Antibiotic Resistance and the Risk of Recurrent Bacteremia.

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.

Single-dose compared with multiple day antibiotic prophylaxis for cesarean section in low-resource settings, a randomized controlled, noninferiority trial.

OBJECTIVE: To investigate the efficacy of a single prophylactic dose of ampicillin combined with metronidazole to prevent postcesarean section infections compared with a multiple day regimen in low-resource settings. DESIGN: An evaluator-blinded randomized, controlled, noninferiority trial. SETTING: Two rural hospitals in Tanzania. POPULATION: Of 181 enrolled eligible women with an indication for cesarean section, information on 176 was analyzed by intention-to-treat. METHODS: The women were randomly assigned to either the intervention group who received a single dose of ampicillin and metronidazole, or to the control group who received a multiple-day regimen of ampicillin/amoxicillin and metronidazole. MAIN OUTCOME MEASURES: The primary outcome was maternal postcesarean infection. Secondary outcomes were severity of these infections, other maternal complications, and the duration of hospital stay. RESULTS: In the intervention group (n = 89), six women (6.7%) developed a wound infection compared with nine (10.3%) in the control group (n = 87) (difference 3.60; 95% CI -4.65 to 11.85) (p = 0.40). CONCLUSIONS: A single dose of prophylactic ampicillin and metronidazole is equally effective as a multiple-day regimen in preventing postcesarean wound infections in low-resource settings, therefore it can be considered as a good strategy in low-resource settings. The reduced quantity of prophylactic antibiotics will reduce costs without increasing the risk of maternal infection.

Clustering of antimicrobial resistance outbreaks across bacterial species in the intensive care unit.

BACKGROUND: There are frequent reports of intensive care unit (ICU) outbreaks due to transmission of particular antibiotic-resistant bacteria. Less is known about the burden of outbreaks of resistance due to horizontal transfer of mobile genetic elements between species. Moreover, the potential of existing statistical software as a preliminary means for detecting such events has never been assessed. This study uses a software package to determine the burden of species and resistance outbreaks in 2 adjacent ICUs and to look for evidence of clustering of resistance outbreaks consistent with interspecies transmission of resistance elements. METHODS: A retrospective analysis of data from 2 adjacent 15-bed adult ICUs between 2002 and 2009 was undertaken. Detection of bacterial species-groups and resistance outbreaks was conducted using SaTScan and WHONet-SaTScan software. Resampling and permutation methods were applied to investigate temporal clustering of outbreaks. RESULTS: Outbreaks occurred for 69% of bacterial species-groups (18/26), and resistance outbreaks were detected against 63% of antibiotics (10/16). Resistance outbreaks against 7 of 10 antibiotics were observed in multiple species-groups simultaneously and there was evidence of inter-species-group dependence for 4 of 7 antibiotics; background temporal changes in resistance did not explain the temporal aggregation of outbreaks in 3 of 7 antibiotics. CONCLUSIONS: Species outbreaks occurred for the majority of bacteria commonly identified in the ICU. There was evidence for frequent temporal clustering of resistance outbreaks consistent with interspecies transmission of resistance elements. Wider application of outbreak detection software combined with targeted sequencing of bacterial genomes is needed to understand the contribution of interspecies gene transfer to resistance emergence.

Reliability and validity of multicentre surveillance of surgical site infections after colorectal surgery.

BACKGROUND: Surveillance is the cornerstone of surgical site infection prevention programs. The validity of the data collection and awareness of vulnerability to inter-rater variation is crucial for correct interpretation and use of surveillance data. The aim of this study was to investigate the reliability and validity of surgical site infection (SSI) surveillance after colorectal surgery in the Netherlands. METHODS: In this multicentre prospective observational study, seven Dutch hospitals performed SSI surveillance after colorectal surgeries performed in 2018 and/or 2019. When executing the surveillance, a local case assessment was performed to calculate the overall percentage agreement between raters within hospitals. Additionally, two case-vignette assessments were performed to estimate intra-rater and inter-rater reliability by calculating a weighted Cohen's Kappa and Fleiss' Kappa coefficient. To estimate the validity, answers of the two case-vignettes questionnaires were compared with the answers of an external medical panel. RESULTS: 1111 colorectal surgeries were included in this study with an overall SSI incidence of 8.8% (n = 98). From the local case assessment it was estimated that the overall percent agreement between raters within a hospital was good (mean 95%, range 90-100%). The Cohen's Kappa estimated for the intra-rater reliability of case-vignette review varied from 0.73 to 1.00, indicating substantial to perfect agreement. The inter-rater reliability within hospitals showed more variation, with Kappa estimates ranging between 0.61 and 0.94. In total, 87.9% of the answers given by the raters were in accordance with the medical panel. CONCLUSIONS: This study showed that raters were consistent in their SSI-ascertainment (good reliability), but improvements can be made regarding the accuracy (moderate validity). Accuracy of surveillance may be improved by providing regular training, adapting definitions to reduce subjectivity, and by supporting surveillance through automation.

White matter lesions and lacunar infarcts are independently and differently associated with brain atrophy: the SMART-MR study.

OBJECTIVE: To investigate the independent association of white matter lesions (WML) and lacunar infarcts (LI) with measures of global brain atrophy on MRI. METHODS: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 840 patients (mean age 58 +/- 10 years, 80% male) without cortical, large subcortical or infratentorial infarcts. Brain segmentation was used to quantify volumes of brain tissue, cerebrospinal fluid and WML. Total brain volume, ventricular volume and cortical gray matter volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF), ventricular fraction (VF) and cortical gray matter fraction (GMF). Location and number of infarcts were rated visually. RESULTS: Mean +/- SD BPF was 79.3 +/- 2.8%, mean +/- SD VF was 2.01 +/- 0.95%, and mean +/- SD GMF was 36.6 +/- 3.3%. Linear regression analyses, adjusted for age, sex, vascular risk factors, intima media thickness and LI showed that in patients with moderate to severe WML (upper quartile) BPF was lower (-0.51%; 95% CI -0.93 to -0.08%), VF was higher (0.48%; 95% CI 0.31-0.65%) and GMF was lower (-1.48%; 95% CI -2.07 to -0.88%) than in patients with few WML (lower quartile). Presence of LI was associated with lower BPF (-0.52%; 95% CI -0.96 to -0.07%) and higher VF (0.25%; 95% CI 0.07-0.42%), but not with GMF, independent of WML and other potential confounders. CONCLUSION: WML are associated with total, subcortical and cortical brain atrophy, whereas LI are associated with total and subcortical atrophy, but not with cortical atrophy, suggesting an independent role for WML and LI in the pathogenesis of brain atrophy.

Routinely available antimicrobial susceptibility information can be used to increase the efficiency of screening for carbapenemase-producing Enterobacteriaceae.

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 (76 %) isolates. The negative predictive value was highest for amoxicillin/clavulanic acid (99.6 %) and piperacillin/tazobactam (98.8 %).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.

Blood pressure and decline in kidney function in patients with atherosclerotic vascular disease: a cohort study.

BACKGROUND: Increased blood pressure generally is associated with kidney function decrease. We evaluated the rate of kidney function decrease, the effect of blood pressure on kidney function deterioration, and the possible interaction with albuminuria in patients with vascular disease. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 745 patients with vascular disease from the Second Manifestations of Arterial Disease (SMART) Study. FACTORS: Blood pressure, hypertension presence, albuminuria (albumin-creatinine ratio > 27 mg/g). OUTCOMES: Rate of kidney function decrease, calculated from the difference between 2 estimated glomerular filtration rate (eGFR) values divided by the individual follow-up time. MEASUREMENTS: Participants underwent vascular screening at baseline and after a mean follow-up of 4.5 +/- 1.0 years. Rate of kidney function decrease was expressed as annual decrease in eGFR. Linear regression analysis was used to evaluate the relation between blood pressure and eGFR decrease. RESULTS: Mean baseline eGFR was 79.3 +/- 16.3 mL/min/1.73 m(2), and mean annual decrease in eGFR was 1.00 +/- 2.71 mL/min/1.73 m(2). In 35% of patients, eGFR was stable during follow-up. Albuminuria was present in 100 patients (median albumin-creatinine ratio, 58 mg/g). In patients without albuminuria, age-, sex-, and baseline eGFR-adjusted annual eGFR decrease was 0.86 mL/min/1.73 m(2), whereas this was 1.89 mL/min/1.73 m(2) in patients with albuminuria (P < 0.05). In the presence of albuminuria, higher blood pressure was associated with greater eGFR decrease (beta = 1.29; 95% CI, 0.73-1.85 for systolic blood pressure and beta = 3.86; 95% CI, 2.34-5.38 for hypertension presence). In patients without albuminuria, no association was found between blood pressure and kidney function decrease (beta = 0.15; 95% CI, -0.05 to 0.36 for systolic blood pressure and beta = 0.12; 95% CI, -0.28 to 0.52 for hypertension presence; P for interaction term < 0.05). LIMITATIONS: Participants might reflect a healthier subgroup of patients with vascular disease. Creatinine was measured only twice. CONCLUSIONS: Kidney function decrease in patients with vascular disease is considerable. Blood pressure is a strong risk factor for eGFR decrease in patients with vascular disease and albuminuria.

Metabolic syndrome and vascular risk in patients with peripheral arterial occlusive disease.

OBJECTIVES: Peripheral arterial occlusive disease (PAOD) is associated with a high risk of cardiovascular events. The metabolic syndrome is a frequent condition among patients with manifest vascular disease, but the influence of the metabolic syndrome on cardiovascular events in patients with PAOD is unknown. Also, progression and regression of the metabolic syndrome after follow-up are not extensively studied. METHODS: The study population consisted of 461 patients with symptomatic PAOD from the Second Manifestations of Arterial Disease study (SMART). Patients underwent vascular screening at baseline and after a mean follow-up of 5.5 +/- 1.3 years. Hazard ratios (HRs) for vascular events according to metabolic syndrome status (updated National Cholesterol Education Program [NCEP] criteria) were calculated using Cox regression analysis. The course of the metabolic syndrome during follow-up and the influence of body mass index (BMI) on development or disappearance of the syndrome were assessed. RESULTS: During follow-up, 91 first vascular events were recorded. Cumulative 3-year survival free from vascular events was 84.7% in metabolic syndrome patients compared to 92.1% in participants without the syndrome. The metabolic syndrome was associated with an increased risk of vascular events (HR 1.51; 1.01-2.30, age- and gender-adjusted). During follow-up, 128 patients died or were lost to follow-up, and of 333 remaining patients, 221 participated in follow-up measurements. The metabolic syndrome disappeared in 16% of patients and was incident in 14% of patients during follow-up. Waist circumference increased with 10 +/- 8 cm in those developing the syndrome. A BMI decrease of 1 kg/m(2) significantly decreased the risk of metabolic syndrome development by 23% (odds ratio [OR] 0.77; 0.62-0.96), and increased the chance to revert to a non-metabolic syndrome state by 32% (OR 1.32; 1.03-1.71). CONCLUSION: The metabolic syndrome is associated with a 1.5-fold increase in risk of vascular events in PAOD patients. Weight control reduces metabolic syndrome incidence and increases metabolic syndrome resolution during follow-up.

Direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry improves appropriateness of antibiotic treatment of bacteremia.

Matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows the identification of microorganisms directly from positive blood culture broths. Use of the MALDI-TOF MS for rapid identification of microorganisms from blood culture broths can reduce the turnaround time to identification and may lead to earlier appropriate treatment of bacteremia. During February and April 2010, direct MALDI-TOF MS was routinely performed on all positive blood cultures. During December 2009 and March 2010 no direct MALDI-TOF MS was used. Information on antibiotic therapy was collected from the hospital and intensive care units' information systems from all positive blood cultures during the study period. In total, 253 episodes of bacteremia were included of which 89 during the intervention period and 164 during the control period. Direct performance of MALDI-TOF MS on positive blood culture broths reduced the time till species identification by 28.8-h and was associated with an 11.3% increase in the proportion of patients receiving appropriate antibiotic treatment 24 hours after blood culture positivity (64.0% in the control period versus 75.3% in the intervention period (p0.01)). Routine implementation of this technique increased the proportion of patients on adequate antimicrobial treatment within 24 hours.

Blood pressure, cerebral blood flow, and brain volumes. The SMART-MR study.

BACKGROUND: Low blood pressure (BP) has been related to increased risk of brain atrophy. As brain hypoperfusion might be a marker for impaired cerebral autoregulation, the risk of brain atrophy may be especially increased if BP is low in combination with brain hypoperfusion. We examined whether low BP was associated with brain atrophy and whether this association was stronger in patients with lower parenchymal cerebral blood flow (CBF), as an indicator of brain perfusion. METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study, a cohort study among 1309 patients with atherosclerotic disease, cross-sectional analyses were performed in 965 patients (mean age 58 +/- 10 years) with available BP and CBF measures. Parenchymal CBF was measured with magnetic resonance angiography and was expressed per 100 ml brain volume. Brain segmentation was used to quantify cortical gray matter volume and ventricular volume (% of intracranial volume). RESULTS: Linear regression analyses, adjusted for age, sex, and vascular risk factors showed that the association of systolic BP and pulse pressure, but not diastolic BP, with cortical gray matter volume was modified by parenchymal CBF (P interaction <0.05). In patients with lower parenchymal CBF, but not in those with high parenchymal CBF, lower systolic BP and pulse pressure (per SD decrease) were associated with reduced cortical gray matter volume: beta (95% confidence interval) -0.29% (-0.63; 0.00) and -0.34% (-0.69; -0.01). CONCLUSION: Our findings suggest that lower BP by itself is not sufficient to induce brain atrophy; however, lower SBP and lower pulse pressure in combination with lower parenchymal CBF increased the risk for cortical atrophy.