Characteristics of Enterococcus species bloodstream infections among adults with and without onco-hematological malignancies: Experiences from the national center of Hungary.

Introduction: Over the past decade, enterococcal bloodstream infection (BSI) shows increasing incidence globally among the elderly and in patients with comorbidities. In this study, we aimed to assess microbiological and clinical characteristics and long-term outcomes of BSIs caused by Enterococcus spp. in adult patients with and without active onco-hematological malignancies hospitalized at a national referral institute. Methods: A prospective analysis of consecutive enterococcal BSI cases was conducted in the National Institute of Hematology and Infectious Diseases (Budapest, Hungary) between December 2019 and April 2022. We compared characteristics and outcomes at 30-days and 1 year after diagnosis among patients with and without onco-hematological malignancies. Results: In total, 141 patients were included (median age 68 ± 21 years, female sex 36.9%), 37% (52/141) had active onco-hematological malignancies. The distribution of species was as follows: 50.4% Enterococcus faecalis, 46.1% Enterococcus faecium, 1.4% Enterococcus avium and Enterococcus gallinarum, and 0.7% Enterococcus raffinosus. No statistically significant differences in all-cause mortality rates were observed between patient subgroups at 30 days (32.7 vs. 28.1%; P = 0.57) and 1 year (75.0 vs. 60.7%; P = 0.09). Conclusion: Enterococcal bloodstream infections yielded a relevant burden of morbidity, but with no statistical difference in long-term outcomes of adult patients with and without active onco-hematological malignancies.

Antibody and T Cell Responses against SARS-CoV-2 Elicited by the Third Dose of BBIBP-CorV (Sinopharm) and BNT162b2 (Pfizer-BioNTech) Vaccines Using a Homologous or Heterologous Booster Vaccination Strategy.

In the present study, antibody and T cell-mediated immune responses elicited by BBIBP-CorV and BNT162b2 vaccines were compared 6 months after the two-dose immunization of healthy individuals. Additionally, antibody and T cell responses after the third dose of BBIBP-CorV or BNT162b2 were compared using a homologous or heterologous vaccination strategy. The third dose was consistently administered 6 months after the second dose. Six months following the two-dose vaccination, the cumulative IFNγ-positive T cell response was almost identical in participants immunized with either two doses of BNT162b2 or BBIBP-CorV vaccines; however, significant differences were revealed regarding humoral immunity: the two-dose BNT162b2 vaccine maintained a significantly higher antireceptor-binding domain (RBD) IgG, anti-spike (S1/S2) IgG, and IgA antibody levels. The BNT162b2 + BNT162b2 + BBIBP-CorV vaccine series elicited significantly lower anti-RBD IgG and anti-S1/S2 IgG levels than three doses of BNT162b2, while the anti-S IgA level was equally negligible in both groups. Importantly, the cumulative IFNγ-positive T cell response was highly similar in both groups. Surprisingly, the BBIBP-CorV + BBIBP-CorV + BNT162b2 vaccination series provided a much higher cumulative IFNγ-positive T cell response than that elicited by three doses of BNT162b2; moreover, the levels of anti-RBD IgG and anti-S IgA were almost identical. Only the mean anti-S1/S2 IgG levels were higher after receiving three mRNA vaccines. Based on these data, we can conclude that administering a third dose of BNT162b2 after two doses of BBIBP-CorV is an effective strategy to significantly enhance both humoral and T cell-mediated immune response, and its effectiveness is comparable to that of three BNT162b2 vaccines.

Immunologic complications of infections: the relevance of the grey zone / Fertozésekhez kapcsolódó immunológiai jelenségek: a szürkezóna jelentosége.

Összefoglaló. A fertozésekhez kapcsolódó immunológiai kórképekre különösen jellemzo, hogy mind etiológiai tényezoikben, mind klinikai képükben rendkívül heterogének. Az átfedo és inkomplett megjelenési formák nem ritkák, ami a diagnosztika standardizálását nehezíti. Egyes, a fertozésekhez opcionálisan kapcsolódó tünetek megfigyelése már több mint egy évszázaddal ezelott elvezetett a gócelmélet megszületéséhez, amely eredeti formájában leginkább elnagyolt és naiv feltételezéseken alapult. Folyamatosan bovülo ismereteink ugyanakkor egyre több esetben támasztják alá, hogy az átvészelt, esetleg krónikus vagy perzisztáló fertozések, illetve a mikrobiom összetétele számos ponton lehet befolyással immunológiai, metabolikus és endokrin homeosztázisunkra. A jelen munkában az ismert összefüggéseket, illetve a meghaladott feltételezéseket is röviden érintve megkíséreljük a rendelkezésre álló ismereteken keresztül áttekinteni a fertozésekhez kapcsolódó immunológiai jelenségek szürkezónáját, azon kórtani folyamatokat és tüneteket, amelyek létezése igazolható, de terápiás következményeik az egyén szintjén egyelore bizonytalanok. Orv Hetil. 2021; 162(38): 1526-1532. Summary. Immunologic phenomena related to infections are well known to be truly heterogeneous, both regarding their etiology and the clinical picture. Overlapping symptoms and incomplete presentations are not seldom, which often constitute diagnostic challenge. Certain, optional complications of infectious diseases led to the creation of the focal infection theory more than a century ago, although only on the basis of assumptions derived from elusive and naive theories. However, an expanding body of evidence ever since did underline the impact of previous and persistent infections on the immunologic, metabolic and endocrine homeostasis. Besides briefly touching the well-defined diseases, as well as the outdated theories of this field, we aim to provide an overview of the grey zone of infection-related immunologic phenomena, the existence of which is biologically well established, however, their true significance on an individual basis remains uncertain. Orv Hetil. 2021; 162(38): 1526-1532.

The potential impact of Helicobacter pylori seropositivity on recombinant antigen-based Lyme serology.

We assessed the impact of Helicobacter pylori seropositivity on recombinant antigen-based Lyme serology. We compared the IgG ELISA+LIA (line immunoassay) reactivity of anti-Helicobacter IgG positive and negative samples. The ELISA S/Co values and LIA band numbers were identical. Our results suggest that Helicobacter seropositivity lacks an apparent effect on Lyme disease test reactivity.

Characteristics and predictors of treatment failure with intravenous tigecycline monotherapy among adult patients with severe Clostridioides (Clostridium) difficile infection: a single-centre observational cohort study.

Our aim was to analyze characteristics of treatment failure with intravenous tigecycline monotherapy among adults with severe Clostridioides (Clostridium) difficile infection (CDI). A single-centre observational cohort study was performed between 2014 and 2018. Data were collected by charts review, diagnosis and severity were determined by ESCMID guidelines. Primary outcome was treatment failure, secondary outcomes were in-hospital mortality, relapse, colectomy, and complication rates. Independent predictors of failure were identified using logistic regression. Altogether 110 patients were included, failure occurred in 37.3%. Patients with failure frequently had chronic heart and pulmonary co-morbidities, peritonitis, higher CRP levels, ICU admittance rates and need for total parenteral nutrition and vasopressors. Mostly, CDI-specific mortality and complications contributed to failure. Relapse rates were similar. Chronic pulmonary disease, ileus, total parenteral nutrition, and duration of tigecycline therapy were predictors of failure. We conclude that severe CDI cases with higher risk for tigecycline monotherapy failure might be identified by contributing factors.

["Tempus fugit, venit mors" - about streptococcal toxic shock syndrome: a case report and mini-review]. / "Tempus fugit, venit mors" ­ a streptococcalis toxikus sokk szindrómáról egy eset kapcsán.

Streptococcal toxic shock syndrome (STSS) is a hyperacute, life-threatening illness, a complication of invasive streptococcal (mostly group A, rarely groups B, G or C) infection. There is no portal of entry (skin, vagina, pharynx) in nearly half of the STSS cases. The initial signs and symptoms (fever, flu-like complaints, hypotension) are scarce and aspecific, but because of its rapid progression and poor prognosis, early high level of suspicion is necessary. Management has 3 crucial points: initiation of anti-streptococcal regimen (and intravenous immunoglobulin in some cases), aggressive intensive care support of multi-organ failure, and surgical control of the infective source. In this article, we present a case of a patient succumbing to streptococcal toxic shock syndrome which was preceded by primary S. pyogenes bacteremia, and review the key points of this potentially fatal disease for practising clinicians. Orv Hetil. 2019; 160(48): 1887-1893.

Colistin resistance associated with outer membrane protein change in Klebsiella pneumoniae and Enterobacter asburiae.

In this study, outer membrane proteins (OMPs) of colistin-resistant Klebsiella pneumoniae and Enterobacter asburiae were analyzed. One colistin-susceptible and three colistin-resistant K. pneumoniae sequence type 258 strains as well as one colistin-susceptible E. asburiae and its colistin-heteroresistant counterpart strain were involved in the study. OMP analysis of each strain was performed by microchip method. Matrix-assisted laser desorption ionization time of flight/mass spectrometry (MALDI-TOF/MS) investigation was carried out after separation of OMPs by two-dimensional gel electrophoresis and in-gel digestion. The MALDI-TOF/MS analysis of OMPs in the colistin-susceptible K. pneumoniae found 16 kDa proteins belonging to the LysM domain/BON superfamily, as well as DNA starvation proteins, whereas OmpX and OmpW were detected in the colistin-resistant counterpart strains. OmpC and OmpW were detected in the colistin-susceptible E. asburiae, whereas OmpA and OmpX were identified in the colistin-resistant counterpart. This study demonstrated that OMP differences were between colistin-susceptible and -resistant counterpart strains. The altered Gram-negative cell wall may contribute to acquired colistin resistance in Enterobacteriaceae.

MgrB variants in colistin-susceptible and colistin-resistant Klebsiella pneumoniae ST258.

Resistance determinants of a colistin susceptible and five colistin resistant Klebsiella pneumoniae ST258 from a Hungarian outbreak were investigated. A novel MgrB variant in colistin susceptible strain was found. Elevated phoP and arn gene expressions and wild-type PmrB in all colistin resistant K. pneumoniae were detected. All strains lacked mcr-1.

Effect of antimicrobial peptides on colistin-susceptible and colistin-resistant strains of Klebsiella pneumoniae and Enterobacter asburiae.

In this study susceptibility to different antimicrobial peptides was investigated on colistin-susceptible and colistin-resistant identical pulsotype strains of KPC-2 producing Klebsiella pneumoniae ST258 as well as colistin-susceptible and colistin-resistant Enterobacter asburiae strains isolated from clinical samples. In our test, bacteria were exposed to 50 mg/ml lactoferrin, lysozyme and protamine - cationic antimicrobial peptides belonging to innate immune system and having structural similarity to polymyxins - in separate reactions. After 18 hours incubation of colonies were counted. 40% of colistin-resistant K. pneumoniae strains and 97% of colistin-susceptible counterpart strains were lysed by protamine whereas 87% and 100% colony forming unit decrease by lysozyme was seen, respectively. In the case of colistin-resistant E. asburiae strains 1 log10 cell count increase were observed after treatment with lysozyme and 1.56 log10 after lactoferrin exposure compared to the initial number whereas the colistin-susceptible showed no relevant cell count increase. Our findings suggest that acquired colistin-resistance in Enterobacteriaceae is associated with tolerance against antimicrobial peptides.

[Thousand faces of Streptococcus pneumonia (pneumococcus) infections]. / A Streptococcus pneumoniae (pneumococcus) -infekciók ezer arca.

Incidence and mortality rates of infections caused by Streptococcus pneumoniae (pneumococcus) are high worldwide and in Hungary among paediatric as well as adult populations. Pneumococci account for 35-40% of community acquired adult pneumonias requiring hospitalization, while 25-30% of Streptococcus pneumoniae pneumonias are accompanied by bacteraemia. 5-7% of all infections are fatal but this rate is exponentially higher in high risk patients and elderly people. Mortality could reach 20% among patients with severe invasive pneumococcal infections. Complications may develop despite administration of adequate antibiotics. The authors summarize the epidemiology of pneumococcal infections, pathogenesis of non-invasive and invasive disease and present basic clinical aspects through demonstration of four cases. Early risk stratification, sampling of hemocultures, administration of antibiotics and wider application of active immunization could reduce the mortality of invasive disease. Anti-pneumococcal vaccination is advisable for adults of ≥50 years and high risk patients of ≥18 years who are susceptible to pneumococcal disease.

Synergistic antibiotic combinations for colistin-resistant Klebsiella pneumoniae.

In this study antibiotic combinations for multidrug-resistant Klebsiella pneumoniae strains were investigated. The study included a colistin-susceptible and a colistin-resistant KPC-2 producing K. pneumoniae ST258 strains isolated in 2008 and 2009 during an outbreak in Hungary. Antibiotic combinations were analyzed by checkerboard technique and fractional inhibitory concentration indices were calculated. The following antibiotics were tested: ceftazidime, cefotaxime, ceftriaxone, ampicillin, imipenem, ertapenem, amikacin, tobramycin, ciprofloxacin, levofloxacin, moxifloxacin, rifampicin, polymyxin B and colistin. Combinations including 0.25 µg/ml colistin plus 1 µg/ml rifampicin, 0.25 µg/ml polymyxin B plus 1 µg/ml rifampicin, 1 µg/ml imipenem plus 2 µg/ml tobramycin, were found synergistic.These in vitro synergistic combinations suggest potential therapeutical options against infections caused by KPC-2 producing, multidrug-resistant K. pneumoniae ST258.