Mortality associated with carbapenem-susceptible and Verona Integron-encoded Metallo-β-lactamase-positive Pseudomonas aeruginosa bacteremia

BACKGROUND: Studies on various Gram-negative bacteria suggest that resistance to carbapenem antibiotics is responsible for increased mortality in patients; however, results are not conclusive. We first assessed the 28-day in-hospital all-cause mortality in patients with Verona Integron-encoded Metallo-β-lactamase-positive Pseudomonas aeruginosa (VIM-PA) bacteremia compared to patients with VIM-negative, carbapenem-susceptible P. aeruginosa (CS-PA) bacteremia. Second, we identified determinants for mortality and survival. METHODS: All patients with a positive blood culture with VIM-PA or CS-PA between January 2004 and January 2016 were included. Kaplan-Meier survival curves were constructed, and survivors and non-survivors were compared on relevant clinical parameters using univariate analyses, and multivariable analyses using a Cox-proportional hazard model. RESULTS: In total, 249 patients were included, of which 58 (23.3%) died. Seventeen out of 40 (42.5%) patients with VIM-PA died, compared to 41 out of 209 (19.6%) patients with CS-PA (difference = 22.9%, P-value = 0.001). Assumed acquisition of the bacterium at the intensive care unit was significantly associated with mortality (HR = 3.32, 95%CI = 1.60-6.87), and having had adequate antibiotic therapy in days 1-14 after the positive blood culture was identified as a determinant for survival (HR = 0.03, 95%CI = 0.01-0.06). VIM-PA vs CS-PA was not identified as an independent risk factor for mortality. CONCLUSIONS: The crude mortality rate was significantly higher in patients with a VIM-PA bacteremia compared to patients with a CS-PA bacteremia; however, when analyzing the data in a multivariable model this difference was non-significant. Awareness of the presence of P. aeruginosa in the hospital environment that may be transmitted to patients and rapid microbiological diagnostics are essential for timely administration of appropriate antibiotics. Acquisition of P. aeruginosa should be prevented, independent of resistance profile

Nowcasting pandemic influenza A/H1N1 2009 hospitalizations in the Netherlands

During emerging epidemics of infectious diseases, it is vital to have up-to-date information on epidemic trends, such as incidence or health care demand, because hospitals and intensive care units have limited excess capacity. However, real-time tracking of epidemics is difficult, because of the inherent delay between onset of symptoms or hospitalizations, and reporting. We propose a robust algorithm to correct for reporting delays, using the observed distribution of reporting delays. We apply the algorithm to pandemic influenza A/H1N1 2009 hospitalizations as reported in the Netherlands. We show that the proposed algorithm is able to provide unbiased predictions of the actual number of hospitalizations in real-time during the ascent and descent of the epidemic. The real-time predictions of admissions are useful to adjust planning in hospitals to avoid exceeding their capacity

Comparing Pandemic to Seasonal Influenza Mortality: Moderate Impact Overall but High Mortality in Young Children

Background: We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed - and thus an underestimation - whereas seasonal influenza mortality is often more inclusively estimated. For a valid comparison, our study used the same statistical methodology and data types to estimate pandemic and seasonal influenza mortality. Methods and Findings: We used data on all-cause mortality (1999-2010, 100% coverage, 16.5 million Dutch population) and influenza-like-illness (ILI) incidence (0.8% coverage). Data was aggregated by week and age category. Using generalized estimating equation regression models, we attributed mortality to influenza by associating mortality with ILI-incidence, while adjusting for annual shifts in association. We also adjusted for respiratory syncytial virus, hot/cold weather, other seasonal factors and autocorrelation. For the 2009 pandemic season, we estimated 612 (range 266-958) influenza-attributed deaths; for seasonal influen

National laboratory-based surveillance system for antimicrobial resistance: a successful tool to support the control of antimicrobial resistance in the Netherlands

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

Use of Antibiotics among Residents Living Close to Poultry or Goat Farms: A Nationwide Analysis in The Netherlands

Prior regional studies found a high risk of pneumonia for people living close to poultry and goat farms. This epidemiological study in the Netherlands used nationwide antibiotic prescription data as a proxy for pneumonia incidence to investigate whether residents of areas with poultry and goat farms use relatively more antibiotics compared to areas without such farms. We used prescription data on antibiotics most commonly prescribed to treat pneumonia in adults and livestock farming data, both with nationwide coverage. Antibiotic use was expressed as defined daily doses per (4-digit Postal Code (PC4) area)-(age group)-(gender)-(month) combination for the year 2015. We assessed the associations between antibiotic use and farm exposure using negative binomial regression. The amoxicillin, doxycycline, and co-amoxiclav use was significantly higher (5-10% difference in use) in PC4 areas with poultry farms present compared to areas without, even after adjusting for age, gender, smoking, socio-economic status, and goat farm presence. The adjusted models showed no associations between antibiotic use and goat farm presence. The variables included in this study could only partly explain the observed regional differences in antibiotic use. This was an ecological study that precludes inference about causal relations. Further research using individual-level data is recommended

Use of Antibiotics among Residents Living Close to Poultry or Goat Farms: A Nationwide Analysis in The Netherlands.

Prior regional studies found a high risk of pneumonia for people living close to poultry and goat farms. This epidemiological study in the Netherlands used nationwide antibiotic prescription data as a proxy for pneumonia incidence to investigate whether residents of areas with poultry and goat farms use relatively more antibiotics compared to areas without such farms. We used prescription data on antibiotics most commonly prescribed to treat pneumonia in adults and livestock farming data, both with nationwide coverage. Antibiotic use was expressed as defined daily doses per (4-digit Postal Code (PC4) area)-(age group)-(gender)-(month) combination for the year 2015. We assessed the associations between antibiotic use and farm exposure using negative binomial regression. The amoxicillin, doxycycline, and co-amoxiclav use was significantly higher (5–10% difference in use) in PC4 areas with poultry farms present compared to areas without, even after adjusting for age, gender, smoking, socio-economic status, and goat farm presence. The adjusted models showed no associations between antibiotic use and goat farm presence. The variables included in this study could only partly explain the observed regional differences in antibiotic use. This was an ecological study that precludes inference about causal relations. Further research using individual-level data is recommended

Spatial analysis of positive and negative Q fever laboratory results for identifying high- and low-risk areas of infection in the Netherlands

Background: The Netherlands faced a large Q fever epidemic from 2007 to 2010, in which thousands of people were tested for the presence of antibodies against Coxiella burnetii as part of individual patient diagnosis. So far, only data of notified cases were used for the identification of high-risk areas, which can lead to misclassification of risk. Therefore, we identified high- and low-risk areas based on laboratory test results to make control measures more efficient. Methods: Data on diagnostic Q fever laboratory tests were obtained from two regional laboratories of medical microbiology in the high-incidence area in the south of the Netherlands. The proportion of patients testing positive was mapped per postal code area. Patients testing positive were compared to patients testing negative based on the distance between residential address and the nearest infected goat farm with adjustment for age and sex. Results and conclusion: Of 11,035 patients tested, 4,011 (36.4%) had a positive laboratory test result for Q fever. Maps showing the spatial pattern of tests performed and proportion of positive tests allowed for the identification of high- and low-risk Q fever areas. The proportion of patients testing positive was higher in areas close to infected goat farms compared to areas further away. Patients living <1 km from an infected goat farm had a substantially higher risk of testing positive for antibodies to C. burnetii than those living >10 km away (OR 21.70, 95% CI 16.28–28.92). Laboratory test results have the potential to make control measures more efficient by identifying high-risk areas as well as low-risk areas

Time to acquire and lose carriership of ESBL/pAmpC producing E. coli in humans in the Netherlands.

A subset of the study population from a cross-sectional study of carriership of ESBL/pAmpC-producing E. coli (ESBL-E) in the general population was followed up by five successive samples over an approximate half year period, leading to six samples in 333 persons. Fecal samples were cultured and analyzed for the presence of E. coli types as characterized by MLST, and ESBL/pAmpC genes were analysed by PCR and sequencing. The study included 255 persons who had a negative first sample, to allow observations of acquiring carriership of ESBL-E. Any individual record thus consisted of a series of snapshots of episodes of presence and absence of ESBL-E carriage. A survival model was built to estimate times to acquire or lose carriership, allowing for any combination of ESBL/pAmpC gene and E. coli MLST type. In carriers, the mean time to lose carriership was 1.1 (95% range 0.8-1.6) years. The estimated mean time to acquire carriership was 3.0 (95% range 1.6-6.3) years. Analysis of these times by ESBL/pAmpC gene found substantial variation among resistance genes both in persistence of carriership and in rates of acquiring carriership: blaCTX-M-1, blaCTX-M-14, blaCTX-M-15, blaCTX-M-27 and blaSHV-12 were easily acquired, but blaCTX-M-1 and blaSHV-12 were also easily lost, while blaCTX-M-15, blaCTX-M-27 and blaCMY-2 were more likely to persist. When in addition bacterial host types were included, some combinations appeared more persistent than others (blaCTX-M-1 in ST10 and ST58; blaCTX-M-14, blaCMY-2, and blaSHV-12 in ST69), or were acquired with higher frequency (blaCTX-M-14 in ST38, ST69, and ST131; blaCTX-M-15 and blaCTX-M-27 in ST131; blaSHV-12 in ST69). The relatively short duration of carriership means that when an intervention drastically reduces the exposure of humans to ESBL-E, the prevalence will be halved in 0.66 years. The observed differences between carriage rates of ESBL/pAmpC genes and E. coli strains need further investigation

Correction: Time to acquire and lose carriership of ESBL/pAmpC producing E. coli in humans in the Netherlands.

[This corrects the article DOI: 10.1371/journal.pone.0193834.]