively). CONCLUSION: The data obtained do not support the discouragement of nitrofurantoin use in the elderly and in patients with impaired renal function. Since only a small number of patients were included, a larger study with more patients is warranted to evaluate nitrofurantoin exposure and adverse effects.

Adherence to and usefulness of the national treatment guideline for urinary tract infections (UTI) in a risk area.

BACKGROUND: To optimize antibiotic treatment and decrease antibiotic resistance, national treatment guidelines are available for urinary tract infections (UTIs) in general practice. The usefulness of these guidelines in risk areas for antimicrobial resistance such as cross border regions or areas with dense agriculture, is unknown. METHODS: Midstream urine samples from women with symptoms of acute UTI visiting general practitioners (GPs) in the Westland area, a dense agriculture area, were microbiologically analysed, and patient characteristics, symptoms, previous and present antibiotic treatment were collected. The National Nivel data were used as reference for antibiotic resistance. RESULTS: Of 310 women with symptoms of uncomplicated UTI, 247 (80%) had a culture proven E. coli UTI. Empirical antibiotic therapy was prescribed to 148 patients (48%) in total; in 7% of women with a negative and 52% with a positive urine culture. Having more than one symptom was associated with the prescription of antibiotics; travel history or previous antibiotic use for UTI were not. The isolated uropathogens were susceptible to the empiric antibiotic therapy in 98% of patients. Resistance to co-amoxiclav was higher (22%) than reported in the national data of 2004 (12%), 2009 (13%) and 2014 (9%), as was the prevalence of extended spectrum ß-lactamase (ESBL): 3.4% in our study versus 0.1%, 1% and 2.2% in the national data respectively. CONCLUSION: The presence of environmental and socio-demographic risk factors for antibiotic resistance did not influence the empiric choice nor susceptibility for antibiotics advised by the national guidelines in women with uncomplicated UTI.

Differentiation between Streptococcus pneumoniae and other viridans group streptococci by matrix-assisted laser desorption/ionization time of flight mass spectrometry.

OBJECTIVES: Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is becoming the method of choice for bacterial identification. However, correct identification by MALDI-TOF of closely related microorganisms such as viridans streptococci is still cumbersome, especially in the identification of S. pneumoniae. By making use of additional spectra peaks for S. pneumoniae and other viridans group streptococci (VGS). We re-identified viridans streptococci that had been identified and characterized by molecular and phenotypic techniques by MALDI-TOF. METHODS: VGS isolates (n = 579), 496 S. pneumoniae and 83 non-S. pneumoniae were analysed using MALDI-TOF MS and the sensitivity and specificity of MALDI-TOF MS was assessed. Hereafter, mass spectra analysis was performed. Presumptive identification of proteins represented by discriminatory peaks was performed by molecular weight matching and the corresponding nucleotides sequences against different protein databases. RESULTS: Using the Bruker reference library, 495 of 496 S. pneumoniae isolates were identified as S. pneumoniae and one isolate was identified as non-S. pneumoniae. Of the 83 non-S. pneumoniae isolates, 37 were correctly identified as non-S. pneumoniae, and 46 isolates as S. pneumoniae. The sensitivity of the MALDI-TOF MS was 99.8% (95% confidence interval (CI) 98.9-100) and the specificity was 44.6% (95% CI 33.7-55.9). Eight spectra peaks were mostly present in one category (S. pneumoniae or other VGS) and absent in the other category and inversely. Two spectra peaks of these (m/z 3420 and 3436) were selected by logistic regression to generate three identification profiles. These profiles could differentiate between S. pneumoniae and other VGS with high sensitivity and specificity (99.4% and 98.8%, respectively). CONCLUSIONS: Spectral peaks analysis based identification is a powerful tool to differentiate S. pneumoniae from other VGS species with high specificity and sensitivity and is a useful method for pneumococcal identification in carriage studies. More research is needed to further confirm our findings. Extrapolation of these results to clinical strains need to be deeply investigated.

Antibiotic resistance of Escherichia coli isolated from uncomplicated UTI in general practice patients over a 10-year period.

Recommendations of first choice antibiotic therapy need to be based on actual antibiotic susceptibility data. We determined the antibiotic susceptibility of E. coli in uncomplicated UTI among women and compared the results with 2004 and 2009. In 30 sentinel general practitioner practices of Nivel Primary Care database, urine samples were collected from women with symptoms of uncomplicated UTI. Patient characteristics, E. coli susceptibility, and ESBL production were analyzed. Six hundred eighty-nine urine samples were collected; E. coli was the most isolated uropathogen (83%). Antibiotic susceptibility was stable over time except for ciprofloxacin (96% in 2004, 97% in 2009, and 94% in 2014; P < 0.05). The susceptibility to co-amoxiclav was 88%, 87%, and 92% in 2004, 2009, and 2014, respectively. The prevalence of ESBL-producing E. coli increased from 0.1% in 2004 to 2.2% in 2014 (P < 0.05). Regional differences in antibiotic susceptibility for co-trimoxazole were found being the highest in the west (88%) and the lowest in the north (72%, P = 0.021). Ciprofloxacin susceptibility was related to antibiotic use in the past 3 months (97% no use versus 90% use, P = 0.002) and age > 70 years (P = 0.005). In 2014, prescription of fosfomycin increased compared to 2009 (14.3% versus 5.6%) at the expense of co-amoxiclav, co-trimoxazole, and fluoroquinolones (P < 0.05). The susceptibility percentages to most antimicrobial agents tested were stable over 10 years' period although the prevalence of E. coli and ESBLs significantly increased. Performance of a survey with regular intervals is warranted.

Urine cultures in a long-term care facility (LTCF): time for improvement.

BACKGROUND: Urinary tract infections (UTIs) are the most prevalent infections in long-term care facilities (LTCFs). Numerous studies have described the problem of inadequate UTI diagnosis and treatment. We assessed the role of urine cultures in the diagnosis and treatment of UTIs in a LTCF. METHODS: In a 370-bed non-academic LTCF a retrospective assessment of antibiotic (AB) prescriptions for UTIs and urine cultures was performed from July 2014 to January 2016. The reasons why physicians, including 11 nursing home physicians and 2 junior doctors, ordered urine cultures were recorded using questionnaires. RESULTS: During the study period, 378 residents were prescribed 1672 AB courses; 803 were for UTIs. One hundred and fifty-five urine cultures were obtained from 135 residents; 66 of these cultures were performed on the same day as ABs were prescribed (8% of all prescriptions for UTI), while 89 were not. There was a discrepancy between the actions that seemed logical based on the culture results and the actions that were actually taken in 75% of the cases. In these cases, initial AB treatment was not adjusted when the isolated microorganism was resistant to the AB prescribed, the urine culture was positive and no ABs had previously been administered, or ABs were prescribed and no microorganism was isolated. The most frequent reason for ordering a urine culture was to confirm the diagnosis of a UTI. CONCLUSION: In the majority of patients, AB therapy was not adjusted when the urine culture results suggested it may be appropriate. The physicians were erroneously convinced that UTIs could be diagnosed by a positive urine culture.

Electronic nose analysis of exhaled breath to diagnose ventilator-associated pneumonia.

BACKGROUND: Exhaled breath analysis is an emerging technology in respiratory disease and infection. Electronic nose devices (e-nose) are small and portable with a potential for point of care application. Ventilator-associated pneumonia (VAP) is a common nosocomial infection occurring in the intensive care unit (ICU). The current best diagnostic approach is based on clinical criteria combined with bronchoalveolar lavage (BAL) and subsequent bacterial culture analysis. BAL is invasive, laborious and time consuming. Exhaled breath analysis by e-nose is non-invasive, easy to perform and could reduce diagnostic time. Aim of this study was to explore whether an e-nose can be used as a non-invasive in vivo diagnostic tool for VAP. METHODS: Seventy-two patients met the clinical diagnostic criteria of VAP and underwent BAL. In thirty-three patients BAL analysis confirmed the diagnosis of VAP [BAL+(VAP+)], in thirty-nine patients the diagnosis was rejected [BAL-]. Before BAL was performed, exhaled breath was sampled from the expiratory limb of the ventilator into sterile Tedlar bags and subsequently analysed by an e-nose with metal oxide sensors (DiagNose, C-it, Zutphen, The Netherlands). From further fifty-three patients without clinical suspicion of VAP or signs of respiratory disease exhaled breath was collected to serve as a control group [control(VAP-]). The e-nose data from exhaled breath were analysed using logistic regression. RESULTS: The ROC curve comparing [BAL+(VAP+)] and [control(VAP-)] patients had an area under the curve (AUC) of 0.82 (95% CI 0.73-0.9). The sensitivity was 88% with a specificity of 66%. The comparison of [BAL+(VAP+)] and [BAL-] patients revealed an AUC of 0.69; 95% CI 0.57-0.81) with a sensitivity of 76% with a specificity of 56%. CONCLUSION: E-nose lacked sensitivity and specificity in the diagnosis of VAP in the present study for current clinical application. Further investigation into this field is warranted to explore the diagnostic possibilities of this promising new technique.

Cost analysis of one of the first outpatient wound clinics in the Netherlands.

OBJECTIVE: To perform, from an insurance perspective, a cost analysis of one of the outpatient community wound care clinics in the Netherlands, the Knowledge Centre in Wound Care (KCWC) at Venray. METHOD: This study involved a cost analysis based on an observational cohort study with a one-year pre-admission and a one-year post-admission comparison of costs. Patients were included when they first consulted the outpatient wound care clinic. Participants were all insured by the same health insurance company, Coöperatie Volksgezondheidszorg (VGZ). A standard six-step procedure for performing cost studies was used to calculate the costs. Given the skewed cost data, non-parametric bootstrapping was used to test for statistical differences. RESULTS: There were 172 patients included in this study. The difference in costs related to wound care between the year before and the year after initial admission to the wound clinic amounted to an average reduction of €2621 (£1873) per patient in the base case analysis. The categories 'general practitioner', 'hospital care', 'mental health care' and 'transport' scored lower, indicating lower costs, in the year after admission to the wound clinic. CONCLUSION: In this study, only the reimbursement data of patients of one health insurance company, and specifically only those made under the 2006 Dutch Health Insurance Act, were available. Because of the observational design, definitive conclusions cannot be made regarding a demonstrated reduction of costs in the year post admission. Nevertheless, this study is a first attempt of a cost analysis of an equipped outpatient wound clinic as an innovative way of responding to the increasing number of chronic wounds in the Netherlands. The calculations show that savings in wound care are possible. DECLARATION OF INTEREST: A possible conflict of interest should be mentioned. First author AALM Rondas, PhD student at Maastricht University, is working at the KCWC wound clinic at Venray in the Netherlands as a physician. However, the research data were provided externally by Coöperatie Volksgezondheidszorg (VGZ) and checked by the academic co-authors, none of whom have a conflict of interest. The authors have no financial or commercial interest to declare.

Impact of same-day antibiotic susceptibility testing on time to appropriate antibiotic treatment of patients with bacteraemia: a randomised controlled trial.

Inadequate therapy in bloodstream infections is suggested to be associated with higher mortality. We evaluated the reduction in inappropriate antibiotic therapy using rapid identification and antibiotic susceptibility testing (FAST) compared to standard of care (SOC) testing in patients with bloodstream infections. The FAST method used polymerase chain reaction (PCR) for identification and to detect growth in the presence or absence of antibiotics after only 6 h. For SOC testing, the BD Phoenix system was used. Patients with blood cultures growing Staphylococcus, Streptococcus or Enterococcus species or Gram-negative rods were randomised for FAST or SOC tests. A total of 129 patients were randomised for FAST and 121 patients for the SOC group. At the time SOC results became available, 78 patients in the FAST group could have been switched to more appropriate therapy. Although FAST results were highly accurate (agreement with SOC was 94%), they were only implemented in a minority (16) of patients. However, significantly fewer patients in the FAST group used inappropriate therapy at the time of SOC results (p = 0.025). The time to results in the FAST group was reduced by 15.6 h (p < 0.001). In the patients switched after FAST, this was done after a mean of 42.3 h compared to 61.4 h in those switched after SOC tests (p < 0.001). In bacteraemic patients, FAST resulted in significantly more patients using appropriate antibiotic therapy at the time SOC results were available and 15.6 h earlier than SOC tests. However, the implementation of FAST results was not optimal and no benefit on clinical outcome was shown.

Identification of microorganisms based on headspace analysis of volatile organic compounds by gas chromatography-mass spectrometry.

The identification of specific volatile organic compounds (VOCs) produced by microorganisms may assist in developing a fast and accurate methodology for the determination of pulmonary bacterial infections in exhaled air. As a first step, pulmonary bacteria were cultured and their headspace analyzed for the total amount of excreted VOCs to select those compounds which are exclusively associated with specific microorganisms. Development of a rapid, noninvasive methodology for identification of bacterial species may improve diagnostics and antibiotic therapy, ultimately leading to controlling the antibiotic resistance problem. Two hundred bacterial headspace samples from four different microorganisms (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumoniae) were analyzed by gas chromatography-mass spectrometry to detect a wide array of VOCs. Statistical analysis of these volatiles enabled the characterization of specific VOC profiles indicative for each microorganism. Differences in VOC abundance between the bacterial types were determined using ANalysis of VAriance-principal component analysis (ANOVA-PCA). These differences were visualized with PCA. Cross validation was applied to validate the results. We identified a large number of different compounds in the various headspaces, thus demonstrating a highly significant difference in VOC occurrence of bacterial cultures compared to the medium and between the cultures themselves. Additionally, a separation between a methicillin-resistant and a methicillin-sensitive isolate of S. aureus could be made due to significant differences between compounds. ANOVA-PCA analysis showed that 25 VOCs were differently profiled across the various microorganisms, whereas a PCA score plot enabled the visualization of these clear differences between the bacterial types. We demonstrated that identification of the studied microorganisms, including an antibiotic susceptible and resistant S. aureus substrain, is possible based on a selected number of compounds measured in the headspace of these cultures. These in vitro results may translate into a breath analysis approach that has the potential to be used as a diagnostic tool in medical microbiology.

Adequacy of an evidence-based treatment guideline for complicated urinary tract infections in the Netherlands and the effectiveness of guideline adherence.

Guideline recommendations on empirical antibiotic treatment are based on the literature, expert opinion, expected pathogens and resistance data, but their adequacy in the real-life setting is often unknown. We investigated the adequacy of the Dutch evidence-based guideline-recommended treatment options for patients with complicated urinary tract infections (UTIs) 2 years after guideline publication and, additionally, the adequacy of actually prescribed empirical therapy for patients treated with guideline-adherent versus non-guideline-adherent therapy. A retrospective, observational multicentre study in the Netherlands included 810 patients with a complicated UTI without special conditions and 174 with a urinary catheter. The susceptibility patterns of cultured uropathogens were compared with guideline-recommended treatment options, which included specific recommendations for patients with a catheter, and with actually prescribed empirical therapy. We considered inadequate coverage rates below 10% as acceptable. Of the recommended regimens for patients with a UTI without other conditions, only the guideline-recommended combination of amoxicillin-gentamicin was acceptable (inadequate coverage rate 6%). For patients with a catheter, inadequate coverage rates of recommended regimens ranged from 3 to 24%. In patients with a UTI without other conditions, actually prescribed guideline-adherent therapy resulted in less broad-spectrum but not in less adequate therapy; in patients with a catheter, actually prescribed guideline-adherent therapy resulted in a higher coverage rate than those prescribed non-guideline-adherent therapy. Due to the continuously changing resistance rates and differences between the epidemiologies of uropathogens assumed in the guideline and those in real life, regular real-life assessments of recommended treatment options are necessary. Guideline adherence seems to be effective for increasing coverage rates without prescribing unnecessarily broad regimens.

Antibiotic resistance, population structure and spread of Staphylococcus aureus in nursing homes in the Euregion Meuse-Rhine.

To determine the spread of Staphylococcus aureus within and between nursing home (NH) residents in the Euregion Meuse-Rhine, a cross-border region of the Netherlands and Germany, we investigated the prevalence of antibiotic resistance, genetic background and population structure of both methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates. A total of 245 S. aureus isolates were collected from NH residents. Susceptibility testing was performed with microbroth dilution. The genetic background was determined using spa typing, SCCmec typing, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Differences in the prevalence of resistance between the German and Dutch MSSA isolates were observed for the macrolides (15 % vs. 2 %, p = 0.003), clindamycin (15 % vs. 0 %, p = 0.003) and ciprofloxacin (34 % vs. 25 %). The macrolide and ciprofloxacin resistance varied between the NHs, while trimethoprim-sulfamethoxazole resistance was low in all residents. The MRSA prevalence was 3.5 % and <1 % among the German and Dutch NH residents, respectively (p = 0.005). The German MRSAs, isolated in 7 out of 10 NHs, belonged to ST22-MRSA-IV or ST225-MRSA-II. spa clonal complexes (spa-CCs) 015 and 002 were prevalent among the German MSSA isolates and spa-CCs 024 and 1716 were prevalent among the Dutch MSSA isolates. The antibiotic resistance of MSSA and the MRSA prevalence were significantly higher among the German NH residents. The spread of two MRSA clones was observed within and between the German NHs, but not between the Dutch and German NHs. Differences in the prevalence of resistance and the prevalence of MRSA between NHs on both sides of the border warrant the continuation of surveillance at a local level.

Is living in a border region a risk for a high prevalence of resistance?

This study assessed the antimicrobial resistance and population structure of Staphylococcus aureus isolated from general practice (GP) patients and nursing home (NH) residents in the province of Limburg (near the border with Germany and Belgium) in comparison with those obtained in the remaining provinces of the Netherlands. A total of 617 and 418 S. aureus isolates were isolated from 2,691 to 1,351 nasal swabs from GP patients and NH residents, respectively. Quantitative antibiotic susceptibility testing was performed using a microbroth dilution method. Putative methicillin-resistant S. aureus (MRSA) isolates were tested for the presence of the mecA gene and spa typing was performed on all S. aureus isolates. No significant differences in the prevalence of resistance were found between the two groups of GP isolates, but the isolates from the NH residents showed a lower resistance for trimethoprim-sulfamethoxazole (p = 0.003) in Limburg province compared with the remaining provinces in the Netherlands. Among the isolates from NH residents in Limburg province, the prevalence of spa-CC 084 was higher (p = 0.003) and that of spa-CC 002 was lower (p = 0.01) compared with isolates from NHs in the remaining provinces of the Netherlands. We observed no differences in resistance and population structure between S. aureus isolates from GP patients in Limburg and the remaining provinces of the Netherlands, and only a few differences were observed between the NH populations. There was no higher prevalence of resistance among the GP and NH isolates from Limburg compared with the remaining provinces.

Prevalence and spread of multidrug resistant Escherichia coli isolates among nursing home residents in the southern part of The Netherlands.

OBJECTIVES: Empiric antibiotic treatment should be based on recent surveillance data. Therefore, we conducted a surveillance of (multidrug) resistance of Escherichia coli and antibiotic use among Dutch nursing home (NH) residents. Pulsed-field gel electrophoresis and multilocus sequence typing were used to describe the spread of multidrug-resistant strains. DESIGN: Observational study. SETTING: Five NHs in the southern part of The Netherlands. PARTICIPANTS: A total of 337 NH residents from both somatic and psychogeriatric wards. MEASUREMENTS: The prevalence and spread of antibiotic resistance and multidrug resistant E. coli isolates collected from urine samples and antibiotic use among the NH residents were investigated. RESULTS: A total of 208 E. coli isolates were collected from 308 urine samples. Resistance to amoxicillin-clavulanic acid was 23% and resistance to ciprofloxacin was 16%. Resistance to trimethoprim-sulfamethoxazole was 19%, whereas nitrofurantoin resistance was less than 1%. Multidrug resistance was observed in 28 of the 208 isolates (13%). Several isolates showed a similar pulsed-field gel electrophoresis pulsotype and multilocus sequence typing type. Sequence type (ST) 131 was the most prevalent (48%) and was demonstrated in all NHs and with four different pulsotypes. Consumption of antibiotics for systemic use was 64.4 defined daily dose (DDD)/1000 residents/day. Amoxicillin-clavulanic acid was most frequently prescribed (20.92 DDD/1000 residents/day), followed by the quinolones (14.8 DDD/1000 residents/day). CONCLUSION: We observed a high prevalence of antibiotic resistance and antibiotic use. In particular, the use of and resistance to fluoroquinolones is concerning. Because of the high prevalence of resistance, many agents are no longer suitable for empiric treatment. E. coli ST131, which has also been demonstrated in this study, poses a potential risk to this vulnerable population. We have clearly demonstrated that the resistance among NH residents is different from elderly living at home and hospitalized patients, and with the emergence of resistant strains, such as ST131, NHs are a potential reservoir for multidrug resistant bacteria.

Spread of the epidemic European fusidic acid-resistant impetigo clone (EEFIC) in general practice patients in the south of The Netherlands.

OBJECTIVES: We evaluated the susceptibility to fusidic acid, mupirocin and retapamulin of Staphylococcus aureus isolated from nasal and wound swabs. METHODS: The susceptibility to the three agents of S. aureus isolated from general patients in the south of The Netherlands with a skin or soft tissue infection was determined between January 2007 and December 2008. Fusidic acid-resistant isolates were tested for the presence of fusidic acid-resistant genes and compared with the epidemic European fusidic acid-resistant impetigo clone (EEFIC). RESULTS: Fusidic acid resistance was found in 23% of the nasal and 35% of the wound isolates, the majority (~90%) being fusB positive. Most of the isolates belonged to spa type t171 and were isolated from younger patients. One isolate was retapamulin resistant (MIC 8 mg/L) and two were mupirocin resistant. CONCLUSIONS: The EEFIC clone was relatively highly prevalent among the isolated S. aureus. The usefulness of fusidic acid as first-line agent for the treatment of impetigo is questionable. As mupirocin is used in The Netherlands for eradication of methicillin-resistant S. aureus, it is not an alternative; retapamulin might be useful, but further in vivo studies are warranted.

Predictive value of Escherichia coli susceptibility in strains causing asymptomatic bacteriuria for women with recurrent symptomatic urinary tract infections receiving prophylaxis.

A significant proportion of women develop a recurrence following an initial urinary tract infection (UTI). In women with recurrent UTI, the predictive value of asymptomatic bacteriuria (ASB) for the development of a subsequent UTI has not yet been established and it is not known whether information from an asymptomatic sample is useful in guiding antimicrobial therapy. To address these questions, we used data that originated from the 'Non-antibiotic prophylaxis for recurrent urinary tract infections' (NAPRUTI) study: two randomized controlled trials on the prevention of recurrent UTI in non-hospitalized premenopausal and postmenopausal women (n=445). During 15months of follow-up, no difference was observed in the time to a subsequent UTI between women with and without ASB at baseline (hazard ratio: 1.07, 95% CI 0.80-1.42). The antimicrobial susceptibility and pulsed-field gel-electrophoresis (PFGE) pattern of 50 Escherichia coli strains causing a UTI were compared with those of the ASB strain isolated 1month previously. The predictive values of the susceptibility pattern of the ASB strain, based on resistance prevalence at baseline, were ≥76%, except in the case of nitrofurantoin- and amoxicillin-clavulanic acid-resistance. Asymptomatic and symptomatic isolates had similar PFGE patterns in 70% (35/50) of the patients. In the present study among women with recurrent UTI receiving prophylaxis, ASB was not predictive for the development of a UTI. However, the susceptibility pattern of E. coli strains isolated in the month before a symptomatic E. coli UTI can be used to make informed choices for empirical antibiotic treatment in this patient population.

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.

Diminished in vitro antibacterial activity of oxacillin against clinical isolates of borderline oxacillin-resistant Staphylococcus aureus.

Since it is unknown whether ß-lactam antimicrobial agents can be used effectively against borderline oxacillin-resistant Staphylococcus aureus (BORSA) with oxacillin MICs ≥4 mg/L, the in vitro bactericidal activity and pharmacodynamic effect of oxacillin against clinical BORSA isolates was evaluated. Time-kill experiments with oxacillin were performed and the results compared with those obtained with vancomycin, daptomycin and linezolid against BORSA with oxacillin MICs ≥4 mg/L and BORSA with oxacillin MICs ≤2 mg/L. Furthermore, the effect of ß-lactamase production and plasmid profile analysis were taken into account to clarify responses to oxacillin. Oxacillin killing activity was attenuated against BORSA compared with ATCC 29213 since the pharmacodynamic parameters revealed that the potency of oxacillin was markedly reduced (c. ten-fold) against BORSA with oxacillin MICs ≥4 mg/L. pBORa53-like plasmid-containing BORSA with oxacillin MICs ≤2 mg/L showed markedly more regrowth. In conclusion, oxacillin was non-effective in the eradication of either (i) BORSA with oxacillin MICs ≥4 mg/L or (ii) ß-lactamase-hyperproducing BORSA (MICs ≤2 mg/L). Further investigation into ß-lactam dosing strategies against different BORSA strains is warranted in order to avoid possible therapy failure.

Antibiotic susceptibility of unselected uropathogenic Escherichia coli from female Dutch general practice patients: a comparison of two surveys with a 5 year interval.

OBJECTIVES: To optimize empirical treatment of urinary tract infections (UTIs), regular evaluation of the antibiotic susceptibility of the most common uropathogen, Escherichia coli, is necessary. We compared the antibiotic prescription rate for UTIs in women and the E. coli antibiotic susceptibility results, including the prevalence of extended-spectrum ß-lactamase (ESBL)-producing strains, in 2009 with data collected 5 years earlier. PATIENTS AND METHODS: Urinary samples from female patients with symptoms of uncomplicated UTI in 42 general practices were collected over a 6 month period. Uropathogens were identified and the antibiotic susceptibility of E. coli was determined. RESULTS: We analysed 970 urine cultures, of which 785 (81%) were considered positive (≥ 10(3) cfu/mL). E. coli accounted for 72% of the isolates. ESBLs showed an increase between the two surveys (0.1% versus 1%; P < 0.001), while no difference in antibiotic susceptibility to the commonly used antimicrobial agents for UTIs was observed. A significantly lower susceptibility rate to co-amoxiclav was observed in the eastern region of the Netherlands, as compared with the northern region (80% versus 92%; P <  0.05). Consistent with national guidelines, the prescription rate of trimethoprim decreased over time (19% versus 5%; P  < 0.05) whereas nitrofurantoin and fosfomycin rates showed an increase (58% versus 66% and 0% versus 6% respectively, both P  < 0.05). CONCLUSIONS: Over a 5 year period, the antibiotic susceptibility of uropathogenic E. coli did not change in female patients with uncomplicated UTI in the Netherlands, but ESBL prevalence increased. With respect to the prescription of antimicrobial agents, compliance with national UTI guidelines was good.

Urinary tract infection in male general practice patients: uropathogens and antibiotic susceptibility.

OBJECTIVES: To evaluate uropathogens and their antibiotic susceptibility in male general practitioner (GP) patients presenting with an uncomplicated urinary tract infection (UTI). MATERIAL AND METHODS: A population-based study was conducted among males, 18 years and older, general practice patients, who had symptoms indicative of an uncomplicated UTI. A UTI was defined as >/=10(3) colony-forming units/mL (CFU/mL). The etiology of the infection, antimicrobial susceptibility, and treatment strategies used by the GP were determined. RESULTS: Escherichia coli was most frequently isolated (48%), followed by other enterobacteriaceae (24%) and enterococci (9%). The etiology of infection was age-dependent; E. coli was more frequently isolated in younger patients and Pseudomonas aeruginosa in the elderly. The overall susceptibility rates were low for amoxicillin (63%) and trimethoprim (70%), and high for fluoroquinolones (91%) and amoxicillin-clavulanic acid (90%), which is similar to susceptibility rates in females with UTIs from the same population. Antibiotics were prescribed to 59% of the males with symptoms of UTI. Fluoroquinolones were given to 33% of the patients and trimethoprim-sulfamethoxazole to 24%. No difference in antibiotic prescription, nor in duration of therapy, was found between the different age groups. CONCLUSIONS: In the male presenting with complaints of an acute uncomplicated UTI at the GP, E. coli, followed by other Gram-negative bacteria were the most frequently isolated uropathogens. Susceptibility rates in uncomplicated male and female UTIs were similar, indicating that data from UTI susceptibility studies in females from the same geographic region can be useful in the choice of empirical therapy in males.