[Lyme Disease - Laboratory Diagnostics]. / Lyme-Borreliose.

Lyme Disease - Laboratory Diagnostics Abstract. Lyme borreliosis is caused by Borrelia burgdorferi. Laboratory testing for Borrelia-specific antibodies is crucial for the diagnosis of Lyme borreliosis in addition to clinical definitions. The diagnostic approach consists of a two-tier testing: firstly, a highly sensitive screening test such as an enzyme immunoassay and secondly, a highly specific confirmatory assay such as a line immunoblot. The screening test detects Borrelia-specific IgM and IgG antibodies but also unspecific antibodies or cross-reactive antibodies against Treponema (causative agent of syphilis). Thus, a reactive screening test always needs confirmation by a specific test such as the immunoblot thereby resolving specific antibodies against different Borrelia antigens. Moreover, the characteristic spectrum of bands in the immunoblot provides evidence to divide the immune response into an early or a late stage of the disease. For the diagnosis of Lyme neuroborreliosis, intrathecal antibody production to B. burgdorferi should be determined by analyzing paired serum and cerebrospinal fluid samples obtained on the same timepoint. Diagnostics of Lyme borreliosis requires a comprehensive report of Borrelia-specific antibody responses and clinical manifestations.

Identifying patients at high risk for multidrug-resistant organisms after hospitalization abroad.

OBJECTIVES: We quantified the percentage of multidrug-resistant organism (MDRO) carriers among repatriated patients. We identified factors associated with MDRO carriage, and we evaluated the yield of MDRO detection per screened body site. DESIGN: Retrospective cohort study. SETTING: A tertiary-care center in Switzerland. PATIENTS: Adult patients after a stay in a healthcare institution abroad. METHODS: Patients were screened for MDRO carriage. Standard sites, including nose and throat, groins, and (since mid-2018) rectum, and risk-based sites (wounds, urine, tracheal secretion) were sampled. MDROs were defined as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum ß-lactamase (ESBL)- and carbapenemase-producing Enterobacterales (CPE), multidrug-resistant (MDR) Enterobacterales, and MDR nonfermenting gram-negative rods. Risk factors for MDRO carriage were assessed using multivariate logistic regression. RESULTS: Between May 2017 and April 2019, 438 patients were screened and 107 (24.4%) tested positive for an MDRO, predominantly ESBL-producing and MDR Enterobacterales. Risk factors for MDRO colonization were the length of stay in hospital abroad, antibiotic treatment with 'Watch' and 'Reserve' antibiotics, and region of hospitalization abroad. Rectal swabs had the highest yield for detecting patients with MDR intestinal bacteria, but nose/throat and groins, or wound samples were more sensitive for MRSA or nonfermenting gram-negative organisms, respectively. CONCLUSIONS: We identified risk factors for MDRO carriage and body sites with the highest yield for a specific MDRO, which might help to target screening and isolation and reduce screening costs.

Organized crime groups: A systematic review of individual-level risk factors related to recruitment.

Background: Studies from multiple contexts conceptualize organized crime as comprising different types of criminal organizations and activities. Notwithstanding growing scientific interest and increasing number of policies aiming at preventing and punishing organized crime, little is known about the specific processes that lead to recruitment into organized crime. Objectives: This systematic review aimed at (1) summarizing the empirical evidence from quantitative, mixed methods, and qualitative studies on the individual-level risk factors associated with the recruitment into organized crime, (2) assessing the relative strength of the risk factors from quantitative studies across different factor categories and subcategories and types of organized crime. Methods: We searched published and unpublished literature across 12 databases with no constraints as to date or geographic scope. The last search was conducted between September and October 2019. Eligible studies had to be written in English, Spanish, Italian, French, and German. Selection Criteria: Studies were eligible for the review if they: Reported on organized criminal groups as defined in this review.Investigated recruitment into organized crime as one of its main objectives.Provided quantitative, qualitative, or mixed methods empirical analyses.Discussed sufficiently well-defined factors leading to recruitment into organized crime.Addressed factors at individual level.For quantitative or mixed-method studies, the study design allowed to capture variability between organized crime members and non-members. Data Collection and Analysis: From 51,564 initial records, 86 documents were retained. Reference searches and experts' contributions added 116 additional documents, totaling 202 studies submitted to full-text screening. Fifty-two quantitative, qualitative, or mixed methods studies met all eligibility criteria. We conducted a risk-of-bias assessment of the quantitative studies while we assessed the quality of mixed methods and qualitative studies through a 5-item checklist adapted from the CASP Qualitative Checklist. We did not exclude studies due to quality issues. Nineteen quantitative studies allowed the extraction of 346 effect sizes, classified into predictors and correlates. The data synthesis relied on multiple random effects meta-analyses with inverse variance weighting. The findings from mixed methods and qualitative studied were used to inform, contextualize, and expand the analysis of quantitative studies. Results: The amount and the quality of available evidence were weak, and most studies had a high risk-of-bias. Most independent measures were correlates, with possible issues in establishing a causal relation with organized crime membership. We classified the results into categories and subcategories. Despite the small number of predictors, we found relatively strong evidence that being male, prior criminal activity, and prior violence are associated with higher odds of future organized crime recruitment. There was weak evidence, although supported by qualitative studies, prior narrative reviews, and findings from correlates, that prior sanctions, social relations with organized crime involved subjects, and a troubled family environment are associated with greater odds of recruitment. Authors' Conclusions: The available evidence is generally weak, and the main limitations were the number of predictors, the number of studies within each factor category, and the heterogeneity in the definition of organized crime group. The findings identify few risk factors that may be subject to possible preventive interventions.

Rapid Detection of PBP2a in Staphylococci from Shortly Incubated Subcultures of Positive Blood Cultures by an Immunochromatographic Assay.

Staphylococcus aureus, as well as coagulase-negative staphylococci (CoNS), can cause a wide range of human infections both in nosocomial and community settings. Βeta-lactams are the antibiotics of choice for the treatment of bloodstream infections (BSI) caused by these microorganisms. Resistance to virtually all ß-lactams (also referred to as methicillin resistance) primarily results from the production of an alternative penicillin-binding protein (PBP2a) encoded by the mecA gene. While ß-lactams are still used as first-line therapy against BSI caused by S. aureus, BSI with CoNS are usually treated with vancomycin due to the high prevalence of methicillin resistance. Rapid detection of methicillin resistance is thus critical for continuation or adjustment of the empirical therapy and therewith to improve the clinical outcome of the patients. The revised version of the immunochromatographic assay PBP2a SA culture colony test (SACCT) is a rapid, inexpensive, and easy method that enables reliable detection of PBP2a in mecA-positive staphylococcal isolates after18 to 24 h of incubation. Here, we evaluated the diagnostic performance of the SACCT using primary subcultures of spiked blood cultures after short incubation (4 to 6 h) and established a modified procedure with an equal analytical performance to that of longer-grown cultures. With the proposed method the SACCT can be employed for PBP2a detection from shortly incubated subcultures of clinically relevant staphylococcal isolates, thereby allowing more rapid and effective management of BSI caused by these organisms. IMPORTANCE Antibiotic resistance poses a major threat to health and incurs high economic costs worldwide. Rapid detection of resistance mechanisms can contribute to improving patient care and preventing the dissemination of antimicrobial resistance. Here, we describe a rapid method to detect the most important beta-lactam resistance mechanism (the plasmid-encoded alternative transpeptidase PBP2a) in staphylococcal isolates causing BSI. We show that, using a modified procedure, PBP2a can be reliably detected from primary subcultures of spiked blood cultures after short incubation (4 to 6 h) with a rapid, inexpensive, and simple immunochromatographic test (SACCT). We provide an accurate, inexpensive, and rapid method to facilitate appropriate management and control of infections in patients suffering from invasive staphylococcal infections.

Co-occurrence of aminoglycoside and ß-lactam resistance mechanisms in aminoglycoside- non-susceptible Escherichia coli isolated in the Zurich area, Switzerland.

The co-occurrence of aminoglycoside and ß-lactam resistance was assessed in 3358 consecutive Escherichia coli clinical isolates collected in 2014 in the greater Zurich area, Switzerland. Non-susceptibility to at least one of the tested aminoglycosides was observed in 470/3358 E. coli strains (14%). In strains categorized as broad-spectrum ß-lactamase (BSBL)-producers (1241/3358 isolates), extended-spectrum ß-lactamase (ESBL)-producers (262/3358) and AmpC-producers (66/3358), resistance to aminoglycoside was found in 23%, 52% and 20% of the isolates, respectively. In contrast, aminoglycoside-susceptible strains were rarely resistant to ß-lactams (33/1777, 1.9%). The genomes of 439 aminoglycoside-resistant E. coli were sequenced and aminoglycoside and ß-lactam genotypes were analysed. The most prevalent aminoglycoside resistance genes were aph(3')-Ia (133 strains, 30.3%), aac(3)-IId (100 strains, 22.8%), and aac(6')-Ib-cr (52 strains, 11.8%). The most frequent associations with ß-lactam resistance genes were aph(3')-Ia or aac(3)-IId with blaTEM-1 (94 and 72 strains, respectively), and aac(3)-IIa/aac(6')-Ib-cr with blaCTX-M-15/blaOXA-1 (23 strains). These results indicate a frequent association of aac(3) and aph(3') genotypes with BSBL production, and a frequent co-occurrence of aac(6') genes with ESBL production. The high rate of co-occurrence of aminoglycoside resistance and ß-lactamase production must be considered in combination therapy.

The effect of varying multidrug-resistence (MDR) definitions on rates of MDR gram-negative rods.

Background: A multitude of definitions determining multidrug resistance (MDR) of Gram-negative organisms exist worldwide. The definitions differ depending on their purpose and on the issueing country or organization. The MDR definitions of the European Centre for Disease Prevention and Control (ECDC) were primarily chosen to harmonize epidemiological surveillance. The German Commission of Hospital Hygiene and Infection Prevention (KRINKO) issued a national guideline which is mainly used to guide infection prevention and control (IPC) measures. The Swiss University Hospital Zurich (UHZ) - in absentia of national guidelines - developed its own definition for IPC purposes. In this study we aimed to determine the effects of different definitions of multidrug-resistance on rates of Gram-negative multidrug-resistant organisms (GN-MDRO). Methods: MDR definitions of the ECDC, the German KRINKO and the Swiss University Hospital Zurich were applied on a dataset comprising isolates of Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Pseudomonas aeruginosa, and Acinetobacter baumannii complex. Rates of GN-MDRO were compared and the percentage of patients with a GN-MDRO was calculated. Results: In total 11'407 isolates from a 35 month period were included. For Enterobacterales and P. aeruginosa, highest MDR-rates resulted from applying the 'ECDC-MDR' definition. 'ECDC-MDR' rates were up to four times higher compared to 'KRINKO-3/4MRGN' rates, and up to six times higher compared to UHZ rates. Lowest rates were observed when applying the 'KRINKO-4MRGN' definitions. Comparing the 'KRINKO-3/4MRGN' with the UHZ definitions did not show uniform trends, but yielded higher rates for E. coli and lower rates for P. aeruginosa. On the patient level, the percentages of GN-MDRO carriers were 2.1, 5.5, 6.6, and 18.2% when applying the 'KRINKO-4MRGN', 'UHZ-MDR', 'KRINKO-3/4MRGN', and the 'ECDC-MDR' definition, respectively. Conclusions: Different MDR-definitions lead to considerable variation in rates of GN-MDRO. Differences arise from the number of antibiotic categories required to be resistant, the categories and drugs considered relevant, and the antibiotic panel tested. MDR definitions should be chosen carefully depending on their purpose and local resistance rates, as definitions guiding isolation precautions have direct effects on costs and patient care.

Population-based inference of aminoglycoside resistance mechanisms in Escherichia coli.

BACKGROUND: Interpretative reading of antimicrobial susceptibility test (AST) results allows inferring biochemical resistance mechanisms from resistance phenotypes. For aminoglycosides, however, correlations between resistance pathways inferred on the basis of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints and expert rules versus genotypes are generally poor. This study aimed at developing and validating a decision tree based on resistance phenotypes determined by disc diffusion and based on epidemiological cut-offs (ECOFFs) to infer the corresponding resistance mechanisms in Escherichia coli. METHODS: Phenotypic antibiotic susceptibility of thirty wild-type and 458 aminoglycoside-resistant E. coli clinical isolates was determined by disc diffusion and the genomes were sequenced. Based on well-defined cut-offs, we developed a phenotype-based algorithm (Aminoglycoside Resistance Mechanism Inference Algorithm - ARMIA) to infer the biochemical mechanisms responsible for the corresponding aminoglycoside resistance phenotypes. The mechanisms inferred from susceptibility to kanamycin, tobramycin and gentamicin were analysed using ARMIA- or EUCAST-based AST interpretation and validated by whole genome sequencing (WGS) of the host bacteria. FINDINGS: ARMIA-based inference of resistance mechanisms and WGS data were congruent in 441/458 isolates (96·3%). In contrast, there was a poor correlation between resistance mechanisms inferred using EUCAST CBPs/expert rules and WGS data (418/488, 85·6%). Based on the assumption that resistance mechanisms can result in therapeutic failure, EUCAST produced 63 (12·9%) very major errors (vME), compared to only 2 (0·4%) vME with ARMIA. When used for detection and identification of resistance mechanisms, ARMIA resolved >95% vMEs generated by EUCAST-based AST interpretation. INTERPRETATION: This study demonstrates that ECOFF-based analysis of AST data of only four aminoglycosides provides accurate information on the resistance mechanisms in E. coli. Since aminoglycoside resistance mechanisms, despite having in certain cases a minimal effect on the minimal inhibitory concentration, may compromise the bactericidal activity of aminoglycosides, prompt detection of resistance mechanisms is crucial for therapy. Using ARMIA as an interpretative rule set for editing AST results allows for better predictions of in vivo activity of this drug class.