Correction to: Bacteria: back pain, leg pain and Modic sign-a surgical multicenter comparative study.

Unfortunately, the 5th author name was incorrectly published in the original paper. The complete correct name is given below.

Bacteria: back pain, leg pain and Modic sign-a surgical multicentre comparative study.

PURPOSE: To compare bacterial findings in pain-generating degenerated discs in adults operated on for lumbar disc herniation (LDH), and mostly also suffering from low back pain (LBP), with findings in adolescent patients with non-degenerated non-pain-generating discs operated on for scoliosis, and to evaluate associations with Modic signs on magnetic resonance imaging (MRI). Cutibacterium acnes (Propionibacterium acnes) has been found in painful degenerated discs, why it has been suggested treating patients with LDH/LBP with antibiotics. As multidrug-resistant bacteria are a worldwide concern, new indications for using antibiotics should be based on solid scientific evidence. METHODS: Between 2015 and 2017, 40 adults with LDH/LBP (median age 43, IQR 33-49) and 20 control patients with scoliosis (median age 17, IQR 15-20) underwent surgery at seven Swedish hospitals. Samples were cultured from skin, surgical wound, discs and vertebrae. Genetic relatedness of C. acnes isolates was investigated using single-nucleotide polymorphism analysis. DNA samples collected from discs/vertebrae were analysed using 16S rRNA-based PCR sequencing. MRI findings were assessed for Modic changes. RESULTS: No bacterial growth was found in 6/40 (15%) LDH patients, compared with 3/20 (15%) scoliosis patients. Most positive samples in both groups were isolated from the skin and then from subcutis or deep within the wound. Of the four disc and vertebral samples from each of the 60 patients, 235/240 (98%) were DNA negative by bacterial PCR. A single species, C. acnes, was found exclusively in the disc/vertebra from one patient in each group. In the LDH group, 29/40 (72%) patients had at least one sample with growth of C. acnes, compared to 14/20 (70%) in the scoliosis group. Bacterial findings and Modic changes were not associated. CONCLUSIONS: Cutibacterium acnes found in discs and vertebrae during surgery for disc herniation in adults with degenerated discs may be caused by contamination, as findings in this group were similar to findings in a control group of young patients with scoliosis and non-degenerated discs. Furthermore, such findings were almost always combined with bacterial findings on the skin and/or in the wound. There was no association between preoperative Modic changes and bacterial findings. Antibiotic treatment of lumbar disc herniation with sciatica and/or low back pain, without signs of clinical discitis/spondylitis, should be seriously questioned. These slides can be retrieved under Electronic Supplementary Material.

Rapid Increase in Carriage Rates of Enterobacteriaceae Producing Extended-Spectrum ß-Lactamases in Healthy Preschool Children, Sweden.

By collecting and analyzing diapers, we identified a >6-fold increase in carriage of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae for healthy preschool children in Sweden (p<0.0001). For 6 of the 50 participating preschools, the carriage rate was >40%. We analyzed samples from 334 children and found 56 containing >1 ESBL producer. The prevalence in the study population increased from 2.6% in 2010 to 16.8% in 2016 (p<0.0001), and for 6 of the 50 participating preschools, the carriage rate was >40%. Furthermore, 58% of the ESBL producers were multidrug resistant, and transmission of ESBL-producing and non-ESBL-producing strains was observed at several of the preschools. Toddlers appear to be major carriers of ESBL producers in Sweden.

Cluster of infections caused by methicillin-resistant Staphylococcus pseudintermedius in humans in a tertiary hospital.

The dog-associated Staphylococcus pseudintermedius is a rare pathogen in humans. Here we describe a cluster of infections caused by the methicillin-resistant S. pseudintermedius clone ST71-J-t02-II-III. It involved four elderly patients at a tertiary hospital. Three patients had wound infections, and the strain had a tendency to cause bullous skin lesions.

Silver resistance genes are overrepresented among Escherichia coli isolates with CTX-M production.

Members of the Enterobacteriaceae with extended-spectrum beta-lactamases (ESBLs) of the CTX-M type have disseminated rapidly in recent years and have become a threat to public health. In parallel with the CTX-M type expansion, the consumption and widespread use of silver-containing products has increased. To determine the carriage rates of silver resistance genes in different Escherichia coli populations, the presence of three silver resistance genes (silE, silP, and silS) and genes encoding CTX-M-, TEM-, and SHV-type enzymes were explored in E. coli isolates of human (n = 105) and avian (n = 111) origin. The antibiotic profiles were also determined. Isolates harboring CTX-M genes were further characterized, and phenotypic silver resistance was examined. The silE gene was present in 13 of the isolates. All of them were of human origin. Eleven of these isolates harbored ESBLs of the CTX-M type (P = 0.007), and eight of them were typed as CTX-M-15 and three as CTX-M-14. None of the silE-positive isolates was related to the O25b-ST131 clone, but 10 out of 13 belonged to the ST10 or ST58 complexes. Phenotypic silver resistance (silver nitrate MIC > 512 mg/liter) was observed after silver exposure in 12 of them, and a concomitant reduced susceptibility to piperacillin-tazobactam developed in three. In conclusion, 12% of the human E. coli isolates but none of the avian isolates harbored silver resistance genes. This indicates another route for or level of silver exposure for humans than that caused by common environmental contamination. Since silE-positive isolates were significantly more often found in CTX-M-positive isolates, it is possible that silver may exert a selective pressure on CTX-M-producing E. coli isolates.

Otitis media: Interactions between host and environment, immune and inflammatory responses.

OBJECTIVE: To review and highlight progress in otitis media (OM) research in the areas of immunology, inflammation, environmental influences and host-pathogen responses from 2019 to 2023. Opportunities for innovative future research were also identified. DATA SOURCES: PubMed database of the National Library of Medicine. REVIEW METHODS: Key topics were assigned to each panel member for detailed review. Search of the literature was from June 2019 until February 2023. Draft reviews were collated, circulated, and discussed among panel members at the 22nd International Symposium on Recent Advances in Otitis Media in June 2023. The final manuscript was prepared and approved by all the panel members. CONCLUSIONS: Important advances were identified in: environmental influences that enhance OM susceptibility; polymicrobial middle ear (ME) infections; the role of adaptive immunity defects in otitis-proneness; additional genes linked to OM; leukocyte contributions to OM pathogenesis and recovery; and novel interventions in OM based on host responses to infection. Innovative areas of research included: identification of novel bacterial genes and pathways important for OM persistence, bacterial adaptations and evolution that enhance chronicity; animal and human ME gene expression, including at the single-cell level; and Sars-CoV-2 infection of the ME and Eustachian tube.

On the etiology of type 1 diabetes: a new animal model signifying a decisive role for bacteria eliciting an adverse innate immunity response.

The cause of type 1 diabetes (T1D) remains unknown; however, a decisive role for environmental factors is recognized. The increased incidence of T1D during the last decades, as well as regional differences, is paralleled by differences in the intestinal bacterial flora. A new animal model was established to test the hypothesis that bacteria entering the pancreatic ductal system could trigger ß-cell destruction and to provide new insights to the immunopathology of the disease. Obtained findings were compared with those present in two patients dying at onset of T1D. Different bacterial species, present in the human duodenum, instilled into the ductal system of the pancreas in healthy rats rapidly induced cellular infiltration, consisting of mainly neutrophil polymorphonuclear cells and monocytes/macrophages, centered around the pancreatic ducts. Also, the islets of Langerhans attracted polymorphonuclear cells, possibly via release of IL-6, IL-8, and monocyte chemotactic protein 1. Small bleedings or large dilatations of the capillaries were frequently found within the islets, and several ß-cells had severe hydropic degeneration (ie, swollen cytoplasm) but with preserved nuclei. A novel rat model for the initial events in T1D is presented, revealing marked similarities with the morphologic findings obtained in patients dying at onset of T1D and signifying a decisive role for bacteria in eliciting an adverse innate immunity response. The present findings support the hypothesis that T1D is an organ-specific inflammatory disease.

Rational use of aminoglycosides--review and recommendations by the Swedish Reference Group for Antibiotics (SRGA).

The Swedish Reference Group for Antibiotics (SRGA) has carried out a risk-benefit analysis of aminoglycoside treatment based on clinical efficacy, antibacterial spectrum, and synergistic effect with beta-lactam antibiotics, endotoxin release, toxicity, and side effects. In addition, SRGA has considered optimal dosage schedules and advice on serum concentration monitoring, with respect to variability in volume of drug distribution and renal clearance. SRGA recommends that aminoglycoside therapy should be considered in the following situations: (1) progressive severe sepsis and septic shock, in combination with broad-spectrum beta-lactam antibiotics, (2) sepsis without shock, in combination with broad-spectrum beta-lactam antibiotics if the infection is suspected to be caused by multi-resistant Gram-negative pathogens, (3) pyelonephritis, in combination with a beta-lactam or quinolone until culture and susceptibility results are obtained, or as monotherapy if a serious allergy to beta-lactam or quinolone antibiotics exists, (4) serious infections caused by multi-resistant Gram-negative bacteria when other alternatives are lacking, and (5) endocarditis caused by difficult-to-treat pathogens when monotherapy with beta-lactam antibiotics is not sufficient. Amikacin is generally more active against extended-spectrum beta-lactamase (ESBL)-producing and quinolone-resistant Escherichia coli than other aminoglycosides, making it a better option in cases of suspected infection caused by multidrug-resistant Enterobacteriaceae. Based on their resistance data, local drug committees should decide on the choice of first-line aminoglycoside. Unfortunately, aminoglycoside use is rarely followed up with audiometry, and in Sweden we currently have no systematic surveillance of adverse events after aminoglycoside treatment. We recommend routine assessment of adverse effects, including hearing loss and impairment of renal function, if possible at the start and after treatment with aminoglycosides, and that these data should be included in hospital patient safety surveillance and national quality registries.

Prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae in healthy Swedish preschool children.

AIM: The objective was to determine the prevalence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in faeces from healthy Swedish preschool children and to establish whether transmission took place between children in preschools. METHODS: Diapers from children attending preschools in Uppsala city were collected during September to October 2010, and the faeces was cultured. Antibiotic profiles and carriage of CTX-M, TEM, SHV and AmpC type enzymes were determined. PCR-positive isolates were further characterized by sequencing and epidemiological typing. Statistics on antibiotic use and ESBL producers in paediatric patients at Uppsala University Hospital were extracted for comparison. RESULTS: A total of 313 stool specimens were obtained, representing 24.5% of all preschool children in Uppsala city. The carriage rate of ESBL-producing Enterobacteriaceae was 2.9% among these healthy children. The corresponding figure for patients in the same age group was 8.4%. Escherichia coli with CTX-M type enzymes predominated, and only one E. coli isolate carried genes-encoding CMY. CTX-M-producing E. coli isolates with identical genotypes were found in children with no familial relation at two different preschools. CONCLUSIONS: Using diapers, the prevalence of ESBL-producing Enterobacteriaceae in children was quickly established, and, most likely, a transmission of ESBL-producing E. coli was for the first time documented between children at the same preschool.

Source Control of Gram-Negative Bacteria Using Self-Disinfecting Sinks in a Swedish Burn Centre.

Several retrospective studies have identified hospital sinks as reservoirs of Gram-negative bacteria. The aim of this study was to prospectively investigate the bacterial transmission from sinks to patients and if self-disinfecting sinks could reduce this risk. Samples were collected weekly from sinks (self-disinfecting, treated with boiling water, not treated) and patients in the Burn Centre at Linköping University Hospital, Sweden. The antibiotic susceptibility of Gram-negative isolates was tested, and eight randomly chosen patient isolates and their connected sink isolates were subjected to whole genome sequencing (WGS). Of 489 sink samples, 232 (47%) showed growth. The most frequent findings were Stenotrophomonas maltophilia (n = 130), Pseudomonas aeruginosa (n = 128), and Acinetobacter spp. (n = 55). Bacterial growth was observed in 20% of the samplings from the self-disinfecting sinks and in 57% from the sinks treated with boiling water (p = 0.0029). WGS recognized one transmission of Escherichia coli sampled from an untreated sink to a patient admitted to the same room. In conclusion, the results showed that sinks can serve as reservoirs of Gram-negative bacteria and that self-disinfecting sinks can reduce the transmission risk. Installing self-disinfecting sinks in intensive care units is an important measure in preventing nosocomial infection among critically ill patients.

The First Swedish Outbreak with VIM-2-Producing Pseudomonas aeruginosa, Occurring between 2006 and 2007, Was Probably Due to Contaminated Hospital Sinks.

Multidrug-resistant Pseudomonas aeruginosa is an increasing clinical problem worldwide. The aim of this study was to describe the first outbreak of a Verona integron-borne metallo-ß-lactamase (VIM)-2-producing P. aeruginosa strain in Sweden and its expansion in the region. A cluster of multidrug-resistant P. aeruginosa appeared at two neighbouring hospitals in 2006. The isolates were characterized by PCR, pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing. Patient charts, laboratory records, and hygiene routines were reviewed, and patients, staff, and the environment were screened. The investigation revealed a clonal outbreak of a VIM-2-producing P. aeruginosa strain belonging to the high-risk clonal complex 111, susceptible only to gentamicin and colistin. No direct contact between patients could be established, but most of them had stayed in certain rooms/wards weeks to months apart. Cultures from two sinks yielded growth of the same strain. The outbreak ended when control measures against the sinks were taken, but new cases occurred in a tertiary care hospital in the region. In conclusion, when facing prolonged outbreaks with this bacterium, sinks and other water sources in the hospital environment should be considered. By implementing proactive control measures to limit the bacterial load in sinks, the waterborne transmission of P. aeruginosa may be reduced.

Antimicrobial drug-resistant Escherichia coli in wild birds and free-range poultry, Bangladesh.

Multidrug resistance was found in 22.7% of Escherichia coli isolates from bird samples in Bangladesh; 30% produced extended-spectrum ß-lactamases, including clones of CTX-M genes among wild and domestic birds. Unrestricted use of antimicrobial drugs in feed for domestic birds and the spread of resistance genes to the large bird reservoir in Bangladesh are growing problems.

Variation-tolerant capture and multiplex detection of nucleic acids: application to detection of microbes.

In contrast to ordinary PCRs, which have a limited multiplex capacity and often return false-negative results due to target variation or inhibition, our new detection strategy, VOCMA (variation-tolerant capture multiplex assay), allows variation-tolerant, target-specific capture and detection of many nucleic acids in one test. Here we demonstrate the use of a single-tube, dual-step amplification strategy that overcomes the usual limitations of PCR multiplexing, allowing at least a 22-plex format with retained sensitivity. Variation tolerance was achieved using long primers and probes designed to withstand variation at known sites and a judicious mix of degeneration and universal bases. We tested VOCMA in situations where enrichment from a large sample volume with high sensitivity and multiplexity is important (sepsis; streptococci, enterococci, and staphylococci, several enterobacteria, candida, and the most important antibiotic resistance genes) and where variation tolerance and high multiplexity is important (gastroenteritis; astrovirus, adenovirus, rotavirus, norovirus genogroups I and II, and sapovirus, as well as enteroviruses, which are not associated with gastroenteritis). Detection sensitivities of 10 to 1,000 copies per reaction were achieved for many targets. VOCMA is a highly multiplex, variation-tolerant, general purpose nucleic acid detection concept. It is a specific and sensitive method for simultaneous detection of nucleic acids from viruses, bacteria, fungi, and protozoa, as well as host nucleic acid, in the same test. It can be run on an ordinary PCR and a Luminex machine and is suitable for both clinical diagnoses and microbial surveillance.

Transfer of an Escherichia coli ST131 multiresistance cassette has created a Klebsiella pneumoniae-specific plasmid associated with a major nosocomial outbreak.

OBJECTIVES: To characterize the complete sequence, horizontal spread and stability of the CTX-M-15-encoding multiresistance plasmid of a Klebsiella pneumoniae strain involved in a large nosocomial outbreak. METHODS: The 220 kbp plasmid pUUH239.2 was completely sequenced using 454 technology. The conjugational host range, conjugation frequencies, plasmid stability and fitness cost of plasmid carriage were studied in vitro. Conjugational spread during the outbreak was assessed retrospectively by multiplex PCR screening, restriction fragment length polymorphism and PFGE. RESULTS: Plasmid pUUH239.2 encodes resistance to ß-lactams (bla(CTX-M-15), bla(TEM-1) and bla(OXA-1)), aminoglycosides [aac-(6')-1b-cr and aadA2], tetracyclines [tet(A) and tetR], trimethoprim (dhfrXII), sulphonamides (sul1), quaternary ammonium compounds (qacEΔ1), macrolides [mph(A)-mxr-mphR(A)] and heavy metal ions (silver, copper and arsenic). The plasmid consists of a backbone, highly similar to the K. pneumoniae plasmid pKPN3, and a 41 kbp resistance region, highly similar to the resistance regions of plasmids pEK499 and pC15-1a previously isolated from Escherichia coli strains belonging to the outbreak lineage ST131 (where ST stands for sequence type). The pUUH239.2 plasmid is stable in K. pneumoniae but unstable in E. coli and confers a fitness cost when introduced into a naive host cell. Transfer of pUUH239.2 from the outbreak K. pneumoniae clone to the E. coli of the patients' intestinal floras has occurred on multiple occasions during the outbreak. CONCLUSIONS: The plasmid pUUH239.2 is a composite of the pKPN3 K. pneumoniae plasmid backbone and the bla(CTX-M-15)-encoding multiresistance cassette associated with the internationally recognized outbreak strain E. coli ST131. The resulting plasmid differs in stability between K. pneumoniae and E. coli, and this has probably limited the spread of this plasmid during the outbreak.

Effects of silver-based wound dressings on the bacterial flora in chronic leg ulcers and its susceptibility in vitro to silver.

Silver-based dressings have been used extensively in wound management in recent years, but data on their antimicrobial activity in the clinical setting are limited. In order to explore their effects on chronic leg ulcer flora, 14 ulcers were cultured after at least 3 weeks treatment with Aquacel Ag(®) or Acticoat(®). Phenotypic and genetic silver resistance were investigated in a total of 56 isolates. Silver-based dressings had a limited effect on primary wound pathogens, which were present in 79% of the cultures before, and 71% after, treatment. One silver-resistant Enterobacter cloacae strain was identified (silver nitrate minimal inhibitory concentration (MIC) > 512 mg/l, positive for silE, silS and silP). Further studies in vitro showed that inducible silver-resistance was more frequent in Enterobacteriaceae with cephalosporin-resistance and that silver nitrate had mainly a bacteriostatic effect on Staphylococcus aureus. Monitoring of silver resistance should be considered in areas where silver is used extensively.

Radical reduction of cephalosporin use at a tertiary hospital after educational antibiotic intervention during an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae.

OBJECTIVES: During an outbreak of extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae at our hospital, we performed an educational antibiotic intervention aimed at reducing prescriptions of second- and third-generation cephalosporins and preventing increased use of fluoroquinolones and carbapenems. In this report, we describe the implementation strategy used and evaluate the intervention effect according to Cochrane recommendations. METHODS: New recommendations for empirical intravenous antibiotic treatment were communicated to prescribers throughout the hospital by infectious diseases physicians working with Strama (the Swedish strategic programme against antibiotic resistance). No restrictive measures were used. The intervention effect was analysed with interrupted time series (ITS) regression analysis of local and national monthly antibiotic sales data. RESULTS: A radical immediate and sustained reduction was demonstrated for the cephalosporins targeted in the intervention, whereas consumption of piperacillin/tazobactam and penicillin G increased substantially. Fluoroquinolone and carbapenem use was essentially unchanged. The ESBL outbreak subsided and no increased resistance to piperacillin/tazobactam was detected in K. pneumoniae, Escherichia coli or Pseudomonas aeruginosa blood isolates during the 2.5 year follow-up. CONCLUSIONS: Our study clearly demonstrates that an educational intervention can have an immediate and profound effect on antibiotic prescription patterns at a large tertiary hospital. ITS regression analysis of local and national antibiotic sales data was valuable to readily assess the immediate and sustained effects of the intervention.

Pneumococcal vaccination in children at risk of developing recurrent acute otitis media - a randomized study.

AIM: Acute otitis media (AOM) is a common childhood disease, which often becomes recurrent (rAOM). A small reduction in AOM episodes has been noted in unselected child cohorts after vaccination with heptavalent conjugate pneumococcal vaccine (PCV7). The purpose of this study was to investigate how vaccination affects young children at risk of developing rAOM. METHODS: Ninety-six children with an AOM onset before 6 months of age, implying a high risk for rAOM, were closely monitored until the age of 2 years. Forty-six were vaccinated with PCV7 and 50 were not. All episodes of AOM, emergency visits and ventilation tube insertions were registered. RESULTS: A total of 363 AOM episodes were diagnosed. The incidence was reduced by 26% (p = 0.03), the number of emergency visits because of suspected AOM by 36% (p = 0.01) and the proportion of children who received ventilation tubes was halved in the vaccine group (p = 0.02). CONCLUSIONS: During the first 2 years of life, PCV7 significantly reduced AOM episodes, emergency visits and ventilation tube insertions in children with rAOM. Pneumococcal vaccine may be a future route to reduce antibiotic use and health care consumption in otitis-prone children.

Foreign travel is a major risk factor for colonization with Escherichia coli producing CTX-M-type extended-spectrum beta-lactamases: a prospective study with Swedish volunteers.

Foreign travel has been suggested to be a risk factor for the acquisition of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. To our knowledge, this has not previously been demonstrated in a prospective study. Healthy volunteers traveling outside Northern Europe were enrolled. Rectal swabs and data on potential travel-associated risk factors were collected before and after traveling. A total of 105 volunteers were enrolled. Four of them did not complete the study, and one participant carried ESBL-producing Escherichia coli before travel. Twenty-four of 100 participants with negative pretravel samples were colonized with ESBL-producing Escherichia coli after the trip. All strains produced CTX-M enzymes, mostly CTX-M-15, and some coproduced TEM or SHV enzymes. Coresistance to several antibiotic subclasses was common. Travel to India was associated with the highest risk for the acquisition of ESBLs (88%; n = 7). Gastroenteritis during the trip was an additional risk factor (P = 0.003). Five of 21 volunteers who completed the follow-up after 6 months had persistent colonization with ESBLs. This is the first prospective study demonstrating that international travel is a major risk factor for colonization with ESBL-producing Enterobacteriaceae. Considering the high acquisition rate of 24%, it is obvious that global efforts are needed to meet the emergence and spread of CTX-M enzymes and other antimicrobial resistances.

Low frequency of antibiotic resistance among urine isolates of Escherichia coli in the community, despite a major hospital outbreak with Klebsiella pneumoniae producing CTX-M-15 in Uppsala County.

A screening programme introduced during a major outbreak of a Klebsiella pneumoniae strain producing extended spectrum beta-lactamase (ESBL), indicated a dissemination of ESBL-producing Escherichia coli in the community. A total of 360 urine samples, yielding 205 isolates, were therefore collected from primary care patients with lower urinary tract infections (UTI) in Uppsala County. The susceptibility pattern of the isolates was investigated with the disk diffusion method. The majority of the positive cultures contained E. coli (76%). Of the members of the Enterobacteriaceae family, only 2 E. coli isolates were resistant to cefpodoxime, of which one produced ESBL. The antibiotic resistance for E. coli isolates was as follows: ampicillin 29.5%, trimethoprim 18.6%, nalidixic acid 7.7%, mecillinam 1.3%, nitrofurantoin 1.3%, and cefpodoxime 1.3%. Approximately 5% of the E. coli isolates showed a combined resistance to 3 or more antibiotic drugs. Negative cultures were common, especially in men, and it was obvious that there were difficulties with the definition of both uncomplicated and lower UTI. In conclusion, a dissemination of ESBL-producing E. coli in the primary care population of Uppsala County could not be confirmed when using urine samples. The antibiotic resistance in E. coli isolates was low overall, with the exception of ampicillin and trimethoprim.

Lack of hygiene routines among patients and family members at patient hotels--a possible route for transmitting puerperal fever.

The use of patient hotels for ambulatory care of women with uncomplicated deliveries has become a routine in Sweden. This report describes a minor outbreak of a group A Streptococcus strain in 2 newly delivered mothers and their newborn babies at a patient hotel.