| 1. |
- Khan, Faisal Ahmad, 1986-
(författare)
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Carbapenemase-Producing Enterobacteriaceae in Wastewater-Associated Aquatic Environments
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The emergence of carbapenem resistance due to the carbapenem-hydrolyzing enzymes (carbapenemases) in Enterobacteriaceae has led to limited therapeutic options. The increased resistance to these “last-resort” antibiotics is fueled by overuse and misuse of antibiotics in human medicine and agriculture. According to the One-Health concept, the microbiomes of humans, animals and natural environments are interconnected reservoirs of antibiotic resistance genes (ARGs) and changes in one compartment will affect the other compartments. Thus, the environmental waters exposed to the pathogens, ARGs and other contaminants of human origin can play a significant role in the spread of resistance. The study aimed to characterize carbapenemase-producing Enterobacteriaceae (CPE) and ARGs in wastewaters and associated river and lake waters in Örebro, Sweden. The study also analyzed de novo development of resistance in Klebsiella oxytoca during long-term growth in river water and the effect of temperature on the emergence of resistance. OXA-48-producing Escherichia coli (ST131) and VIM-1-producing K.oxytoca (ST172) were repeatedly detected in the wastewaters and associated river, suggesting that these isolates were persistently present in these environments. Furthermore, K. oxytoca ST172 isolated from the river was genetically similar to two isolates previously recovered from patients in a local hospital, which shows the possibility of transmission of CPE from hospital to aquatic environments. A high diversity of ARGs was detected in these environments especially in hospital wastewater where ten different carbapenemase genes were detected. These results emphasized that the effective treatment of wastewaters must be ensured to reduce or eliminate the spread of antibiotic resistance. Increased resistance to meropenem (up to 8-fold) and ceftazidime (>10-fold) was observed in K. oxytoca after exposure to both river and tap water after 600 generations and resistance emerged earlier when the bacteria was grown at the higher temperature. The exposure to contaminants and increased environmental temperature may induce similar changes in the environmental microbiome, generating novel resistant variants at accelerated rates that may pose a significant threat to human health.
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| 2. |
- Månsson, Emeli, 1978-
(författare)
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Molecular epidemiology of Staphylococcus epidermidis in prosthetic joint infections
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Staphylococcus epidermidis is ubiquitous in the human microbiota, but also an important pathogen in healthcare-associated infections, such as prosthetic joint infections (PJIs). In this thesis, aspects of the molecular epidemiology of S. epidermidis in PJIs were investigated with the aim of improving our understanding of the pre- and perioperative measures required to reduce the incidence of S. epidermidis PJIs.In Paper I, S. epidermidis retrieved from air sampling in the operating field during arthroplasty was characterized by multilocus sequence typing and antibiotic susceptibility testing. No isolates belonging to sequence types (STs) 2 and 215, previously associated with PJIs, were found in the air of the operating field. During air sampling, several Staphylococcus pettenkoferi isolates were identified, and as a spin-off of Paper I, the genomic relatedness of these isolates to S. pettenkoferi isolates from blood cultures was described in Paper II.In Paper III, genetic traits distinguishing S. epidermidis isolated from PJIs were determined using genome-wide association study accounting for population effects after whole-genome sequencing (WGS) of a population- based 10-year collection of S. epidermidis isolates from PJIs and of nasal isolates retrieved from patients scheduled for arthroplasty. Genes associated with antimicrobial agents used for prophylaxis in arthroplasty, i.e., beta-lactam antibiotics, aminoglycosides, and chlorhexidine, were associated with PJI origin. S. epidermidis from PJIs were dominated by the ST2a, ST2b, ST5, and ST215 lineages.In Paper IV, selective agar plates were used to investigate colonization with methicillin resistant S. epidermidis (MRSE) in patients scheduled for arthroplasty. MRSE were further characterized by WGS. A subset of patients was found to harbour PJI-associated S. epidermidis lineages in their microbiota before hospitalization, but no isolates belonging to the ST2a lineage nor any rifampicin-resistant isolates were retrieved.
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| 3. |
- Sagerfors, Susanna, 1977-
(författare)
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Infectious keratitis : causative microorganisms and how to detect them
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- First, to describe the microbial spectrum in infectious keratitis by both a culture and a targeted sequencing approach; second, to describe the clinical and genetic characteristics of Corynebacterium macginleyi; and third, to study different aspects of the corneal culture process by comparing two instruments used for sampling and two sampling and inoculation strategies. The five studies in this thesis made use of two retrospective study populations and one prospective study population.In the retrospective population the microbial spectrum by corneal culture was explored, Gram-positive bacteria, mainly coagulase-negative staphylococci, Staphylococcus aureus, and Corynebacterium spp. were commonly isolated. In the prospective study population, culture detected 13 different bacterial genera, while targeted sequencing identified a total of 168 different bacterial genera, with individual samples having a median of 13 (7–28) genera. Culture and sequencing showed an 82% agreement on the bacterial genera detected by culture. Genome sequencing and analysis of C. macginleyi revealed two different clades of which the minor clade (n=7), not previously described, exhibited a more complicated disease course. Cotton tipped applicators generated a significantly higher rate (44%) of positive corneal cultures on solid media than knife blades (31%). Direct transferal of multiple corneal samples to culture media generated a significantly higher rate of positive corneal cultures (61%) than indirect transferal through a single transport medium (44%).In conclusion, the microbial spectrum in a Swedish population is similar to previously described in Europe, and C. macginleyi may be considered a corneal pathogen. Targeted sequencing may gain clinical application if further developed. The findings of this thesis indicate that a cotton tipped applicator may be sufficient for corneal sampling for direct inoculation, and the corneal culture procedure can be simplified from seven samplings on four different media to three samplings on two media.
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| 4. |
- Sid Ahmed, Mazen, 1970-
(författare)
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Molecular Epidemiology and Mechanisms of Antibiotic Resistance in Clinical Isolates of Pseudomonas aeruginosa from Qatar
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inappropriate and excessive use of antibiotics promotes antimicrobial resistance (AMR), particularly in Gram-negative bacteria (GNB). There is a noticeable increase in nosocomial infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa, which is associated with significant morbidity, mortality, and an increase in cost management. Although this is a global problem, there is a lack of sufficient data on regional differences that can contribute towards effective AMR management. This thesis presents a study of MDR-P. aeruginosa at five different hospitals in Qatar conducted prospectively between October 2014 - September 2017. The aim was to study the epidemiology, microbiological and clinical characteristics of MDR-P. aeruginosa infections as well as investigate the activity of new antibiotic combinations against these bacteria. The prevalence of MDR-P. aeruginosa isolates in the first year was 8.1% (205/2533), isolated from different clinical specimens, but the majority were from respiratory infections (44.9%, n=92). Most cases were exposed to antibiotics during the 90 days prior to isolation (85.4%, n=177), and the resistance to cefepime, ciprofloxacin, piperacillin/tazobactam, meropenem was >90%. To compare pre- and post-Antimicrobial Stewardship Program, there was a significant reduction in antibiotic consumption by 30.4% of total inpatient antibiotic prescriptions (p=0.008) and the prevalence of MDR-P. aeruginosa significantly declined from 9% to 5.4% (p=0.019). The in vitro investigation of ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) against MDR-P. aeruginosa isolates, showed promising results with susceptibility of 68.8% (n=141/205) and 62.9% (n=129/205), respectively, which was higher than other antipseudomonal agents except colistin. Seventy-five isolates that were sequenced belonged to 29 different sequence types, with ST235 being predominant at 21.3% (16/75). Among the 42 isolates that were resistant to CZA and/or C/T, the most prevalent genes were blaOXA-488 and blaVEB-9 detected in 45.2% (19/42) of isolates. Spearman’s analysis showed that resistance to CZA and C/T were positively correlated with the presence of blaOXA-10, blaPDC-2a, blaVIM-2, and blaVEB-9 , respectively. The study highlights potential key mechanisms that could explain the resistance of MDR-P. aeruginosa to the new antibiotic combinations.
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| 5. |
- Wildeman, Peter, 1975-
(författare)
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Prosthetic Joint Infection of the Hip : Cause and Effect
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Every year, 18 000 patients in Sweden and more than 1 million worldwide undergo total hip arthroplasty (THA). The operation is of great benefit to patients, but is associated with several complications. Prosthetic joint infections (PJIs) are among the most common complications, and can be devastating in terms of suffering for the patient and cost for the healthcare provider. The aim of this thesis was to investigate different aspects of PJIs in order to gain a better understanding of the causes and effects of infection. Four studies were conducted covering genomic analysis of the causative organism, identification of risk factors for failure of treatment, evaluation of a national infection control program aimed at reducing the burden of infections (PRISS: Prosthesis-related infections shall be stopped), and examination of the long-term impact of a PJI on the patient’s health through patient-reported measurement questionnaires.The main findings were as follows. Commensal bacteria such as Cutibacterium avidum have the potential to cause PJIs, and should be specially accounted for when performing hip surgery with an anterior approach. S. aureus is both a commensal and a pathogen with invasive capacity, and the commensal strains do not differ from the PJI strains regarding prevalence of virulence genes and clonal complexes. The genomic traits of pathogens had no impact on treatment success or eradication of infection in S. aureus PJIs The long-term effects of a PJI in the hip include increased mortality, lower quality of life, and decreased hip function. The incidence of PJIs was higher following the PRISS project. Increasing risk factors contributing to PJI explain the increasing incidence of PJI after primary THA.In conclusion, PJIs of the hip have multifactorial causes which are difficult to reduce, and long-term effects are severe.
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| 6. |
- Fagerström, Anna, 1980-
(författare)
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Long-term molecular epidemiology of extended-spectrum β-lactamase producing Escherichia coli in a low-endemic setting
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Escherichia coli is a commensal inhabitant in the gastro-intestinal tract of humans and animals but it is also the most common bacterial species causing urinary tract infection, which ranges in severity from distal cystitis to urosepsis and septic shock. During the past decades, the prevalence of antibiotic resistant E. coli has increased worldwide. Extended-spectrum β-lactamases (ESBL) causes resistance to β-lactam antibiotics, the most widely used class of antibiotics. The genes encoding ESBL, bla, are usually carried on conjugative plasmids, which can be transferred between different bacterial lineages and different species. These plasmids frequently also carry resistance genes to additional antibiotic classes, and ESBL-producing E. coli are therefore often multidrug-resistant. The aim of this thesis was to describe the long-term molecular epidemiology of ESBL-producing E. coli in Örebro County during the time when they first started to emerge. In addition, potential transmission to the environment was investigated by performing a comparative analysis on ESBL-producing E. coli isolated from patients and from the aquatic environment in Örebro city. In general, the E. coli population was genetically diverse, but the pandemic lineage ST131, first identified in 2004, appears to have been responsible for the dramatic increase of CTX-M-15-producing E.coli observed during the late 2000s. CTX-M-15 was the most prevalent ESBL-type followed by CTX-M-14 and these genes were mainly found on plasmids belonging to the IncF or IncI1 families. Continuous horizontal transmission of IncI1 ST31 and ST37 plasmids between diverse E. coli lineages have also contributed to the dissemination of blaCTX-M-15 in Örebro County. Extended spectrum β-lactamase-producing E. coli were found to be common in the aquatic environment in Örebro city and E. coli lineages genetically similar to those causing infections in humans were present in environmental waters indicating that transmission of ESBL-producing E. colifrom humans to the aquatic environment likely has occurred.
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| 7. |
- Tevell, Staffan, 1975-
(författare)
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Staphylococcal prosthetic joint infections : similar, but still different
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Staphylococci constitute a major part of our commensal flora but are also the most common bacteria causing prosthetic joint infections (PJIs), a dreaded complication of arthroplasty surgery. However, not all staphylococci are the same. The virulent Staphylococcus aureus has the ability to cause severe disease such as bacteremia and infective endocarditis in previously healthy people, while the coagulase-negative staphylococci Staphylococcus epidermidis and Staphylococcus capitis rarely act as pathogens unless the patient is immunocompromised or has an implanted medical device, such as a prosthetic joint. This thesis accordingly explores similarities and differences between these three staphylococci in PJIs.S. capitis can cause early postinterventional and chronic PJIs, a finding that has not previously been described. Furthermore, its nosocomial NRCS-A outbreak sublineage, recently observed in neonatal intensive care units, is also present in adult PJIs. When comparing nasal and PJI isolates, the patterns differed between staphylococcal species. In S. capitis, the commensal and infecting strains were separated phylogenetically, while they clustered together for S. aureus. This may indicate diverse reservoirs and acquisition routes in PJIs caused by different staphylococcal species.Outcomes in early postinterventional PJIs were similar in S. capitis and S. aureus infections, with 70–80% achieving clinical cure. In S. aureus infections, no virulence genes were significantly associated with outcome. Although multidrug resistance (MDR) was rare in S. aureus, inability to use biofilm-active antibiotics was a risk factor for failure. However, in S. epidermidis and in the NRCS-A sublineage of S. capitis, MDR and glycopeptide heteroresistance were widespread, highlighting the challenge of antibiotic resistance in the treatment of PJIs.
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| 8. |
- Thunberg, Ulrica, 1967-
(författare)
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Aspects of Staphylococcus aureus in Chronic Rhinosinusitis
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic rhinosinusitis (CRS) affects about 10% of the European population, and is considered a great scourge. Its cause is not clear. Findings of Staphylococcus aureus in the maxillary sinus are common in CRS patients, but are usually regarded as insignificant due to the bacterium’s attribute as a commensal elsewhere. S. aureus has the ability to cause both mild disease and serious conditions, due to its wide armoury of secreted components such as staphylococcal enterotoxins and cell-surface-associated virulence components. This thesis focuses on the clinical features and importance of S. aureus in CRS, including a long-term perspective on the disease, through studying a cohort of CRS patients. S. aureus was found to be highly prevalent in the maxillary sinus and nares of CRS patients, which might indicate an impact on the disease. A sheltered sampling technique for maxillary sinus culture reduced the contamination rate but did not significantly improve the diagnostic reliability. Whole genome sequencing showed that 95% of paired S. aureus isolates collected simultaneously from the nares and maxillary sinus were from identical lineages, indicating colonization of the maxillary sinus from the nares as one joint milieu. A decade-long persistence of S. aureus in the nares and maxillary sinus was established in 20% of CRS patients. The vast majority of S. aureus isolates were susceptible to all tested antibiotics, including the strains that had persisted for a decade. No significant differences in the prevalence of gene determinants were seen for selected virulence factors and MSCRAMMs in S. aureus isolates sampled from CRS patients and healthy controls. The overall alterations of anti-staphylococcal antibodies over time showed great variability and minor support for an impact of S. aureus on CRS. At the long-term follow-up, symptoms were generally reduced and VAS quality of life in terms of fatigue was improved. The subgroup of CRS patients without nasal polyposis had a greater chance of symptom relief than their counterparts with nasal polyposis in this longterm perspective. There was no correlation between severity of symptoms for CRS patients and S. aureus growth in the maxillary sinus to support a role for S. aureus in CRS.
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| 9. |
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| 10. |
- Wistrand, Camilla, 1970-
(författare)
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Swedish operating room nurses preventive interventions to reduce bacterial growth, surgical site infections, and increase comfort in patients undergoing surgery
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Surgical site infection is a major postoperative complication that causes patient suffering and is costly for society. The general aim of this thesis was to test and describe interventions performed by operating room (OR) nurses to prevent bacterial growth in surgical patients, with the intent to prevent surgical site infections (SSIs) whilst increase patients comfort.In studies I and II, 220 pacemaker patients were tested to compare pre-heated skin disinfection with room-temperature skin disinfection regard-ing bacterial growth, skin temperature and patient experience. Preheated skin disinfection was not less effective compared to room-temperature skin disinfection in reducing bacterial growth after skin disinfection and there were no differences regarding SSIs three month postoperatively. Preheated skin disinfection reduces skin heat loss and was perceived as more pleas-ant compared to room-temperature skin disinfection.In study III, 12 OR nurses were examined regarding bacterial growth on their hands and at the sterile glove cuff end after surgical hand disinfec-tion and again after wearing sterile surgical gloves during surgery. They were compared with a control group of 13 non-health care workers. OR nurses’ hands had higher amounts of bacterial growth at two of three culture sites after surgical hand disinfection compared with the control group, and the bacterial growth increased in both groups with time during surgery. There seems to be a risk of bacterial growth at the glove cuff end during surgery, involving the same type of bacteria as isolated from the hands.In study IV, 890 OR nurses answered an online questionnaire describ-ing OR nurses interventions guided by national guidelines to reduce SSIs, such as preparation of the patient skin, patient temperature, and OR ma-terials used. The proportion of the OR nurses who complied with the national guidelines preventive interventions was high: skin disinfection solution (93.5%), drapes (97.4%) and gowns (83.8%), and double gloves (73%). However, when guidelines were lacking the interventions differed.
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