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BACKGROUND: Before 2012, established national surveillance systems in the Netherlands were not able to provide a timely, comprehensive epidemiological view on nosocomial outbreaks. The Healthcare-associated Infections and AntiMicrobial Resistance Monitoring Group (SO-ZI/AMR) was initiated in 2012 for timely national nosocomial outbreak monitoring and risk assessment. This paper aims to describe the achievements of the SO-ZI/AMR by presenting characteristics of outbreaks reported in 2012-2021. METHODS: Hospitals and, since 2015, long-term care facilities (LTCF) were requested to report outbreaks when (1) continuity of care was threatened, or (2) transmission continued despite control measures. A multi-disciplinary expert panel (re-)assessed the public health risk of outbreaks during monthly meetings, using 5 severity phases and based on data collected via standardised questionnaires. We descriptively studied the panel's consensus-based severity classification, distribution of (highly resistant) microorganisms, and duration and size of outbreaks between April 2012 and December 2021. RESULTS: In total, 353 hospital outbreaks and 110 LTCF outbreaks were reported. Most outbreaks (hospitals: n = 309 (88%), LTCF: n = 103 (94%)) did not progress beyond phase 1 (no public health implications, outbreak expected to be controlled within two months), one hospital outbreak reached phase 4 (insufficient/ineffective response: possible public health threat, support offered). Highly resistant microorganisms (HRMO) were involved in 269 (76%) hospital and 103 (94%) LTCF outbreaks. Most outbreaks were caused by methicillin-resistant Staphylococcus aureus (MRSA; n = 93 (26%) in hospitals, n = 80 (72%) in LTCF), vancomycin-resistant Enterococcus faecium (VRE; n = 116 (33%) in hospitals, n = 2 (2%) in LTCF) and highly resistant Enterobacterales (n = 41 (12%) in hospitals, n = 20 (18%) in LTCF). Carbapenemase-producing gram-negative bacteria were involved in 32 (9.1%) hospital and five (4.5%) LTCF outbreaks. In hospitals, VRE outbreaks had the longest duration (median 2.3; range 0.0-22.8 months) and widest range of affected patients (median 9; range 2-483). CONCLUSIONS: The SO-ZI/AMR provided national insight into the characteristics of nosocomial outbreaks over the past decade. HRMO outbreaks - mostly caused by MRSA, VRE (in hospitals) and highly resistant Enterobacterales - occurred regularly, but most of them were controlled quickly and did not develop into a public health threat. The SO-ZI/AMR has become a solid monitoring body, essential to assess risks and raise awareness of potential HRMO threats.
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Infecção Hospitalar , Staphylococcus aureus Resistente à Meticilina , Humanos , Infecção Hospitalar/prevenção & controle , Países Baixos/epidemiologia , Hospitais , Surtos de Doenças/prevenção & controle , BactériasRESUMO
BackgroundThe COVID-19 pandemic resulted in adaptation in infection control measures, increased patient transfer, high occupancy of intensive cares, downscaling of non-urgent medical procedures and decreased travelling.AimTo gain insight in the influence of these changes on antimicrobial resistance (AMR) prevalence in the Netherlands, a country with a low AMR prevalence, we estimated changes in demographics and prevalence of six highly resistant microorganisms (HRMO) in hospitalised patients in the Netherlands during COVID-19 waves (March-June 2020, October 2020-June 2021, October 2021-May 2022 and June-August 2022) and interwaves (July-September 2020 and July-September 2021) compared with pre-COVID-19 (March 2019-February 2020).MethodsWe investigated data on routine bacteriology cultures of hospitalised patients, obtained from 37 clinical microbiological laboratories participating in the national AMR surveillance. Demographic characteristics and HRMO prevalence were calculated as proportions and rates per 10,000 hospital admissions.ResultsAlthough no significant persistent changes in HRMO prevalence were detected, some relevant non-significant patterns were recognised in intensive care units. Compared with pre-COVID-19 we found a tendency towards higher prevalence of meticillin-resistant Staphylococcus aureus during waves and lower prevalence of multidrug-resistant Pseudomonas aeruginosa during interwaves. Additionally, during the first three waves, we observed significantly higher proportions and rates of cultures with Enterococcus faecium (pooled 10% vs 6% and 240 vs 120 per 10,000 admissions) and coagulase-negative Staphylococci (pooled 21% vs 14% and 500 vs 252 per 10,000 admissions) compared with pre-COVID-19.ConclusionWe observed no substantial changes in HRMO prevalence in hospitalised patients during the COVID-19 pandemic.
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COVID-19 , Staphylococcus aureus Resistente à Meticilina , Humanos , Países Baixos/epidemiologia , Prevalência , Pandemias , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
OBJECTIVES: Antimicrobial resistant (AMR) infections are a major public health problem and the burden on population level is not yet clear. We developed a method to calculate the excess burden of resistance which uses country-specific parameter estimates and surveillance data to compare the mortality and morbidity due to resistant infection against a counterfactual (the expected burden if infection was antimicrobial susceptible). We illustrate this approach by estimating the excess burden for AMR (defined as having tested positive for extended-spectrum beta-lactamases) urinary tract infections (UTIs) caused by E. coli in the Netherlands in 2018, which has a relatively low prevalence of AMR E. coli, and in Italy in 2016, which has a relatively high prevalence. DESIGN: Excess burden was estimated using the incidence-based disability-adjusted life-years (DALYs) measure. Incidence of AMR E. coli UTI in the Netherlands was derived from ISIS-AR, a national surveillance system that includes tested healthcare and community isolates, and the incidence in Italy was estimated using data reported in the literature. A systematic literature review was conducted to find country-specific parameter estimates for disability duration, risks of progression to bacteraemia and mortality. RESULTS: The annual excess burden of AMR E. coli UTI was estimated at 3.89 and 99.27 DALY/100 0000 population and 39 and 2786 excess deaths for the Netherlands and Italy, respectively. CONCLUSIONS: For the first time, we use country-specific and pathogen-specific parameters to estimate the excess burden of resistant infections. Given the large difference in excess burden due to resistance estimated for Italy and for the Netherlands, we emphasise the importance of using country-specific parameters describing the incidence and disease progression following AMR and susceptible infections that are pathogen specific, and unfortunately currently difficult to locate.
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Anti-Infecciosos , Infecções por Escherichia coli , Infecções Urinárias , Humanos , Escherichia coli , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Resistência Microbiana a Medicamentos , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
OBJECTIVES: Among patients with haematological malignancy, bacteraemia is a common complication during chemotherapy-induced neutropenia. Resistance of gram-negative bacteria (GNB) to third-generation cephalosporins (3GC) is increasing. In order to explore the value of using surveillance cultures to guide empirical treatment e.g. choosing between carbapenem versus ceftazidime- we aimed to assess the distribution of pathogens causing bacteraemia in patients with haematological malignancy, and the proportion of 3GC-resistant GNB (3GC-R GNB) bacteraemia that was preceded by 3GC-R GNB colonization. METHODS: Using 11 years of data (2008-2018) from the Dutch national antimicrobial resistance surveillance system, we assessed the prevalence of 3GC-R GNB in episodes of bacteraemia, and the proportion of 3GC-R GNB bacteraemia that was preceded by 3GC-R GNB colonization. Colonization was defined as availability of any GNB surveillance isolate in the year before, independent of the causative micro-organism (time-paired isolates). RESULTS: We included 3887 patients, representing 4142 episodes of bacteraemia. GNB were identified in 715/4142 (17.3%), of which 221 (30.9%) were 3GC-R GNB. In 139 of these 221 patients a time-paired surveillance culture was available. In 76.2% (106/139) of patients these surveillance cultures already showed 3GC-R GNB isolates in the year prior to the culture date of the 3GC-R GNB positive blood isolate. CONCLUSIONS: This multi-centre study shows that in patients with haematological malignancy, the majority of 3GC-R GNB bacteraemia is preceded by 3GC-R GNB colonization. Prospective clinical studies are needed to assess the safety and benefits of the use of surveillance-cultures to guide empirical therapy to restrict the empirical use of carbapenems in this population.
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Bacteriemia , Neoplasias Hematológicas , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Bacteriemia/tratamento farmacológico , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Carbapenêmicos , CeftazidimaAssuntos
Infecções por Escherichia coli , Escherichia coli , Humanos , Países Baixos/epidemiologia , Escherichia coli/genética , beta-Lactamases/genética , Proteínas de Bactérias/genética , Infecções por Escherichia coli/epidemiologia , Antibacterianos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Background: Colistin is a last-resort treatment option for infections with multidrug-resistant Gram-negative bacteria. However, colistin resistance is increasing. Methods: A six-month prospective matched case-control study was performed in which 22 Dutch laboratories with 32 associated hospitals participated. Laboratories were invited to send a maximum of five colistin-resistant Escherichia coli or Klebsiella pneumoniae (COLR-EK) isolates and five colistin-susceptible isolates (COLS-EK) to the reference laboratory, matched for patient location, material of origin and bacterial species. Epidemiological/clinical data were collected and included in the analysis. Characteristics of COLR-EK/COLS-EK isolates were compared using logistic regression with correction for variables used for matching. Forty-six ColR-EK/ColS-EK pairs were analysed by next-generation sequencing (NGS) for whole-genome multi-locus sequence typing and identification of resistance genes, including mcr genes. To identify chromosomal mutations potentially leading to colistin resistance, NGS reads were mapped against gene sequences of pmrAB, phoPQ, mgrB and crrB. Results: In total, 72 COLR-EK/COLS-EK pairs (75% E. coli and 25% K. pneumoniae) were included. Twenty-one percent of COLR-EK patients had received colistin, in contrast to 3% of COLS-EK patients (OR > 2.9). Of COLR-EK isolates, five contained mcr-1 and two mcr-9. One isolate lost mcr-9 after repeated sub-culturing, but retained colistin resistance. Among 46 sequenced COLR-EK isolates, genetic diversity was large and 19 (41.3%) isolates had chromosomal mutations potentially associated with colistin resistance. Conclusions: Colistin resistance is present but uncommon in the Netherlands and caused by the mcr gene in a minority of COLR-EK isolates. There is a need for surveillance of colistin resistance using appropriate susceptibility testing methods.
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OBJECTIVE: Description of the changing patterns of antibiotic resistance in Helicobacter pylori infection in the Netherlands. DESIGN: Retrospective database study using the Dutch infectious disease surveillance information system-antibiotic resistance (ISIS-AR). METHOD: In the ISIS-AR database antibiotic resistance data are reported by 46 microbiologic laboratories in the Netherlands. For the present study, data from 16 centres were used with a 10 year period of reporting H. pylori resistance data, from 1 January 2010 till 1 January 2020, for amoxycillin, levofloxacin, claritrhromycin, tetracyclin and metronidazole. RESULTS: In 2019 Antimicrobial resistance rates in the Netherlands were 1% for tetracycline, 5% for amoxycillin, 23%% for levofloxacin, 46% for metronidazole and 47% for clarithromycin. The combined resistance rate for clarithromycin and metronidazole was 29%. Significantly higher resistance rates were found in female patients for amoxycillin (8% vs 1%), clarithromycin (53% vs 38%) and metronidazole (52% vs 38%). From 2010 to 2019, a significant rise in resistance rates was found for amoxycillin (0% - 5%), clarithromycin (7% - 40%), metronidazole (14% - 45%) and for the clarithromycin and metronidazole combination (2% - 29%). CONCLUSION: There was an important rise in antibiotic resistance rates in H. pylori in the Netherlands. For optimal H. pylori treatment bismuth-based therapies should become available again in the Netherlands. Treatment of H. pylori should be based on the individual antibiotic resistance profile and be in concordance with the principles of antibiotic stewardship. Guidelines for treatment of H. pylori in the Netherlands should be adapted and have a better correlation with International guidelines and best practices.
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Infecções por Helicobacter , Helicobacter pylori , Amoxicilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana , Feminino , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Humanos , Levofloxacino , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Países Baixos/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: The Netherlands is currently considered a low endemic country for carbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE), experiencing only sporadic hospital outbreaks. This study aims to describe susceptibility to carbapenems and the epidemiology of carbapenemase production in Enterobacterales in the Netherlands in 2017-2019. METHODS: Three complementary nationwide surveillance systems are in place to monitor carbapenem susceptibility in the Netherlands. Routine antimicrobial susceptibility test results from medical microbiology laboratories were used to study phenotypic susceptibility of Escherichia coli and Klebsiella pneumoniae. Pathogen surveillance (of all Enterobacterales species) and mandatory notifications were used to describe the characteristics of CPE positive isolates and affected persons. RESULTS: The prevalence of isolates with gradient strip test-confirmed elevated meropenem (> 0.25 mg/L) or imipenem (> 1 mg/L) minimum inhibitory concentration (MIC) in the Netherlands was very low in 2017-2019, with percentages of 0.06% in E. coli and 0.49% in K. pneumoniae, and carbapenem resistances of 0.02% and 0.18%, respectively. A total of 895 unique species/carbapenemase-encoding allele combinations of CPE from 764 persons were submitted between 2017 and 2019, with the annual number of submissions increasing slightly each year. Epidemiological data was available for 660 persons. Screening because of presumed colonisation risk was the reason for sampling in 70.0% (462/660) of persons. Hospitalization abroad was the most common risk factor, being identified in 45.9% of persons. CONCLUSIONS: Carbapenem resistance of E. coli and K. pneumoniae remains low in the Netherlands. The annual number of CPE isolates slightly increased during the period 2017-2019. Recent hospitalization abroad is the main risk factor for acquisition of CPE.
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Carbapenêmicos , Infecções por Enterobacteriaceae , Proteínas de Bactérias , Carbapenêmicos/farmacologia , Infecções por Enterobacteriaceae/microbiologia , Escherichia coli , Humanos , Klebsiella pneumoniae , Países Baixos/epidemiologia , beta-LactamasesRESUMO
Infections caused by antibiotic-resistant bacteria have become more prevalent during past decades. Yet, it is unknown whether such infections occur in addition to infections with antibiotic-susceptible bacteria, thereby increasing the incidence of infections, or whether they replace such infections, leaving the total incidence unaffected. Observational longitudinal studies cannot separate both mechanisms. Using plasmid-based beta-lactam resistant E. coli as example we applied mathematical modelling to investigate whether seven biological mechanisms would lead to replacement or addition of infections. We use a mathematical neutral null model of individuals colonized with susceptible and/or resistant E. coli, with two mechanisms implying a fitness cost, i.e., increased clearance and decreased growth of resistant strains, and five mechanisms benefitting resistance, i.e., 1) increased virulence, 2) increased transmission, 3) decreased clearance of resistant strains, 4) increased rate of horizontal plasmid transfer, and 5) increased clearance of susceptible E. coli due to antibiotics. Each mechanism is modelled separately to estimate addition to or replacement of antibiotic-susceptible infections. Fitness costs cause resistant strains to die out if other strain characteristics are maintained equal. Under the assumptions tested, increased virulence is the only mechanism that increases the total number of infections. Other benefits of resistance lead to replacement of susceptible infections without changing the total number of infections. As there is no biological evidence that plasmid-based beta-lactam resistance increases virulence, these findings suggest that the burden of disease is determined by attributable effects of resistance rather than by an increase in the number of infections.
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Infecções por Escherichia coli , Escherichia coli , Antibacterianos/farmacologia , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Humanos , Plasmídeos/genética , Resistência beta-Lactâmica/genéticaRESUMO
In this retrospective observational study, we analysed a community outbreak of impetigo with meticillin-resistant Staphylococcus aureus (MRSA), with additional resistance to fusidic acid (first-line treatment). The outbreak occurred between June 2018 and January 2020 in the eastern part of the Netherlands with an epidemiological link to three cases from the north-western part. Forty nine impetigo cases and eight carrier cases were identified, including 47 children. All but one impetigo case had community-onset of symptoms. Pharmacy prescription data for topical mupirocin and fusidic acid and GP questionnaires suggested an underestimated outbreak size. The 57 outbreak isolates were identified by the Dutch MRSA surveillance as MLVA-type MT4627 and sequence type 121, previously reported only once in 2014. Next-generation sequencing revealed they contained a fusidic acid resistance gene, exfoliative toxin genes and an epidermal cell differentiation inhibitor gene. Whole-genome multilocus sequence typing revealed genetic clustering of all 19 sequenced isolates from the outbreak region and isolates from the three north-western cases. The allelic distances between these Dutch isolates and international isolates were high. This outbreak shows the appearance of community-onset MRSA strains with additional drug resistance and virulence factors in a country with a low prevalence of antimicrobial resistance.
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Impetigo , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Criança , Humanos , Ácido Fusídico/uso terapêutico , Ácido Fusídico/farmacologia , Impetigo/tratamento farmacológico , Impetigo/epidemiologia , Meticilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Países Baixos/epidemiologia , Staphylococcus aureus , Surtos de Doenças , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Testes de Sensibilidade MicrobianaRESUMO
Since March 2022, there has been an emergence of multidrug-resistant organisms (MDRO) in the Netherlands in patients originating from Ukraine (58 patients, 75 isolates). For about half of these patients, recent hospitalisation in Ukraine was reported. Genomic surveillance revealed that the majority of the MDRO represent globally spread epidemic lineages and that 60% contain New Delhi metallo-ß-lactamase (NDM) genes. Professionals should be aware of an increase in such MDRO associated with migration and medical evacuation of people from Ukraine.
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Antibacterianos , Farmacorresistência Bacteriana Múltipla , Humanos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Países Baixos/epidemiologia , Ucrânia/epidemiologia , Bactérias Gram-Negativas , beta-Lactamases/genética , Testes de Sensibilidade MicrobianaRESUMO
Verona Integron-encoded Metallo-beta-lactamase (VIM) is the most frequently-encountered carbapenemase in the healthcare-related pathogen Pseudomonas aeruginosa. In the Netherlands, a low-endemic country for antibiotic-resistant bacteria, no national surveillance data on the prevalence of carbapenemase-producing P. aeruginosa (CPPA) was available. Therefore, in 2016, a national surveillance pilot study was initiated to investigate the occurrence, molecular epidemiology, genetic characterization, and resistomes of CPPA among P. aeruginosa isolates submitted by medical microbiology laboratories (MMLs) throughout the country. From 1221 isolates included in the study, 124 (10%) produced carbapenemase (CIM-positive); of these, the majority (95, 77%) were positive for the blaVIM gene using PCR. Sequencing was performed on 112 CIM-positive and 56 CIM-negative isolates (n = 168), and genetic clustering revealed that 75/168 (45%) isolates were highly similar. This genetic cluster, designated Group 1, comprised isolates that belonged to high-risk sequence type ST111/serotype O12, had similar resistomes, and all but two carried the blaVIM-2 allele on an identical class 1 integron. Additionally, Group 1 isolates originated from around the country (i.e. seven provinces) and from multiple MMLs. In conclusion, the Netherlands had experienced a nationwide, inter-institutional, clonal outbreak of VIM-2-producing P. aeruginosa for at least three years, which this pilot study was crucial in identifying. A structured, national surveillance program is strongly advised to monitor the spread of Group 1 CPPA, to identify emerging clones/carbapenemase genes, and to detect transmission in and especially between hospitals in order to control current and future outbreaks.
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Surtos de Doenças , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , beta-Lactamases/genética , Antibacterianos/farmacologia , Geografia Médica , História do Século XXI , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Países Baixos/epidemiologia , Filogenia , Projetos Piloto , Infecções por Pseudomonas/história , Pseudomonas aeruginosa/classificação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Vigilância em Saúde Pública , Resistência beta-Lactâmica , beta-Lactamases/biossínteseRESUMO
BACKGROUND: Carbapenemases produced by Enterobacterales are often encoded by genes on transferable plasmids and represent a major healthcare problem, especially if the plasmids contain additional antibiotic resistance genes. As part of Dutch national surveillance, 50 medical microbiological laboratories submit their Enterobacterales isolates suspected of carbapenemase production to the National Institute for Public Health and the Environment for characterization. All isolates for which carbapenemase production is confirmed are subjected to next-generation sequencing. OBJECTIVES: To study the molecular characteristics of a genetic cluster of Enterobacter cloacae complex isolates collected in Dutch national surveillance in the period 2015-20 in the Netherlands. METHODS: Short- and long-read genome sequencing was used in combination with MLST and pan-genome MLST (pgMLST) analyses. Automated antimicrobial susceptibility testing (AST), the Etest for meropenem and the broth microdilution test for colistin were performed. The carbapenem inactivation method was used to assess carbapenemase production. RESULTS: pgMLST revealed that nine E. cloacae complex isolates from three different hospitals in the Netherlands differed by <20 alleles and grouped in a genetic cluster termed EclCluster-013. Seven isolates were submitted by one hospital in 2016-20. EclCluster-013 isolates produced carbapenemase and were from ST78, a globally disseminated lineage. EclCluster-013 isolates harboured a 316â078 bp IncH12 plasmid carrying the bla VIM-1 carbapenemase and the novel mcr-9 colistin resistance gene along with genes encoding resistance to different antibiotic classes. AST showed that EclCluster-013 isolates were MDR, but susceptible to meropenem (<2 mg/L) and colistin (<2 mg/L). CONCLUSIONS: The EclCluster-013 reported here represents an MDR E. cloacae complex ST78 strain containing an IncH12 plasmid carrying both the bla VIM-1 carbapenemase and the mcr-9 colistin resistance gene.
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Insight into antibiotic prescribing quality is key to general practitioners (GPs) to improve their prescribing behavior and to national antibiotic surveillance and stewardship programs. Additionally to numbers of prescribed antibiotics, quality indicators (QIs) linked to the clinical indication for prescribing are urgently needed. The aim of this proof of concept study was to define indication-linked QIs which can be easily implemented in Dutch primary care by collaborating with data-extraction/processing companies that routinely process patient data for GP practices. An expert group of academic and practicing GPs defined indication-linked QIs for which outcomes can be derived from routine care data. QI outcomes were calculated and fed back to GPs from 44 practices, associations between QI outcomes were determined, and GPs' opinions and suggestions with respect to the new set were captured using an online questionnaire. The new set comprises: (1) total number of prescribed antibiotics per 1000 registered patients and percentages of generally non-1st choice antibiotics; (2) prescribing percentages for episodes of upper and lower respiratory tract infection; (3) 1st choice prescribing for episodes of tonsillitis, pneumonia and cystitis in women. Large inter-practice variation in QI outcomes was found. The validity of the QI outcomes was confirmed by associations that were expected. The new set was highly appreciated by GPs and additional QIs were suggested. We conclude that it proved feasible to provide GPs with informative, indication-linked feedback of their antibiotic prescribing quality by collaborating with established data extraction/processing companies. Based on GPs' suggestions the set will be refined and extended and used in the near future as yearly feedback with benchmarking for GPs and for national surveillance and stewardship purposes.
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Introduction. Increased carbapenem resistance is often caused by carbapenemase production.Aim. The objective of our study was to assess which antibiotic susceptibility patterns, as tested by automated systems, are highly associated with the absence of carbapenemase production in Enterobacteriaceae isolates, and could therefore be used as a screening tool.Methodology. Routine antibiotic susceptibility testing data from 42 medical microbiology laboratories in the Netherlands in the period between January 2011 and June 2017 were obtained from the national antimicrobial resistance surveillance programme. Data on Enterobacteriaceae isolates that had an elevated minimum inhibitory concentration (MIC) for carbapenems (meropenem >0.25 mg l-1 or imipenem >1.0 mg l-1) were selected and subjected to phenotypic or genotypic carbapenemase production testing. Routinely available amoxicillin/clavulanic acid, piperacillin/tazobactam, cefuroxime and ceftriaxone/cefotaxime susceptibilities were studied in relation to carbapenemase production by calculating the negative predictive value.Results. No evidence for carbapenemase-producing Enterobacteriaceae (CPE) was found in 767 of 1007 (76â%) isolates. The negative predictive value was highest for amoxicillin/clavulanic acid (99.6â%) and piperacillin/tazobactam (98.8â%).Conclusion. Enterobacteriaceae isolates with elevated carbapenem MICs that are susceptible to amoxicillin/clavulanic acid or piperacillin/tazobactam are unlikely to be carbapenemase producers. Preselection based on this susceptibility pattern may lead to increased laboratory efficiency and reduction of costs. Whether this is also true for countries with a different distribution of CPE species and types or a higher prevalence of CPE needs to be studied.
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Proteínas de Bactérias/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/metabolismo , Enterobacteriaceae/efeitos dos fármacos , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/patogenicidade , Carbapenêmicos/farmacologia , Enterobacteriaceae/metabolismo , Enterobacteriaceae/patogenicidade , Infecções por Enterobacteriaceae/microbiologia , Humanos , Imipenem , Testes de Sensibilidade Microbiana , Países Baixos , Combinação Piperacilina e Tazobactam , beta-Lactamas/farmacologiaRESUMO
We investigated the prevalence of azole resistance of Aspergillus fumigatus isolates in the Netherlands by screening clinical A. fumigatus isolates for azole resistance during 2013-2018. We analyzed azole-resistant isolates phenotypically by in vitro susceptibility testing and for the presence of resistance mutations in the Cyp51A gene. Over the 6-year period, 508 (11%) of 4,496 culture-positive patients harbored an azole-resistant isolate. Resistance frequency increased from 7.6% (95% CI 5.9%-9.8%) in 2013 (58/760 patients) to 14.7% (95% CI 12.3%-17.4%) in 2018 (112/764 patients) (p = 0.0001). TR34/L98H (69%) and TR46/Y121F/T289A (17%) accounted for 86% of Cyp51A mutations. However, the mean voriconazole MIC of TR34/L98H isolates decreased from 8 mg/L (2013) to 2 mg/L (2018), and the voriconazole-resistance frequency was 34% lower in 2018 than in 2013 (p = 0.0001). Our survey showed changing azole phenotypes in TR34/L98H isolates, which hampers the use of current PCR-based resistance tests.
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Aspergillus fumigatus , Azóis , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergillus fumigatus/genética , Azóis/farmacologia , Farmacorresistência Fúngica , Proteínas Fúngicas/genética , Humanos , Testes de Sensibilidade Microbiana , Países Baixos/epidemiologiaRESUMO
Seven hospitals participated in the Dutch national surveillance for ventilator-associated pneumonia (VAP) and its risk factors. We analysed time-independent and time-dependent risk factors for VAP using the standard Cox regression and the flexible Weighted Cumulative Effects method (WCE) that evaluates both current and past exposures. The prospective surveillance of intensive care patients aged ≥16 years and ventilated ≥48 hours resulted in the inclusion of 940 primary ventilation periods, comprising 7872 ventilation days. The average VAP incidence density was 10.3/1000 ventilation days. Independent risk factors were age (16-40 years at increased risk: HR 2.42 95% confidence interval 1.07-5.50), COPD (HR 0.19 [0.04-0.78]), current sedation score (higher scores at increased risk), current selective oropharyngeal decontamination (HR 0.19 [0.04-0.91]), jet nebulizer (WCE, decreased risk), intravenous antibiotics for selective decontamination of the digestive tract (ivSDD, WCE, decreased risk), and intravenous antibiotics not for SDD (WCE, decreased risk). The protective effect of ivSDD was afforded for 24 days with a delay of 3 days. For some time-dependent variables, the WCE model was preferable over standard Cox proportional hazard regression. The WCE method can furthermore increase insight into the active time frame and possible delay herein of a time-dependent risk factor.
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Antibacterianos/uso terapêutico , Infecção Hospitalar/epidemiologia , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Adolescente , Idoso , Infecção Hospitalar/etiologia , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Humanos , Inalação , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/patologia , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/patologia , Respiração Artificial/efeitos adversos , Fatores de RiscoRESUMO
Background: Direct health effects of antibiotic resistance are difficult to assess. We quantified the risk of recurrent bacteremia associated with resistance. Methods: We extracted antimicrobial susceptibility testing data on blood isolates from the Dutch surveillance system for antimicrobial resistance between 2008 and 2017. First and first recurrent (4-30 days) bacteremia episodes were categorized as susceptible, single nonsusceptible, or co-nonsusceptible to third-generation cephalosporins without or with carbapenems (Enterobacteriaceae), ceftazidime without or with carbapenems (Pseudomonas species), aminopenicillins without or with vancomycin (Enterococcus species), or as methicillin-sensitive/-resistant S. aureus (MSSA/MRSA). We calculated risks of recurrent bacteremia after nonsusceptible vs susceptible first bacteremia, estimated the crude population attributable effect of resistance for the Netherlands, and calculated risks of nonsusceptible recurrent bacteremia after a susceptible first episode. Results: Risk ratios for recurrent bacteremia after a single- and co-nonsusceptible first episode, respectively, vs susceptible first episode, were 1.7 (95% confidence interval [CI], 1.5-2.0) and 5.2 (95% CI, 2.1-12.4) for Enterobacteriaceae, 1.3 (95% CI, 0.5-3.1) and 5.0 (95% CI, 2.9-8.5) for Pseudomonas species, 1.4 (95% CI, 1.2-1.7) and 1.6 (95% CI, 0.6-4.2) for Enterococcus species, and 1.6 (95% CI, 1.1-2.4) for MRSA vs MSSA. The estimated population annual number of recurrent bacteremias associated with nonsusceptibility was 40. The risk of nonsusceptible recurrent bacteremia after a susceptible first episode was at most 0.4% (Pseudomonas species). Conclusions: Although antibiotic nonsusceptibility was consistently associated with higher risks of recurrent bacteremia, the estimated annual number of additional recurrent episodes in the Netherlands (40) was rather limited.
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Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Infecções Bacterianas/microbiologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Farmacorresistência Bacteriana , Humanos , Países Baixos/epidemiologia , Recidiva , Fatores de RiscoRESUMO
Background: In sub-Saharan Africa, 25.5 million people are living with human immunodeficiency virus (HIV), representing 70% of the global total. The need for second-line antiretroviral therapy (ART) is projected to increase in the next decade in keeping with the expansion of treatment provision. Outcome data are required to inform policy. Methods: We performed a systematic review and meta-analysis of studies reporting the virological outcomes of protease inhibitor (PI)-based second-line ART in sub-Saharan Africa. The primary outcome was virological suppression (HIV-1 RNA <400 copies/mL) after 48 and 96 weeks of treatment. The secondary outcome was the proportion of patients with PI resistance. Pooled aggregate data were analyzed using a DerSimonian-Laird random effects model. Results: By intention-to-treat analysis, virological suppression occurred in 69.3% (95% confidence interval [CI], 58.2%-79.3%) of patients at week 48 (4558 participants, 14 studies), and in 61.5% (95% CI, 47.2%-74.9%) at week 96 (2145 participants, 8 studies). Preexisting resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) increased the likelihood of virological suppression. Major protease resistance mutations occurred in a median of 17% (interquartile range, 0-25%) of the virological failure population and increased with duration of second-line ART. Conclusions: One-third of patients receiving PI-based second-line ART with continued NRTI use in sub-Saharan Africa did not achieve virological suppression, although among viremic patients, protease resistance was infrequent. Significant challenges remain in implementation of viral load monitoring. Optimizing definitions and strategies for management of second-line ART failure is a research priority. Prospero Registration: CRD42016048985.
Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Inibidores da Protease de HIV/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , África Subsaariana/epidemiologia , Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral/genética , Feminino , HIV-1 , Humanos , Masculino , Mutação , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resposta Viral Sustentada , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Viremia/tratamento farmacológicoRESUMO
An important cornerstone in the control of antimicrobial resistance (AMR) is a well-designed quantitative system for the surveillance of spread and temporal trends in AMR. Since 2008, the Dutch national AMR surveillance system, based on routine data from medical microbiological laboratories (MMLs), has developed into a successful tool to support the control of AMR in the Netherlands. It provides background information for policy making in public health and healthcare services, supports development of empirical antibiotic therapy guidelines and facilitates in-depth research. In addition, participation of the MMLs in the national AMR surveillance network has contributed to sharing of knowledge and quality improvement. A future improvement will be the implementation of a new semantic standard together with standardised data transfer, which will reduce errors in data handling and enable a more real-time surveillance. Furthermore, the scientific impact and the possibility of detecting outbreaks may be amplified by merging the AMR surveillance database with databases from selected pathogen-based surveillance programmes containing patient data and genotypic typing data.