Genomic surveillance as a scalable framework for precision phage therapy against antibiotic-resistant pathogens.

Phage therapy is gaining increasing interest in the fight against critically antibiotic-resistant nosocomial pathogens. However, the narrow host range of bacteriophages hampers the development of broadly effective phage therapeutics and demands precision approaches. Here, we combine large-scale phylogeographic analysis with high-throughput phage typing to guide the development of precision phage cocktails targeting carbapenem-resistant Acinetobacter baumannii, a top-priority pathogen. Our analysis reveals that a few strain types dominate infections in each world region, with their geographical distribution remaining stable within 6 years. As we demonstrate in Eastern Europe, this spatiotemporal distribution enables preemptive preparation of region-specific phage collections that target most local infections. Finally, we showcase the efficacy of phage cocktails against prevalent strain types using in vitro and animal infection models. Ultimately, genomic surveillance identifies patients benefiting from the same phages across geographical scales, thus providing a scalable framework for precision phage therapy.

Novel motivational interviewing-based intervention improves engagement in physical activity and readiness to change among adolescents with chronic pain.

INTRODUCTION: Engaging adolescents with chronic pain in physical activities is challenging. Motivational interviewing (MI) combined with activity promotion may encourage teens to make behavioural changes. This research aimed to assess the feasibility and acceptability of our MI-based physical activity promotion programme, the M3 training. METHODS: In our exploratory study with 35 adolescent-parent dyads, we evaluated the feasibility by enrolment, drop-out and retention rates. Acceptability of the M3 training was examined by adherence rates and participation experiences through open-ended questions. We also assessed changes in pain self-efficacy and readiness to change after the M3 training intervention. RESULTS: The M3 training was feasible with an adequate enrolment (77.8%) and retention (85.7%) rate. Both teens and parents found the M3 training acceptable and considered exercise and physical activity the most helpful elements of the programme (36% and 37%, respectively). While self-efficacy remained unchanged, we identified a significant increase in the readiness to change for adolescents and parents. CONCLUSION: M3 training improved physical activity engagement while prioritising adolescents' autonomy. Furthermore, it appears to be a clinically relevant approach and could result in a positive shift in readiness to change within a shorter timeframe. PATIENT OR PUBLIC CONTRIBUTION: The preliminary version of the M3 training was reviewed and commented upon by the public (adolescents and adults). Adolescents who participated in this study were designing their own movement programme, considering their lived experiences. Participants' feedback was used to create the online version of the M3 training (which will be published elsewhere).

Characterisation of antibiotic resistance, virulence, clonality and mortality in MRSA and MSSA bloodstream infections at a tertiary-level hospital in Hungary: a 6-year retrospective study.

BACKGROUND: Staphylococcus aureus bloodstream infections (BSI) cause significant morbidity and mortality due to the frequent antibiotic resistance, toxin and adhesin production of the bacterium. These characteristics differ significantly in methicillin resistant (MRSA) and methicillin sensitive S. aureus (MSSA) and also among isolates of different MRSA clones, contributing to the outcome of S. aureus bacteraemia. METHODS: In this study, all MRSA BSI isolates from Semmelweis University, Budapest, Hungary, isolated between 2011-2016 and the same number of matched MSSA (overall 306 isolates) were characterised in terms of antibiotic susceptibility, virulence genes, clonality and their association with all-cause 30-day mortality. Effect of patient related variables, such as age, gender and comorbidities were also investigated. RESULTS: ST22-MRSA-IV and ST5-MRSA-II were the most prevalent clones in our study. SCCmec I isolates showed the highest resistance rates and SCCmec II carried most virulence genes. Infections caused by SCCmec IV isolates were associated with the highest mortality rate (42.2%), despite the similar comorbidity rates of the different patient groups. All-cause 30-day mortality was 39.9% in the MRSA and 30.7% in the MSSA group. Increased teicoplanin MIC was associated with high mortality rate. Resistance to ciprofloxacin, erythromycin and clindamycin was common in MRSA, whereas MSSA isolates were more sensitive to all antibiotics with the exception of doxycycline. All MRSA isolates were sensitive to glycopeptides and linezolid; resistance to rifampicin and sulfamethoxazole-trimethoprim was low. MRSA isolates carried more adhesion genes, superantigens were more frequent in MSSA. Panton-Valentine leukocidin was found in 2.3% of the isolates. CONCLUSION: This study provides insight into the clonal composition and associated mortality of BSI S. aureus isolates in Hungary. The results suggest that the outcome of the infection is determined by the antibiotic resistance, genotype of the bacterium, and patient-related factors; rather than the virulence factors carried by the bacteria.

Ceftazidime-avibactam and ceftolozane-tazobactam susceptibility of multidrug resistant Pseudomonas aeruginosa strains in Hungary.

Our objective was to compare the activity ceftazidime-avibactam (C/A) and ceftolozane-tazobactam (C/T) against multidrug (including carbapenem) resistant Pseudomonas aeruginosa clinical isolates collected from six diagnostic centers in Hungary and to reveal the genetic background of their carbapenem resistance. Two hundred and fifty consecutive, non-duplicate, carbapenem-resistant multidrug resistant (MDR) P. aeruginosa isolates were collected in 2017. Minimal inhibitory concentration values of ceftazidime, cefepime, piperacillin/tazobactam, C/A and C/T were determined by broth microdilution method and gradient diffusion test. Carbapenem inactivation method (CIM) test was performed on all isolates. Carbapenemase-encoding blaVIM, blaIMP, blaKPC, blaOXA-48-like and blaNDM genes were identified by multiplex PCR. Of the isolates tested, 33.6% and 32.4% showed resistance to C/A and C/T, respectively. According to the CIM test results, 26% of the isolates were classified as carbapenemase producers. The susceptibility of P. aeruginosa isolates to C/A and C/T without carbapenemase production was 89% and 91%, respectively. Of the CIM-positive isolates, 80% were positive for blaVIM and 11% for blaNDM. The prevalence of Verona integron-encoded metallo-beta-lactamase (VIM)-type carbapenemase was 20.8%. NDM was present in 2.8% of the isolates. Although the rate of carbapenemase-producing P. aeruginosa strains is high, a negative CIM result indicates that either C/A or C/T could be effective even if carbapenem resistance has been observed.

Similar Strains of Coagulase-Negative Staphylococci Found in the Gastrointestinal Tract and Bloodstream of Bacteremic Neonates.

OBJECTIVES: Premature neonates are susceptible to opportunistic and nosocomial infections. Efforts have been made to determine whether the neonatal gut microbiome possesses potential for causing bloodstream infections in newborns via microbial translocation from the gastrointestinal tract. We aimed to examine similarities in coagulase-negative staphylococci (CoNS) strains found in the gastrointestinal tract and bloodstream in bacteremic neonates. METHODS: CoNS strains isolated from blood cultures and perianal and pharyngeal swab samples of neonates from two neonatal intensive care units were investigated using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and pulsed-field gel electrophoresis. Molecular mass and genetic similarities of CoNS strains were compared. RESULTS: Marked similarity was found in the molecular mass and genetic profile of examined CoNS isolates from blood cultures and perianal/pharyngeal samples. The percentage of neonates developing bacteremia following perianal and pharyngeal colonization by CoNS was significantly higher when compared to those colonized by Enterobacteriales species (p < 0.0002). CONCLUSIONS: CoNS colonizing the gut may be a source of bacteremia in neonates. Enterobacteriales species do not contribute as significantly to bacteremia when compared to CoNS, and may be protective against gut mucosa-originated systemic infection.

High prevalence of group B streptococcus ST17 hypervirulent clone among non-pregnant patients from a Hungarian venereology clinic.

BACKGROUND: Although Streptococcus agalactiae is the leading causative agent of neonatal sepsis and meningitis, recently it is increasingly isolated from non-pregnant adults. The relation between its presence in the genitourinary tract and manifested clinical symptoms of STD patients remains an open question. In this study, a complex epidemiological investigation of GBS isolates from a venerology clinic was performed. METHODS: Ninety-six GBS isolates were serotyped and their genetic relatedness determined by PFGE. MLST was also performed for a subset of 20 isolates. The antibiotic susceptibility was tested with agar dilution. Surface proteins and the ST-17 hypervirulent clone was detected by PCR. RESULTS: The serotype prevalence was the following: V (29.2%), III (27.1%), Ia (22.9%), IV (10.4%), II (5.2%) and Ib (4.2%). A strong association was demonstrated between surface protein genes and serotypes. All isolates were fully susceptible to penicillin, but erythromycin and clindamycin resistance was high (41.7 and 35.4%, respectively), and 8 phenotypically macrolide sensitive isolates carried the ermB gene. 21.9% of all strains belonged to the hypervirulent ST17 clone, most being of serotype III and all were rib +. We found a few serotype IV isolates belonging to several STs and one serotype V/ST110 strain, containing a 44-bp deletion in the atr allele. CONCLUSIONS: The presence of silent ermB genes is of worry, as their expression upon macrolide exposure could lead to unforeseen therapeutic failure, while clindamycin is used for intrapartum antibiotic prophylaxis, in case of penicillin allergy. The other alarming result is the high prevalence of ST17 among these strains from STD patients, who could be sources of further infections. This is the first report from Hungary providing both serotyping and genotyping data of GBS isolates. These results could be helpful for vaccine production as the major vaccine candidates are capsular antigens or surface proteins.

Contribution of OqxAB Efflux Pump in Selection of Fluoroquinolone-Resistant Klebsiella pneumoniae.

The role of OqxAB efflux pump in Klebsiella pneumoniae was investigated in correlation with ciprofloxacin exposure. K. pneumoniae SE23 and K. pneumoniae SE191 were isolated from urinary tract infections and were analyzed in this study. Each carried oqxAB resistance determinant and exhibited ciprofloxacin MIC of 0.06 and 0.5 mg/L, respectively. Tested strains were initially exposed to their ciprofloxacin MIC values for 24 hours. Later on, the ciprofloxacin exposition has been increased to a daily 1, 2, 4, and to a final 8 mg/L. Total cellular RNA was extracted at 30, 60, 90, and 120 minutes of initial exposure and after every 24 hours. Quantitative reverse-transcriptase PCR was performed from each RNA sample. Mutation in gyrA and parC genes was analyzed in each strain and multilocus sequence typing (MLST) was performed. Ciprofloxacin exposure selected resistant strain from K. pneumoniae SE191; by contrast, K. pneumoniae SE23 was not adjustable to the increasing ciprofloxacin concentrations. During initial exposure, both oqxA and oqxB expression remained low (2-ΔCt = 1-2.03). However, increasing ciprofloxacin promoted oqxB expression as it reached fold increase of 15.8-22.8, while oqxA expression was maintained (2-ΔCt = 2-2.15). An amino acid substitution Ser83Tyr in gyrA was detected in K. pneumoniae SE191, but no additional mutations occurred as consequence to ciprofloxacin exposure. MLST identified K. pneumoniae SE191 as ST274, while K. pneumoniae SE23 belonged to the novel ST2567. Ciprofloxacin concentration-dependent upregulation of oqxAB efflux pump in K. pneumoniae is clonally related and contributes to selection for higher level of fluoroquinolone resistance.

[Uncommon non-fermenting Gram-negative rods as pathogens of lower respiratory tract infection]. / Ritkábban eloforduló, alsó légúti fertozést okozó Gram-negatív nem fermentáló pálcák.

INTRODUCTION: Glucose non-fermenting Gram-negative bacteria are ubiquitous environmental organisms. Most of them are identified as opportunistic, nosocomial pathogens in patients. Uncommon species are identified accurately, mainly due to the introduction of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) in clinical microbiology practice. Most of these uncommon non-fermenting rods are isolated from lower respiratory tract samples. Their significance in lower respiratory tract infections, such as rules of their testing are not clarified yet. AIM: The aim of this study was to review the clinical microbiological features of these bacteria, especially their roles in lower respiratory tract infections and antibiotic treatment options. METHOD: Lower respiratory tract samples of 3589 patients collected in a four-year period (2013-2016) were analyzed retrospectively at Semmelweis University (Budapest, Hungary). Identification of bacteria was performed by MALDI-TOF MS, the antibiotic susceptibility was tested by disk diffusion method. RESULTS: Stenotrophomonas maltophilia was revealed to be the second, whereas Acinetobacter baumannii the third most common non-fermenting rod in lower respiratory tract samples, behind the most common Pseudomonas aeruginosa. The total number of uncommon non-fermenting Gram-negative isolates was 742. Twenty-three percent of isolates were Achromobacter xylosoxidans. Beside Chryseobacterium, Rhizobium, Delftia, Elizabethkingia, Ralstonia and Ochrobactrum species, and few other uncommon species were identified among our isolates. The accurate identification of this species is obligatory, while most of them show intrinsic resistance to aminoglycosides. Resistance to ceftazidime, cefepime, piperacillin-tazobactam and carbapenems was frequently observed also. CONCLUSIONS: Ciprofloxacin, levofloxacin and trimethoprim-sulfamethoxazole were found to be the most effective antibiotic agents. Orv Hetil. 2018; 159(1): 23-30.

First description of a catalase-negative Staphylococcus aureus from a healthy carrier, with a novel nonsense mutation in the katA gene.

We have screened 2568 healthy individuals (mostly children) for Staphylococcus aureus and Streptococcus pneumoniae nasal carriage between 2010 and 2012. Out of the isolated 751 S. aureus strains, we found one methicillin-sensitive catalase-negative S. aureus (CNSA). Our CNSA isolate possessed a novel nonsense point mutation in the katA gene leading to early truncation of the protein product. The strain was resistant to penicillin and erythromycin, but sensitive to all other tested antibiotics and carried the enterotoxin A gene. It belonged to sequence type 5 (ST5), which is a successful, worldwide spread, usually MRSA clone. Catalase has been described as a virulence factor strictly required for nasal colonisation, and this is the first case contradicting this theory, as all previous CNSA isolates derived from infections. This is the first report of a CNSA from a symptomless carrier as well as the first occurrence in Hungary.

[Relationship of consequences of anastomotic insufficiency and bacterial flora of oral cavity in patients with esophageal and cardia cancer]. / A szájüreg baktériumflórájának összefüggése az anastomosiselégtelenség következményeivel nyelocso- és cardiatumoros betegeknél.

INTRODUCTION: In the course of anastomotic insufficiency following resection of esophageal cancers the bacterial compound of the esophageal substance has a remarkable, presumable role in the outcome of complications. AIM: The purpose of this study is to compare the consequences of the anastomotic leak with the bacterial flora of patients' oral cavity. METHOD: In this prospective study a total of 131 patients were investigated directly before the surgical intervention taking a bacterial sample. Bacterial flora of patients' oral cavity was analysed; and the correlation between the consequences of the anastomotic leak and the content of the bacterial flora was examined. RESULTS: Pathogenic bacteria in the oral microflora in 50 cases (38.2%) was found. Statistically significant, moderate correlation was found between the severity of the complication and the incidence of pathogenic bacteria (rs = 0.553; p≤0.05). CONCLUSIONS: Pathogenic agent in the microbial flora might induce higher risk and more severe outcome in case of anastomotic leakage and it might be evaluated as a determinative factor. Consideration of the bacterial flora of the oral cavity requires more attention in the preoperative preparation than before and it demands the change of the current practice. Orv. Hetil., 2017, 158(1), 25-30.

[Periprosthetic joint infection caused by Rhodococcus equi. Case report]. / Rhodococcus equi által okozott nagyízületi endoprotézis körül kialakult fertozés.

Rhodococcus equi is a rare pathogen in humans causing infections mostly in immunocompromised hosts. We present the first case of periprosthetic joint infection caused by Rhodococcus equi. An 88-year-old male patient was referred to our clinic with a history of fever and right hip pain. The patient had multiple hip surgeries including total joint arthroplasty and revision for aseptic loosening on the right side. He was immunocompetent, but his additional medical history was remarkable for diabetes mellitus, diabetic nephropathy and stroke with hemiplegia resulting in immobilization. Radiography showed stable components, joint aspirate yielded Rhodococcus equi. Irrigation and debridement was proposed, but the patient refused any surgical intervention. Therefore antibiotic therapy was administered. At the last follow-up the patient is free of complaints but the C-reactive protein level is still elevated. This case illustrates the possible role of Rhodococcus equi in medical device-associated infections. Orv Hetil. 2017; 158(27): 1071-1074.

Infection and colonization by Stenotrophomonas maltophilia: antimicrobial susceptibility and clinical background of strains isolated at a tertiary care centre in Hungary.

BACKGROUND: Stenotrophomonas maltophilia is an important opportunistic, mainly nosocomial pathogen that emerged in the last decades worldwide. Due to its inherent extended antibiotic resistance, therapeutic options are strongly limited. New resistance mechanisms in S. maltophilia make antibiotic therapy even more difficult. The aim of our study was to investigate the antimicrobial resistance of S. maltophilia isolates collected in our laboratory and to reveal related clinical background. METHOD: Consecutive non-duplicate S. maltophilia isolates (n = 160) were collected in a three-year period. Conventional methods, automated identification system and MALDI-TOF MS was used for identification, ERIC-PCR for genetic relationship analysis and broth microdilution method to determine the susceptibility for trimethoprim/sulfamethoxazole (SXT), ciprofloxacin, levofloxacin, moxifloxacin, colistin, doxycycline and tigecycline. Clinical final reports were used retrospectively to collect clinical information. RESULTS: ERIC-PCR revealed large heterogeneity. Trimethoprim/sulfamethoxazole, moxifloxacin and levofloxacin were found to be the most effective agents with MIC50/MIC90 0.5/1, 0.25/1, 1/2 mg/l, respectively. Seventy percent of patients with S. maltophilia infection were treated in intensive care units. All-cause mortality rate was 45%. Nearly 70% of the isolates were collected from polymicrobial infections/colonizations. CONCLUSIONS: Trimethoprim/sulfamethoxazole is the most potent antibiotic agent against S. maltophilia. In case of SXT hypersensitivity, intolerance or resistance, fluoroquinolones are alternative therapeutic options. Missing clinical breakpoints, consensus antibiotic susceptibility testing guidelines and clinical trials make the interpretation of antibiotic susceptibility testing results difficult. The indirect pathogenicity of S. maltophilia in polymicrobial infections or colonizations has to be taken into consideration.

[Special application of matrix-assisted laser desorption ionization time-of-flight mass spectrometry in clinical microbiological diagnostics]. / Mátrix-asszisztált lézer deszorpciós, ionizációs, repülési ido mérésén alapuló tömegspektrometria speciális alkalmazása a klinikai mikrobiológiai diagnosztika területén.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry as a new possibility for rapid identification of bacteria and fungi revolutionized the clinical microbiological diagnostics. It has an extreme importance in the routine microbiological laboratories, as identification of the pathogenic species rapidly will influence antibiotic selection before the final determination of antibiotic resistance of the isolate. The classical methods for identification of bacteria or fungi, based on biochemical tests, are influenced by many environmental factors. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry is a rapid method which is able to identify a great variety of the isolated bacteria and fungi based on the composition of conserved ribosomal proteins. Recently several other applications of the method have also been investigated such as direct identification of pathogens from the positive blood cultures. There are possibilities to identify bacteria from the urine samples in urinary tract infection or from other sterile body fluids. Using selective enrichment broth Salmonella sp from the stool samples can be identified more rapidly, too. The extended spectrum beta-lactamase or carbapenemase production of the isolated bacteria can be also detected by this method helping the antibiotic selection in some cases. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry based methods are suitable to investigate changes in deoxyribonucleic acid or ribonucleic acid, to carry out rapid antibiotic resistance determination or other proteomic analysis. The aim of this paper is to give an overview about present possibilities of using this technique in the clinical microbiological routine procedures.

Vaccine Effectiveness against GP-Attended Symptomatic COVID-19 and Hybrid Immunity among Adults in Hungary during the 2022-2023 Respiratory Season Dominated by Different SARS-CoV-2 Omicron Subvariants.

Hungary provides the opportunity to evaluate the effectiveness of COVID-19 vaccination in a setting where naturally acquired immunity and hybrid immunity are likely to play a greater role due to suboptimal vaccination coverage. METHODS: A test-negative study was conducted during the 2022-2023 respiratory season at the primary care level to determine the effectiveness of at least one COVID-19 booster dose in preventing medically attended symptomatic RT-PCR-confirmed SARS-CoV-2 infection in adults. Unvaccinated patients were used as a reference group. RESULTS: A total of 247 cases and 1073 controls were included in the analysis. CVE was 56.8% (95% CI: 11.9-78.8%) in the population aged 60 years and older and 2.3% (95% CI: -50.0-36.3%) in the younger adults against COVID-19 caused by Omicron subvariants, mainly BA.5, BQ.1, and XBB.1. Self-reported COVID-19 in the 60-365 days prior to the current illness did not confer protection against reinfection without vaccination, but together with booster vaccination, it reduced the risk of COVID-19 by 63.0% (95% CI: -28.0-89.3%) and 87.6% (95% CI: 26.4-97.9%) among the 18-59 and 60+ age groups, respectively. CONCLUSIONS: CVE against COVID-19 was moderately high in the 60+ age groups. Because of the benefit of hybrid immunity, persons with previous SARS-CoV-2 infection should still be considered for vaccination campaigns.

Prevalence, serogroup distribution and risk factors of Neisseria meningitidis carriage in high school and university students in Hungary.

Neisseria meningitidis causes life-threatening invasive meningococcal disease (IMD) with high mortality worldwide. Asymptomatic pharyngeal meningococcus colonisation is an important reservoir for the spread of the bacterium. The aim of this study was to determine N. meningitidis colonisation rates in asymptomatic high school and university students and to identify risk factors for carriage. Oropharyngeal swab samples and data from a self-reported questionnaire were obtained from overall 610 students, among them 303 university students and 307 high school students, aged between 15 and 31 years in Budapest, Hungary, between November 2017 and December 2018. Meningococcal carriage and serogroup of N. meningitidis were determined by RT-PCR from DNA extracted directly from the specimen. N. meningitidis was identified in 212 (34.8 %) of the participants. Significantly higher carriage rate was found among high school students (48.9 %) compared to university students (20.5 %). Peak of colonisation rate was among 17-19-year-old students (48.7 %). Most carriage isolates were non-typable (87.3 %). From the 212 meningococcus carriers, 19 were colonised by serogroup B (9 %), 5 by serogroup C (2.4 %), and 1 had serogroup Y (0.5 %). Significantly higher colonisation rate was found among males (42.4 %) than in females (33.1 %). Antibiotic use in the past 2 months has decreased the rate of meningococcal colonisation. Recent respiratory infection, active or passive smoking and attending parties have not influenced meningococcal colonisation rate significantly. In conclusion, we have found high asymptomatic meningococcus carriage rate among high school students and young adults, however, the majority of the colonizing meningococci were non-typable.

The effect of COVID-19 vaccination status on all-cause mortality in patients hospitalised with COVID-19 in Hungary during the delta wave of the pandemic.

The high mortality of patients with coronavirus disease 2019 (COVID-19) is effectively reduced by vaccination. However, the effect of vaccination on mortality among hospitalised patients is under-researched. Thus, we investigated the effect of a full primary or an additional booster vaccination on in-hospital mortality among patients hospitalised with COVID-19 during the delta wave of the pandemic. This retrospective cohort included all patients (n = 430) admitted with COVID-19 at Semmelweis University Department of Medicine and Oncology in 01/OCT/2021-15/DEC/2021. Logistic regression models were built with COVID-19-associated in-hospital/30 day-mortality as outcome with hierarchical entry of predictors of vaccination, vaccination status, measures of disease severity, and chronic comorbidities. Deceased COVID-19 patients were older and presented more frequently with cardiac complications, chronic kidney disease, and active malignancy, as well as higher levels of inflammatory markers, serum creatinine, and lower albumin compared to surviving patients (all p < 0.05). However, the rates of vaccination were similar (52-55%) in both groups. Based on the fully adjusted model, there was a linear decrease of mortality from no/incomplete vaccination (ref) through full primary (OR 0.69, 95% CI: 0.39-1.23) to booster vaccination (OR 0.31, 95% CI 0.13-0.72, p = 0.006). Although unadjusted mortality was similar among vaccinated and unvaccinated patients, this was explained by differences in comorbidities and disease severity. In adjusted models, a full primary and especially a booster vaccination improved survival of patients hospitalised with COVID-19 during the delta wave of the pandemic. Our findings may improve the quality of patient provider discussions at the time of admission.

Vaccine effectiveness against influenza hospitalisation in adults during the 2022/2023 mixed season of influenza A(H1N1)pdm09, A(H3N2) and B circulation, Europe: VEBIS SARI VE hospital network.

We conducted a multicentre hospital-based test-negative case-control study to measure vaccine effectiveness (VE) against PCR-confirmed influenza in adult patients with severe acute respiratory infection (SARI) during the 2022/2023 influenza season in Europe. Among 5547 SARI patients ≥18 years, 2963 (53%) were vaccinated against influenza. Overall VE against influenza A(H1N1)pdm09 was 11% (95% CI: -23-36); 20% (95% CI: -4-39) against A(H3N2) and 56% (95% CI: 22-75) against B. During the 2022/2023 season, while VE against hospitalisation with influenza B was >55%, it was ≤20% for influenza A subtypes. While influenza vaccination should be a priority for future seasons, improved vaccines against influenza are needed.

Enterobacterales carrying chromosomal AmpC ß-lactamases in Europe (EuESCPM): Epidemiology and antimicrobial resistance burden from a cohort of 27 hospitals, 2020-2022.

INTRODUCTION: The ESCPM group (Enterobacter species including Klebsiella aerogenes - formerly Enterobacter aerogenes, Serratia species, Citrobacter freundii complex, Providencia species and Morganella morganii) has not yet been incorporated into systematic surveillance programs. METHODS: We conducted a multicentre retrospective observational study analysing all ESCPM strains isolated from blood cultures in 27 European hospitals over a 3-year period (2020-2022). Diagnostic approach, epidemiology, and antimicrobial susceptibility were investigated. RESULTS: Our study comprised 6,774 ESCPM isolates. MALDI-TOF coupled to mass spectrometry was the predominant technique for bacterial identification. Susceptibility to new ß-lactam/ß-lactamase inhibitor combinations and confirmation of AmpC overproduction were routinely tested in 33.3% and 29.6% of the centres, respectively. The most prevalent species were E. cloacae complex (44.8%) and S. marcescens (22.7%). Overall, third-generation cephalosporins (3GC), combined third- and fourth-generation cephalosporins (3GC + 4GC) and carbapenems resistance phenotypes were observed in 15.7%, 4.6%, and 9.5% of the isolates, respectively. AmpC overproduction was the most prevalent resistance mechanism detected (15.8%). Among carbapenemase-producers, carbapenemase type was provided in 44.4% of the isolates, VIM- (22.9%) and OXA-48-enzyme (16%) being the most frequently detected. E. cloacae complex, K. aerogenes and Providencia species exhibited the most notable cumulative antimicrobial resistance profiles, with the former displaying 3GC, combined 3GC + 4GC and carbapenems resistance phenotypes in 15.2%, 7.4%, and 12.8% of the isolates, respectively. K. aerogenes showed the highest rate of both 3GC resistant phenotype (29.8%) and AmpC overproduction (32.1%), while Providencia species those of both carbapenems resistance phenotype (42.7%) and carbapenemase production (29.4%). ESCPM isolates exhibiting both 3GC and combined 3GC + 4GC resistance phenotypes displayed high susceptibility to ceftazidime/avibactam (98.2% and 95.7%, respectively) and colistin (90.3% and 90.7%, respectively). Colistin emerged as the most active drug against ESCPM species (except those intrinsically resistant) displaying both carbapenems resistance phenotype (85.8%) and carbapenemase production (97.8%). CONCLUSIONS: This study presented a current analysis of ESCPM species epidemiology in Europe, providing insights to inform current antibiotic treatments and guide strategies for antimicrobial stewardship and diagnostics.

Specific nasopharyngeal Corynebacterium strains serve as gatekeepers against SARS-CoV-2 infection.

The SARS-CoV-2 virus is still causing a worldwide problem. The virus settles primarily on the nasal mucosa, and the infection and its course depend on individual susceptibility. Our aim was to investigate the nasopharynx composition's role in the individual susceptibility. During the first phase of SARS-CoV-2 pandemic, nasopharyngeal microbiome samples of close contact unvaccinated patients were investigated by 16S rRNA analysis and by culturing. The whole genome of cultured Corynebacteria was sequenced. The relative expression of ACE2, TMPRSS2, and cathepsin L on Caco-2 cells and the strength of S1-ACE2 binding were determined in the presence of Corynebacteria. From 55 close contacts exposed to identical SARS-CoV-2 exposure, 26 patients became infected and 29 remained uninfected. The nasopharyngeal microbiome analysis showed significantly higher abundance of Corynebacteria in uninfected group. Corynebacterium accolens could be cultivated only from uninfected individuals and Corynebacterium propinquum from both infected and uninfected. Corynebacteria from uninfected patient significantly reduced the ACE2 and cathepsin L expression. C. accolens significantly reduced the TMPRSS2 expression compared to other Corynebacteria. Furthermore, Corynebacterium spp. weakened the binding of the S1-ACE2. Most C. accolens isolates harbored the TAG lipase LipS1 gene. Based on these results, the presence of Corynebacterium spp. in the nasopharyngeal microbiota, especially C. accolens strains, could reduce the individual susceptibility to SARS-CoV-2 infection by several mechanisms: by downregulation the ACE2, the TMPRSS2 receptors, and cathepsin L in the host; through the inhibition of S1-ACE2 binding; and lipase production. These results suggest the use of C. accolens strains as probiotics in the nasopharynx in the future.

Coagulase-negative staphylococcal endophthalmitis: clinical severity and outcomes based on speciation.

OBJECTIVE: To identify characteristics and visual outcomes of coagulase-negative staphylococcal (CoNS) endophthalmitis in the era after the Endophthalmitis Vitrectomy Study. DESIGN: Single-centre retrospective analysis. PARTICIPANTS: Forty-two samples from 40 patients with documented CoNS endophthalmitis. METHODS: Visual acuity outcomes of CoNS endophthalmitis were assessed in relation to species and type of treatment instituted (i.e., pars plana vitrectomy [PPV] versus vitreous tap and injection of intravitreal antibiotics [T&I]) on 42 samples from 40 patients. RESULTS: Staphylococcus epidermidis was the most prevalent CoNS in our study. Cataract surgery and intravitreal injections were the most common sources for acute CoNS endophthalmitis. Eyes presenting with hand motion or better vision had similar mean final vision after either intravitreal antibiotics or PPV, whereas those with light perception or worse vision at onset had better outcomes after PPV only. Subanalysis showed that patients with S. epidermidis endophthalmitis (n = 39 eyes) had similar visual outcomes with either intravitreal injections or PPV regardless of visual acuity. Hypopyon and vitritis are not always present. CONCLUSIONS: Patients with S. epidermidis endophthalmitis may benefit similarly from either early vitrectomy or intravitreal antibiotic injections regardless of visual acuity. This finding may be a supplement to the complements the management standards set forth by the Endophthalmitis Vitrectomy Study.