Lodewijk Spanjaard

Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial

BACKGROUND Selective decontamination of the digestive tract (SDD) is an infection-prevention regimen used in critically ill patients. We assessed the effects of SDD on intensive-care-unit (ICU) and hospital mortality, and on the acquisition of resistant bacteria in adult patients admitted to intensive care. METHODS We did a prospective, controlled, randomised, unblinded clinical trial. 934 patients admitted to a surgical and medical ICU were randomly assigned oral and enteral polymyxin E, tobramycin, and amphotericin B combined with an initial 4-day course of intravenous cefotaxime (SDD group n=466), or standard treatment (controls n=468). Primary endpoints were ICU and hospital mortality and the acquisition of resistant bacteria. FINDINGS In the SDD group 69 (15%) patients died in the ICU compared with 107 (23%) in the control group (p=0.002). Hospital mortality was lower in the SDD groups than in the control group (113 [24%] vs 146 [31%], p=0.02). During their stay in intensive care, colonisation with gram-negative bacteria resistant to ceftazidime, ciprofloxacin, imipenem, polymyxin E, or tobramycin occurred in 61 (16%) of 378 SDD patients and in 104 (26%) of 395 patients in the control group (p=0.001). Colonisation with vancomycin-resistant enterococcus occurred in five (1%) SDD patients and in four (1%) controls (p=1.0). No patient in either group was colonised with meticillin-resistant Staphylococcus aureus. INTERPRETATION In a setting with low prevalence of vancomycin-resistant enterococcus and meticillin-resistant S aureus, SDD can decrease ICU and hospital mortality and colonisation with resistant gram-negative aerobic bacteria.

Clinical features, complications, and outcome in adults with pneumococcal meningitis: a prospective case series

BACKGROUND Bacterial meningitis is a grave disease of high incidence, especially in less developed countries. Here, we describe its clinical presentation, spectrum of complications, prognostic factors, and outcome in adults with pneumococcal meningitis. METHODS From October, 1998, to April, 2002, we assessed 352 episodes of community-acquired pneumococcal meningitis, confirmed by culture of cerebrospinal fluid (CSF), which occurred in patients older than 16 years. Predictors for an unfavourable outcome (Glasgow outcome scale score 1-4) were identified by logistic regression with multiple imputation techniques. FINDINGS 245 (70%) episodes of pneumococcal meningitis were associated with an underlying disorder. Cranial CT was done for 85% of episodes and revealed underlying disorders in 17% (50/299) and meningitis-associated intracranial complications in 39% (117/299). Independent predictors for an unfavourable outcome were a low score on the Glasgow coma scale, cranial nerve palsies, a raised erythrocyte sedimentation rate, a CSF leucocyte count less than 1000 cells per mm(3), and a high CSF protein concentration on admission. Overall in-hospital mortality was 30%. Prevalence of neurological and systemic complications did not differ between patients aged younger than 60 years and those aged 60 years and older; however, systemic complications were the cause of death in 59% (32/54) of fatal episodes in patients aged 60 years and older, whereas neurological complications were the cause of death in 65% (20/31) of fatal episodes in younger patients. INTERPRETATION Pneumococcal meningitis is associated with high mortality and morbidity rates in adults. Whereas neurological complications are the leading cause of death in younger patients, elderly patients die predominantly from systemic complications.

Comparison of extraintestinal pathogenic Escherichia coli strains from human and avian sources reveals a mixed subset representing potential zoonotic pathogens

ABSTRACT Since extraintestinal pathogenic Escherichia coli (ExPEC) strains from human and avian hosts encounter similar challenges in establishing infection in extraintestinal locations, they may share similar contents of virulence genes and capacities to cause disease. In the present study, 1,074 ExPEC isolates were classified by phylogenetic group and possession of 67 other traits, including virulence-associated genes and plasmid replicon types. These ExPEC isolates included 452 avian pathogenic E. coli strains from avian colibacillosis, 91 neonatal meningitis E. coli (NMEC) strains causing human neonatal meningitis, and 531 uropathogenic E. coli strains from human urinary tract infections. Cluster analysis of the data revealed that most members of each subpathotype represent a genetically distinct group and have distinguishing characteristics. However, a genotyping cluster containing 108 ExPEC isolates was identified, heavily mixed with regard to subpathotype, in which there was substantial trait overlap. Many of the isolates within this cluster belonged to the O1, O2, or O18 serogroup. Also, 58% belonged to the ST95 multilocus sequence typing group, and over 90% of them were assigned to the B2 phylogenetic group typical of human ExPEC strains. This cluster contained strains with a high number of both chromosome- and plasmid-associated ExPEC genes. Further characterization of this ExPEC subset with zoonotic potential urges future studies exploring the potential for the transmission of certain ExPEC strains between humans and animals. Also, the widespread occurrence of plasmids among NMEC strains and members of the mixed cluster suggests that plasmid-mediated virulence in these pathotypes warrants further attention.

Community-Acquired Listeria monocytogenes Meningitis in Adults

BACKGROUND Listeria monocytogenes is the third most common cause of bacterial meningitis. METHODS We prospectively evaluated 30 episodes of community-acquired L. monocytogenes meningitis, confirmed by culture of cerebrospinal fluid specimens, in a nationwide study in The Netherlands. Outcome was graded using the Glasgow outcome score; an unfavorable outcome was defined as a score of 1-4. RESULTS We found 30 episodes of L. monocytogenes meningitis. All patients were immunocompromised or > 50 years old. In 19 (63%) of 30 patients, symptoms were present for > 24 h; in 8 patients (27%), symptoms were present for > or = 4 days. The classic triad of fever, neck stiffness, and change in mental status was present in 13 (43%) of 30 patients. An individual cerebrospinal fluid indicator of bacterial meningitis was present in 23 (77%) of 30 cases. Gram staining of cerebrospinal fluid samples revealed the causative organism in 7 (28%) of 25 cases. The initial antimicrobial therapy was amoxicillin based for 21 (70%) of 30 patients. The coverage of initial antimicrobial therapy was microbiologically inadequate for 9 (30%) of the patients. The mortality rate was 17% (5 of 30), and 8 (27%) of 30 patients experienced an unfavorable outcome. Inadequate initial antimicrobial therapy was not related to outcome. CONCLUSIONS In contrast with previous reports, we found that patients with meningitis due to L. monocytogenes do not present with atypical clinical features; however, typical cerebrospinal fluid findings predictive for bacterial meningitis might be absent. A high proportion of patients received initial antimicrobial therapy that did not cover L. monocytogenes.

Phylogenetic Distribution of Virulence-Associated Genes among Escherichia coli Isolates Associated with Neonatal Bacterial Meningitis in The Netherlands

Seventy cerebrospinal fluid Escherichia coli isolates from infants with neonatal bacterial meningitis (NBM), as submitted to the Netherlands Reference Laboratory for Bacterial Meningitis from 1989 through 1997, were assessed for phylogenetic background and extended virulence genotypes, in comparison with the E. coli reference collection, by using molecular methods. Phylogenetic group B2 significantly predominated overall (81%). The 4 major phylogenetic clusters exhibited distinctive virulence genotypes, suggesting diverse evolutionary histories for the individual genes. Many genes not previously studied in NBM, notably diarrhea-associated cdtB (cytolethal distending toxin [46%]) and urinary tract infection-associated ompT (outer membrane protease T [96%]), were as or more prevalent than traditional NBM-associated traits, such as ibeA (invasion of brain endothelium [33%]), sfaS (S fimbriae [59%]), and K1 capsule (81%). These findings provide novel insights into the phylogenetic origins of NBM-associated E. coli and suggest numerous new potential targets for preventive interventions against this dire disease.

Effects of Pneumococcal Conjugate Vaccine 2 Years after Its Introduction, the Netherlands

Vaccine-serotype disease decreased, but non–vaccine-serotype disease increased.

Occurrence of yeast bloodstream infections between 1987 and 1995 in five Dutch university hospitals

The aim of this study was to identify retrospectively trends in fungal bloodstream infections in The Netherlands in the period from 1987 to 1995. Results of over 395,000 blood cultures from five Dutch university hospitals were evaluated. Overall, there were more than 12 million patient days of care during the nine-year study period. The rate of candidemia doubled in the study period, reaching an incidence of 0.71 episodes per 10,000 patient days in 1995. The general increase in candidemia was paralleled by an increase in non-Candida albicans bloodstream infections, mainly due toCandida glabrata. However, more than 60% of the infections were caused byCandida albicans. Fluconazoleresistant species such asCandida krusei did not emerge during the study period. The increasing rate of candidemia found in Dutch university hospitals is similar to the trend observed in the USA, but the rate is lower and the increase is less pronounced.

Protection from routine vaccination at the age of 14 months with meningococcal serogroup C conjugate vaccine in the Netherlands

Routine vaccination with a single dose of conjugated meningococcal C vaccine at 14 months and a catch-up campaign have reduced the incidence of meningococcal C disease in the Netherlands. In contrast to countries where routine vaccination is given in infancy, vaccine failures were not reported. This suggests that one dose of conjugated vaccine in the second year of life might offer longer lasting protection against meningococcal C disease than 3 doses in infancy.

Invasive Pneumococcal Disease among Adults: Associations among Serotypes, Disease Characteristics, and Outcome

BACKGROUND The Streptococcus pneumoniae polysaccharide capsule may be related to invasive pneumococcal disease (IPD) course. METHODS We performed a retrospective cohort study with nationally representative surveillance data from 1075 hospitalized patients with IPD from the Netherlands from 1 June 2004 through 31 May 2006 in the prevaccination era. Serotypes were grouped according to invasive disease potential, rate of the most serious clinical syndromes of meningitis and bacteremia without focus, and case-fatality rates. Multivariable logistic regression analysis was performed to obtain odds ratios adjusted for baseline confounders for the association of serotypes and these outcomes, using the serotypes with the lowest rates as reference. RESULTS IPD caused by serogroups with low invasive disease potential concerned meningitis or bacteremia without focus in 22% of cases, and 74% of patients had an underlying comorbidity. For highly invasive serogroups these figures were 10% (P < .01) and 56% (P < .01). Individual serotypes varied in the relative rate by which they caused meningitis or bacteremia without focus. Compared with the reference group composed of serotypes 1, 5, 7F, 15B, 20, and 33F, the group of serotypes 3, 19F, 23A, 16F, 6B, 9N, and 18C was associated with increased case-fatality rates (group adjusted odds ratio, 2.6; 95% confidence interval, 1.5-4.7). CONCLUSIONS The serotype appeared to be independently associated with IPD severity in adults, which indicates that careful monitoring of IPD after implementation of conjugate vaccines is necessary.

The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial

BACKGROUND In adults with acute stroke, infections occur commonly and are associated with an unfavourable functional outcome. In the Preventive Antibiotics in Stroke Study (PASS) we aimed to establish whether or not preventive antimicrobial therapy with a third-generation cephalosporin, ceftriaxone, improves functional outcome in patients with acute stroke. METHODS In this multicentre, randomised, open-label trial with masked endpoint assessment, patients with acute stroke were randomly assigned to intravenous ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to stroke unit care, or standard stroke unit care without preventive antimicrobial therapy; assignments were made within 24 h after symptom onset. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale and analysed by intention to treat. The primary analysis was by ordinal regression of the primary outcome. Secondary outcomes included death, infection rates, antimicrobial use, and length of hospital stay. Participants and caregivers were aware of treatment allocation but assessors of outcome were masked to group assignment. This trial is registered with controlled-trials.com, number ISRCTN66140176. FINDINGS Between July 6, 2010, and March 23, 2014, a total of 2550 patients from 30 sites in the Netherlands, including academic and non-academic medical centres, were randomly assigned to the two treatment groups: 1275 patients to ceftriaxone and 1275 patients to standard treatment (control group). 12 patients (seven in the ceftriaxone group and five in the control group) withdrew consent immediately after randomisation, leaving 2538 patients available for the intention-to-treat-analysis (1268 in the ceftriaxone group and 1270 in the control group). 2514 (99%) of 2538 patients (1257 in each group) completed 3-month follow-up. Preventive ceftriaxone did not affect the distribution of functional outcome scores on the modified Rankin Scale at 3 months (adjusted common odds ratio 0·95 [95% CI 0·82-1·09], p=0·46). Preventive ceftriaxone did not result in an increased occurrence of adverse events. Overgrowth infection with Clostridium difficile occurred in two patients (<1%) in the ceftriaxone group and none in the control group. INTERPRETATION Preventive ceftriaxone does not improve functional outcome at 3 months in adults with acute stroke. The results of our trial do not support the use of preventive antibiotics in adults with acute stroke. FUNDING Netherlands Organization for Health Research and Development, Netherlands Heart Foundation, and the European Research Council.