Olav B. Natås

Nosocomial outbreak of CTX-M-15-producing E. coli in Norway.

Seven E. coli isolates expressing resistance to 3rd generation cephalosporins were recovered from blood (n=2), kidney and lung tissue (n=1), and urinary tract (n=4) samples from seven patients hospitalised or recently discharged from the Divisions of Geriatrics and Pulmonary Medicine, Central Hospital of Rogaland, between July and September 2004. All isolates expressed a typical ESBL‐cefotaximase profile (cefotaxime MIC>ceftazidime MIC) with clavulanic acid synergy. A blaCTX‐M‐15 genotype was confirmed in six strains that were coresistant to gentamicin, nitrofurantoin, trimethoprim‐sulfamethoxazole and ciprofloxacin. A blaCTX‐M‐3 genotype was detected in the last strain. XbaI‐PFGE patterns of the six blaCTX‐M‐15 isolates revealed a clonal relationship. BlaCTX‐M‐15 strains were also positive for the ISEcp1‐like insertion sequences that have been shown to be involved in the mobilization of blaCTX‐M. Further analyses revealed two blaCTX‐M‐15‐positive E. coli urinary isolates clonally related to the outbreak strain from two different patients at the same divisions in January and February 2004. These patients were later re‐hospitalised and one had E. coli with an ESBL‐cefotaximase profile in sputum and nasopharyngeal specimen during the outbreak period. Clinical evaluation suggests that the CTX‐M‐producing E. coli strains contributed to death in three patients due to delayed efficient antimicrobial therapy. The outbreak emphasises the epidemic potential of multiple‐antibiotic‐resistant CTX‐M‐15‐producing E. coli also in a country with low antibiotic usage and low prevalence of antimicrobial resistance.

Long-term faecal carriage in infants and intra-household transmission of CTX-M-15-producing Klebsiella pneumoniae following a nosocomial outbreak

OBJECTIVES To investigate the duration of faecal carriage of CTX-M-15-producing Klebsiella pneumoniae in infants colonized during a nosocomial neonatal intensive care unit (NICU) outbreak after discharge from hospital, possible risk factors for long-term colonization and transmission to household contacts (HCs). METHODS Fifty-one infants colonized with two unrelated clones of CTX-M-15 K. pneumoniae [sequence type (ST) 17 and ST485] during an NICU outbreak and 60 HCs provided faecal and rectal samples, respectively, every 1-3 months after hospital discharge. Extended-spectrum β-lactamase (ESBL)-producing strains of K. pneumoniae were identified on Chrom ID ESBL agar and examined by antimicrobial susceptibility testing. blaCTX-M-15 was detected by PCR and DNA sequencing. Clonal relationship was examined by PFGE. RESULTS The median carriage time in infants after discharge was 12.5 months (IQR 9.5-17.5). Stable antimicrobial susceptibility patterns in PFGE-related strains confirmed the intestinal persistence of both outbreak strains. Risk factors for prolonged faecal carriage in infants were delivery by caesarean section [hazard ratio (HR) 2.4, 95% CI 1.1-5.5, P = 0.029] and treatment with antibiotics during hospitalization (HR 4.5, 95% CI 1.6-12.6, P = 0.004). Transmission of CTX-M-15 K. pneumoniae was observed in 9/28 (32%) households. Median carriage length in parents was 2.5 months (IQR 1.0-5.0) (P < 0.001 compared with infants). CONCLUSIONS Infants may be long-term faecal carriers of ESBL-producing K. pneumoniae after colonization during hospitalization in the neonatal period. Delivery by caesarean section and antibiotic treatment during hospitalization are possible risk factors for prolonged carriage. Faecal ESBL carriage in infants represents a reservoir for intra-household spread of ESBL-producing K. pneumoniae.

Acute facial nerve palsy in children: How often is it Lyme borreliosis?

Acute facial nerve palsy in children may be caused by infection by Borrelia burgdorferi, but the incidence of facial nerve palsy and the proportion of facial nerve palsy caused by Lyme borreliosis may vary considerably between areas. Furthermore, it is not well known how often facial nerve palsy caused by Lyme borreliosis is associated with meningitis. In this population-based study, children admitted for acute facial nerve palsy to Stavanger University Hospital during 9 y from 1996 to 2004 were investigated by a standard protocol including a lumbar puncture. A total of 115 children with facial nerve palsy were included, giving an annual incidence of 21 per 100,000 children. 75 (65%) of these were diagnosed as Lyme borreliosis, with all cases occurring from May to November. Lymphocytic meningitis was present in all but 1 of the children with facial nerve palsy caused by Lyme borreliosis where a lumbar puncture was performed (n = 73). In this endemic area for Borrelia burgdorferi, acute facial nerve palsy in children was common. The majority of cases were caused by Lyme borreliosis, and nearly all of these were associated with lymphocytic meningitis.

Laboratory data in children with Lyme neuroborreliosis, relation to clinical presentation and duration of symptoms

The occurrence of IgM and IgG antibodies against Borrelia burgdoferi in serum and cerebrospinal fluid (CSF) and intrathecal synthesis of antibodies (antibody index) were studied in relation to clinical presentation and the duration of symptoms before diagnosis in 146 children diagnosed with neuroborreliosis. Lymphocytic meningitis was demonstrated in 141 of these children. Levels of white blood cells (WBC) and protein in CSF correlated significantly to numbers of d with symptoms. Children were divided into 3 clinical groups: A (n = 37): only cranial neuropathy; B (n = 68): both cranial neuropathy and other neurological symptoms; C (n = 41): neurological symptoms without cranial neuropathy. Levels of WBC and protein in CSF as well as the proportion of children with antibodies in serum and CSF were generally lowest in group A, intermediate in group B and highest in group C. The proportion of children with antibodies in serum and CSF and a positive antibody index was also related to duration of symptoms; the antibody index was present in 51% of children with symptoms ≤ 7 d, and in 80% of children with symptoms > 7 d (p<0.01). The clinical presentation and duration of symptoms must be considered when interpreting laboratory data in children with suspected neuroborreliosis.

First outbreak of extended-spectrum β-lactamase-producing Klebsiella pneumoniae in a Norwegian neonatal intensive care unit; associated with contaminated breast milk and resolved by strict cohorting.

Neonatal intensive care units (NICUs) are vulnerable to nosocomial outbreaks caused by multiresistant Enterobacteriaceae, but no reports of NICU outbreaks of extended‐spectrum β‐lactamase (ESBL) producing Klebsiella pneumoniae have previously been published from countries with a low level of antimicrobial resistance such as the Scandinavian countries. We describe a clonal outbreak of CTX‐M‐15 ‐producing Klebsiella pneumoniae affecting 58 infants in the neonatal intensive care unit at Stavanger University Hospital, Norway, during a period of 4 months, 2008–2009. The clone spread widely and rapidly in the NICU, and extensive interventions were required to terminate the outbreak. In contrast to previous outbreaks, only one infant acquired a systemic infection caused by the outbreak strain, probably due to a favourable epidemic strain lacking the most common virulence factors. A probable index case was identified, due to multiple positive breast milk samples collected from the infants mother before and after the infants transfer from another hospital. Breast milk samples from 3/18 (17%) mothers of colonized infants were positive for ESBL‐producing K. pneumoniae. Vertical transmission of ESBL‐producing bacteria has been shown previously,’but the possibility of transmission of ESBL‐producing K. pneumoniae through expressed breast milk is reported here for the first time. The increasing occurrence of ESBL‐producing’Enterobacteriaceae should therefore encourage changes in diagnostic routines for bacterial screening of breast milk.

Low Faecal Carrier Rate of Vancomycin Resistant Enterococci in Norwegian Hospital Patients

The faecal carrier rate of vancomycin resistant enterococci (VRE) was surveyed among 616 patients in selected departments of 7 Norwegian hospitals. One Enterococcus gallinarum isolate harbouring a vanB2 element was recovered from a child with malignant disease treated with vancomycin and ceftazidime. No vancomycin resistant Enterococcus faecalis or Enterococcus faecium were detected and no VRE isolates of the VanA type were identified. The low level of VRE carriage corresponds to the limited use of glycopeptide antibiotics for human therapeutic purposes in Norway. It indicates a low risk of acquiring VRE infections in Norwegian hospitals.

Quantification of Clostridium difficile in Antibiotic-Associated-Diarrhea Patients

ABSTRACT Comparing culture- and non-culture-based methods for quantifying Clostridium difficile in antibiotic-associated-diarrhea patients, we found that the real-time PCR method correlated well with quantitative culture and was more sensitive. A positive association between the population levels of C. difficile and the presence of its toxins was found.

Emergence of clonally related multidrug resistant Haemophilus influenzae with penicillin-binding protein 3-mediated resistance to extended-spectrum cephalosporins, Norway, 2006 to 2013

Resistance to cephalosporins in Haemophilus influenzae is usually caused by characteristic alterations in penicillin-binding protein 3 (PBP3), encoded by the ftsI gene. Resistance to extended-spectrum cephalosporins is associated with high-level PBP3-mediated resistance (high-rPBP3), defined by the second stage S385T substitution in addition to a first stage substitution (R517H or N526K). The third stage L389F substitution is present in some high-rPBP3 strains. High-rPBP3 H. influenzae are considered rare outside Japan and Korea. In this study, 30 high-rPBP3 isolates from Norway, collected between 2006 and 2013, were examined by serotyping, multilocus sequence typing (MLST), ftsI sequencing, detection of beta-lactamase genes and minimum inhibitory concentration (MIC) determination. MICs were interpreted according to clinical breakpoints from the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Respiratory isolates predominated (proportion: 24/30). The 30 isolates included one serotype f isolate, while the remaining 29 lacked polysaccharide capsule genes. Resistance to extended-spectrum cephalosporins (cefixime, 29 isolates/30 isolates; cefepime, 28/30; cefotaxime, 26 /30; ceftaroline, 26/30; ceftriaxone, 14/30), beta-lactamase production (11/30) and co-resistance to non-beta-lactams (trimethoprim-sulfamethoxazole, 13/30; tetracycline, 4/30; chloramphenicol, 4/30; ciprofloxacin, 3/30) was frequent. The N526K substitution in PBP3 was present in 23 of 30 isolates; these included a blood isolate which represents the first invasive S385T + N526K isolate reported from Europe. The L389F substitution, present in 16 of 30 isolates, coincided with higher beta-lactam MICs. Non-susceptibility to meropenem was frequent in S385T + L389F + N526K isolates (8/12). All 11 beta-lactamase positive isolates were TEM-1. Five clonal groups of two to 10 isolates with identical MLST-ftsI allelic profiles were observed, including the first reported high-rPBP3 clone with TEM-1 beta-lactamase and co-resistance to ciprofloxacin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole. Prior to this study, no multidrug resistant high-rPBP3 H. influenzae had been reported in Norway. Intensified surveillance of antimicrobial resistance is needed to guide empiric therapy.

Lyme meningitis, the major cause of childhood meningitis in an endemic area: a population based study.

Objective To evaluate the epidemiology of infectious meningitis in children in a Lyme borreliosis (LB) endemic area, and to study how clinical and laboratory characteristics may distinguish between different types of childhood meningitis. Design Retrospective, population based study. Setting A paediatric department serving all children (62 000) in a costal LB endemic region of southwestern Norway. Patients All children with cerebrospinal fluid pleocytosis aged 3 months to 14 years. Main outcome measures Epidemiological, clinical and laboratory characteristics of different types of childhood meningitis. Results Infectious meningitis was diagnosed in 211 children (annual incidence 38/100 000). Lyme meningitis (LM) was identified in 142 children (67%), non-Lyme aseptic meningitis in 46 children (22%) and bacterial meningitis in 23 children (11%). Age, month of admission and clinical and laboratory characteristics differed between the groups. An aetiological agent was found in 89% of children. The positive predictive value for having LM if the child had facial nerve palsy or head and/or neck stiffness (meningism) as the only symptom was 97% for both variables. Symptoms of cerebral involvement or signs of systemic inflammation were rare in children with LM compared to children non-Lyme aseptic meningitis. Conclusion LM was diagnosed in two-thirds of children with infectious meningitis in this LB endemic area. Distinct clinical characteristics distinguished the majority of children with LM from children with non-Lyme aseptic meningitis and bacterial meningitis.

Extended-spectrum β-lactamase-producing Enterobacteriaceae among pregnant women in Norway: prevalence and maternal-neonatal transmission.

Objective:To study (i) the prevalence and risk factors for carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) in pregnant women, (ii) the maternal–neonatal transmission rate of ESBL-E at birth and (iii) the prevalence of ESBL-E in expressed breast milk of colonized mothers.Study design:In this cross-sectional, population-based study with case follow-up on maternal–neonatal transmission of ESBL-E, women were screened for rectal ESBL-E colonization at 36 weeks of pregnancy and delivery. Possible risk factors for colonization were studied by logistic regression. Infants of ESBL-E-positive mothers were screened for ESBL-E during their first weeks of life. ESBL-encoding genes were detected by PCR and clonal relatedness was investigated by pulsed-field gel electrophoreses.Results:In total, 26 out of 901 (2.9%) women were colonized by ESBL-producing Escherichia coli at 36 weeks of pregnancy. One of the women carried an additional ESBL Klebsiella pneumoniae strain. Adjusted for traveling, African or Asian nationality was a risk factor for colonization; OR=5.62 (2.21, 14.27) (LR-p=0.003). Fourteen women remained ESBL-E carriers at delivery. ESBL-E strains indistinguishable from the strains isolated from their respective mothers were detected in 5 (35.7%) infants during their first days of life (median day 3; range=2 to 8). A total of 146 expressed milk samples were cultured from 25 out of 26 colonized mothers, all were ESBL-E negative.Conclusions:The prevalence of ESBL-E carriage among pregnant women was low in our region, but the high maternal–neonatal transmission rate suggests that colonized mothers represent a substantial risk for infant colonization.