Bart Vlaminckx

Appropriateness of Empirical Treatment and Outcome in Bacteremia Caused by Extended-Spectrum-β-Lactamase-Producing Bacteria

ABSTRACT We studied clinical characteristics, appropriateness of initial antibiotic treatment, and other factors associated with day 30 mortality in patients with bacteremia caused by extended-spectrum-β-lactamase (ESBL)-producing bacteria in eight Dutch hospitals. Retrospectively, information was collected from 232 consecutive patients with ESBL bacteremia (due to Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae) between 2008 and 2010. In this cohort (median age of 65 years; 24 patients were <18 years of age), many had comorbidities, such as malignancy (34%) or recurrent urinary tract infection (UTI) (15%). One hundred forty episodes (60%) were nosocomial, 54 (23%) were otherwise health care associated, and 38 (16%) were community acquired. The most frequent sources of infection were UTI (42%) and intra-abdominal infection (28%). Appropriate therapy within 24 h after bacteremia onset was prescribed to 37% of all patients and to 54% of known ESBL carriers. The day 30 mortality rate was 20%. In a multivariable analysis, a Charlson comorbidity index of ≥3, an age of ≥75 years, intensive care unit (ICU) stay at bacteremia onset, a non-UTI bacteremia source, and presentation with severe sepsis, but not inappropriate therapy within <24 h (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 0.68 to 3.45), were associated with day 30 mortality. Further assessment of confounding and a stratified analysis for patients with UTI and non-UTI origins of infection did not reveal a statistically significant effect of inappropriate therapy on day 30 mortality, and these results were insensitive to the possible misclassification of patients who had received β-lactam–β-lactamase inhibitor combinations or ceftazidime as initial treatment. In conclusion, ESBL bacteremia occurs mostly in patients with comorbidities requiring frequent hospitalization, and 84% of episodes were health care associated. Factors other than inappropriate therapy within <24 h determined day 30 mortality.

Longitudinal Analysis of Pneumococcal Antibodies during Community-Acquired Pneumonia Reveals a Much Higher Involvement of Streptococcus pneumoniae than Estimated by Conventional Methods Alone

ABSTRACT In up to half of all cases of community-acquired pneumonia (CAP), no pathogen can be identified with conventional diagnostic methods. The most common identified causative agent is Streptococcus pneumoniae. In this study, pneumococcal antibody responses during CAP were analyzed to estimate the contribution of the pneumococcus to all cases of CAP for epidemiological purposes. Pneumococcal antibodies against 14 different serotypes were measured in serum of hospitalized CAP patients. Patients participated in one of two consecutive clinical trials in a general 600-bed teaching hospital in the Netherlands (between October 2004 and June 2009). A significant pneumococcal immune response was defined as at least a 2-fold increase in antibody concentrations against a single serotype between an early (day 1) and a late (day 30) serum sample of each patient with an end concentration above 0.35 μg/ml. A total of 349 adult CAP patients participated in two consecutive clinical trials. For 200 patients, sufficient serum samples were available to determine antibody responses: 62 pneumococcal pneumonia patients, 57 nonpneumococcal pneumonia patients, and 81 patients with an unidentified causative agent. A significant immune response was detected in 45% (28/62 patients) of pneumococcal pneumonia patients, in 5% (3/57) of nonpneumococcal pneumonia patients, and in 28% (23/81) of patients with an unidentified causative agent. The estimated contribution of pneumococci in patients with an unidentified causative agent was calculated to be 57% (95% confidence interval, 36 to 86%). A substantial fraction of pneumococcal pneumonia patients do not elicit a serotype-specific immune response.

Consequences of switching from a fixed 2 : 1 ratio of amoxicillin/clavulanate (CLSI) to a fixed concentration of clavulanate (EUCAST) for susceptibility testing of Escherichia coli

OBJECTIVES The CLSI recommends a fixed 2 : 1 ratio of co-amoxiclav for broth microdilution susceptibility testing of Enterobacteriaceae, while EUCAST recommends a fixed 2 mg/L clavulanate concentration. The aims of this study were: (i) to determine the influence of a switch from CLSI to EUCAST methodology on Escherichia coli susceptibility rates; (ii) to compare susceptibility results obtained using EUCAST-compliant microdilution with those from disc diffusion and the Etest; and (iii) to evaluate the clinical outcome of patients with E. coli sepsis treated with co-amoxiclav in relation to the susceptibility results obtained using either method. METHODS Resistance rates were determined in three laboratories that switched from CLSI to EUCAST cards with the Phoenix system (Becton Dickinson) as well as in 17 laboratories that continued to use CLSI cards with the VITEK 2 system (bioMérieux). In one laboratory, isolates were simultaneously tested by both the Phoenix system and either disc diffusion (n = 471) or the Etest (n = 113). Medical and laboratory records were reviewed for E. coli sepsis patients treated with co-amoxiclav monotherapy. RESULTS Only laboratories that switched methodology showed an increase in resistance rates - from 19% in 2010 to 31% in 2011 (P < 0.0001). All isolates that tested susceptible by microdilution were also susceptible by disc diffusion or the Etest, but of 326 isolates that tested resistant by microdilution, 43% and 59% tested susceptible by disc diffusion and the Etest, respectively. Among the 89 patients included there was a better correlation between clinical response and measured MICs using the Phoenix system than the Etest. CONCLUSIONS EUCAST methodology resulted in higher co-amoxiclav E. coli resistance rates than CLSI methodology, but correlated better with clinical outcome. EUCAST-compliant microdilution and disc diffusion provided discrepant results.

Incidence of bactobilia increases over time after endoscopic sphincterotomy

Patients with choledochocystolithiasis are usually treated by endoscopic retrograde cholangiography with endoscopic sphincterotomy (ES) followed by laparoscopic cholecystectomy (LC). LC after ES is more difficult than in uncomplicated gallstone disease, possibly due to bacterial colonization of the common bile duct. The goal of this study was to evaluate if bactobilia influences the peri- and postoperative outcomes. Data were obtained from a randomized trial on the timing of LC after ES. Ninety-six patients were randomized after ES to LC either within 72 h (early LC [ELC]) or in 6–8 weeks (delayed LC [DLC]). In 64 of 96 patients bile samples were obtained peroperatively. The overall prevalence of bactobilia was 62.5% [40/64; 50% of ELC patients (n = 13) vs. 71.1% in the DLC group (n = 27); p = 0.088]. Age and group (i.e. ELC/DLC) were independent and significant predictors for the presence of bactobilia. The presence of bactobilia did not influence operating time and difficulty or conversion rate. Patients with bactobilia developed more biliary events in the period between ES and LC (44 vs. 28%). After ES for choledochocystolithiasis, 62.5% of patients have bactobilia at the time of surgery. The prevalence of bactobilia increases with age and time. Patients with bactobilia tend to develop more biliary-related complications awaiting surgery.

Randomized clinical trial of extended versus single-dose perioperative antibiotic prophylaxis for acute calculous cholecystitis

Many patients who have surgery for acute cholecystitis receive postoperative antibiotic prophylaxis, with the intent to reduce infectious complications. There is, however, no evidence that extending antibiotics beyond a single perioperative dose is advantageous. This study aimed to determine the effect of extended antibiotic prophylaxis on infectious complications in patients with mild acute cholecystitis undergoing cholecystectomy.

Strongyloides stercoralis hyperinfection mimicking accelerated form of idiopathic pulmonary fibrosis

Rapidly progressive disease has recently been recognised as a common cause of death in patients with idiopathic pulmonary fi brosis (IPF). IPF is the most prevalent form of idiopathic interstitial pneumonia, and also has the worst prognosis. A 57-year-old man from Suriname with Indian ancestry presented to our hospital with dyspnoea and was diagnosed with IPF after surgical lung biopsy. Leucocyte diff erential count of the blood showed a modest eosinophilia of 15%. Since the patient’s total IgE levels were raised (6·24 g/L; normal range 0–0·24 g/L) and specifi c IgE antibodies were found against house dust mites and pollens, the eosinophilia was explained by concomitant atopy. Because of an assumed rapidly progressive disease, he was treated with methyl prednisolone (1000 mg per day for 3 days) after exclusion of common alternative diagnoses such as opportunistic respiratory infections. During his stay in hospital, the patient had diarrhoea. Strongyloides stercoralis larvae were seen in a stool specimen. Hyperinfection syndrome was suspected and treatment with ivermectin (15 μg/kg) started. 1 day after initiation of ivermectin, our patient died due to respiratory failure. Autopsy results excluded IPF exacerbation as the cause of death. A lung specimen obtained post-mortem showed diff use alveolar damage in the exudative phase with focal organisation (fi gure A). There were areas with chronic infl ammation and marked eosinophilia. Furthermore, S stercoralis larvae were present in these areas of infl ammation and in the lumen of bronchi (fi gure B; arrows). The presence of S stercoralis in our patient’s lung tissue was indicative of hyperinfection syndrome. In the absence of early diagnosis and treatment, the prognosis of complicated strongyloidiasis is very poor. Retrospectively, we undertook an ELISA on serum that was obtained from our patient at disease presentation. S stercoralis antibodies were already detectable in this sample. This case underlines the importance of screening for S stercoralis in patients from endemic regions before starting immunosuppressive therapy. Many doctors trained in the developed world are not very familiar with tropical diseases. However, knowledge is very important since more patients in the Netherlands, and other highincome countries, have immigrated from tropical countries.

Increased incidence of serotype-1 invasive pneumococcal disease in young female adults in The Netherlands

Analysis of the Dutch national invasive pneumococcal disease (IPD) surveillance data by sex reveals an increase in the incidence of serotype-1 disease in young female adults in The Netherlands after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the national immunization schedule. This has led to an overall increase in IPD in women aged 20-45 years, which was not observed in men of the same age. No other differences in serotype shifts possibly induced by the introduction of PCV7 were observed between the sexes in this age group. Serotype 1 is a naturally fluctuating serotype in Europe and it has been associated with disease in young healthy adults before. It remains uncertain whether or not there is an association between the observed increase in serotype-1 disease in young female adults and the implementation of PCV7 in The Netherlands.

Mannose-binding lectin and L-ficolin polymorphisms in patients with community-acquired pneumonia caused by intracellular pathogens

Community‐acquired pneumonia (CAP) is the leading infectious disease requiring hospitalization in the western world. Genetic variability affecting the host response to infection may play a role in susceptibility and outcome in patients with CAP. Mannose‐binding lectin (MBL) and l‐ficolin (l‐FCN) are two important activators of the complement system and they can enhance phagocytosis by opsonization. In a prospective cohort of 505 Dutch patients with CAP and 227 control participants we studied whether polymorphisms in the MBL (MBL2) and FCN (FCN2) genes influenced susceptibility and outcome. No difference in frequency of these genotypes was found between patients with CAP in general and controls. However, the +6424G>T single nucleotide polymorphism (SNP) in FCN2 was more common in patients with a Coxiella burnetii pneumonia (P = 0·014). Moreover, the haplotypes coding for the highest MBL serum levels (YA/YA and YA/XA) predisposed to atypical pneumonia (C. burnetii, Legionella or Chlamydia species or Mycoplasma pneumoniae) compared with controls (P = 0·016). Furthermore, patients with these haplotypes were more often bacteraemic (P = 0·019). It can therefore be concluded that MBL2 and FCN2 polymorphisms are not major risk factors for CAP in general, but that the +6424G>T SNP in the FCN2 gene predisposes to C. burnetii pneumonia. In addition, patients with genotypes corresponding with high serum MBL levels are at risk for atypical pneumonia, possibly caused by enhanced phagocytosis, thereby promoting cell entry of these intracellular bacteria.

Dexamethasone Treatment Has No Effect on the Formation of Pneumococcal Antibodies during Community-Acquired Pneumonia

ABSTRACT In this study, the effect of dexamethasone on the formation of pneumococcal antibodies during community-acquired pneumonia (CAP) was investigated. No differences between CAP patients receiving dexamethasone as additional therapy and patients receiving a placebo were found with respect to immune response rates and mean baseline and convalescent-phase antibody concentrations.

Diagnostic Prediction Tools For Bacteraemia Caused By 3rd Generation Cephalosporin-Resistant Enterobacteriaceae In Suspected Bacterial Infections: A Nested Case-Control Study

Objectives Current antibiotic treatment guidelines on when to consider 3rd generation cephalosporin resistant Enterobacteriaceae (3GC-R EB) as a cause of infection have low specificity, thereby increasing unnecessary carbapenem use. Therefore, we aimed to develop new diagnostic scoring systems to direct initial carbapenem treatment to patients at risk of 3GC-R EB bacteraemia. Methods A retrospective nested case-control study was performed that included patients ≥18 years from 8 Dutch hospitals in whom blood cultures were obtained and intravenous antibiotics were initiated. Patients with 3GC-R EB bacteraemia were each matched to four control infection episodes within the same hospital, based on blood culture date and onset location (community or hospital). Starting from 32 commonly described clinical risk factors available at infection onset, selection strategies were used to derive scoring systems for the probability of community‐ and hospital-onset 3GC-R EB bacteraemia. Results Among 22,506 community-onset and 8,110 hospital-onset infections, respectively 90 (0.4%) and 82 (1.0%) were 3GC-R EB bacteraemias. As control populations, 360 community-onset and 328 hospital-onset infection episodes were included. The derived community-onset and hospital-onset scoring system consisted of 6 and 9 predictors, respectively, and both showed good discrimination with c-statistics of 0.807 and 0.842. Cutoffs for the scores could be chosen such that ~20% of patients would be eligible for empirical carbapenem treatment, which would capture ~70% of those with 3GC-R EB bacteraemia. Conclusions These prediction rules for 3GC-R EB bacteraemia, specifically geared towards the initiation of empiric antibiotic treatment, may improve the balance between inappropriate antibiotics and carbapenem overuse.