Domagoj Drenjančević

Fatal fulminant sepsis due to a cat bite in an immunocompromised patient

ZusammenfassungDurch P. multocida ausgelöste Infektionen können sich beim Menschen als lokalisierte Infektionen des die Läsion umgebenden Bindegewebes, als Infektionen im Respirationstrakt oder als systemische Infektionen mit langsamer oder fulminanter Entwicklung präsentieren. Über 90% der humanen Infektionen sind Wundinfektionen oder Abszesse, die sich in Folge von Bissen, Kratzern oder Ablecken von Hautläsionen durch Hunde oder Katzen entwickelt haben. Schwere systemische Erkrankungen wie Pneumonie, Lungenabszess, Peritonitis, Endokarditis, Meningitis und Sepsis sind vor allem auch bei Patienten mit vorbestehenden Erkrankungen wohl bekannt. In der vorliegenden Arbeit berichten wir über einen immunkomprimittierten Patienten, der von einer ihm unbekannten Katze gebissen worden war, und der in sehr kurzer Zeit eine fulminante Sepsis entwickelte. Der Patient verstarb schließlich 70 Stunden nach dem Katzenbiss, trotz Intensivbehandlung und Reanimationsversuchen. Leider hatte er zu spät medizinische Hilfe aufgesucht. Wir möchten an Hand dieses Falles darauf hinweisen, dass es schon für die Erstversorgung wichtig ist, infektionsgefährdete Patienten besser über die Infektionsgefahr durch den Kontakt mit Tieren zu informieren. Sie sollten vor möglichen Konsequenzen von Verletzungen, auch durch eigene Haustiere, gewarnt werden.SummaryPasteurella multocida infections in humans can present as localized infections of soft tissues surrounding the lesions, as respiratory tract infections or as systemic infections with slow or fulminant development. Over 90% of human infections are cases of wound infections or abscesses related to a bite, scratch, or licking of skin lesions by a cat or dog. Severe systemic diseases such as pneumonia, lung abscess, peritonitis, endocarditis, meningitis and sepsis are also well known, especially in patients with underlying medical conditions. In this paper we report on an immunocompromised patient who was bitten by an unknown cat and very quickly developed fulminant sepsis, dying 70 hours after the cat bite, despite all the intensive care, therapy and reanimation he was given. Unfortunately, he asked for medical help too late. We emphasize the need for primary healthcare to provide more information to patients at risk of infections from contact with animals and to warn them about the possible consequences of injuries, even when the animals are pets.

Epidemic spread of OXA-48 beta-lactamase in Croatia

Purpose. A dramatic increase in OXA‐48 &bgr;‐lactamase was observed recently not only in large hospital centres, but also in smaller suburban hospital centres in geographic areas bordering Croatia. The aim of the study was to analyse the epidemiology, the mechanisms of antibiotic resistance and the routes of spread of OXA‐48 carbapenemase in Croatia. Methods. Carbapenemase and other &bgr;‐lactamase and fluoroquinolone resistance genes were detected by PCR and sequencing. Whole‐genome sequencing (WGS) was performed on five representative isolates. The isolates were genotyped by PFGE. Results. Forty‐eight isolates positive for OXA‐48, collected from seven hospital centres in Croatia from May 2016 to May 2017, were analysed (40 Klebsiella pneumoniae, 5 Enterobacter cloacae, 2 Escherichia coli and one Citrobacter freundii). Thirty‐three isolates were ESBL positive and harboured group 1 CTX‐M 1 &bgr;‐lactamases. In addition to the &bgr;‐lactam resistance genes detected by PCR (blaSHV‐1, blaOXA‐48 and blaOXA‐1), WGS of five representative isolates revealed the presence of genes encoding aminoglycoside resistance, aadA2 and aph3‐Ia, fluoroquinolone resistance determinants aac(6)Ib‐c, oqxA and oqxB, the sulfonamide resistance gene sul1, and fosA (fosfomycin resistance). IncL plasmid was found in all isolates. Two K. pneumoniae isolates belonged to ST16, two E. cloacae to ST66 and E. coli to ST354. K. pneumoniae isolates were allocated to five clusters by PFGE which occured in different hospitals, indicating epidemic spread. Conclusions. The OXA‐48‐positive organisms found in this study showed wide variability in antibiotic susceptibility, &bgr;‐lactamase content and PFGE banding patterns. This study revealed a switch from the predominance of VIM‐1 in 2012–2013 to that of OXA‐48 in the 2015 to 2017.

Synthesis, anti-bacterial and anti-protozoal activities of amidinobenzimidazole derivatives and their interactions with DNA and RNA

Abstract Amidinobenzimidazole derivatives connected to 1-aryl-substituted 1,2,3-triazole through phenoxymethylene linkers 7a–7e, 8a–8e, and 9a–9e were designed and synthesised with the aim of evaluating their anti-bacterial and anti-trypanosomal activities and DNA/RNA binding affinity. Results from anti-bacterial evaluations of antibiotic-resistant pathogenic bacteria revealed that both o-chlorophenyl-1,2,3-triazole and N-isopropylamidine moieties in 8c led to strong inhibitory activity against resistant Gram-positive bacteria, particularly the MRSA strain. Furthermore, the non-substituted amidine and phenyl ring in 7a induced a marked anti-bacterial effect, with potency against ESBL-producing Gram-negative E. coli better than those of the antibiotics ceftazidime and ciprofloxacin. UV–Vis and CD spectroscopy, as well as thermal denaturation assays, indicated that compounds 7a and 8c showed also binding affinities towards ctDNA. Anti-trypanosomal evaluations showed that the p-methoxyphenyl-1,2,3-triazole moiety in 7b and 9b enhanced inhibitory activity against T. brucei, with 8b being more potent than nifurtimox, and having minimal toxicity towards mammalian cells. Graphical Abstract

The First Evidence of Epidemic Strain Clostridium Difficile (027/NAP1/BI) in Eastern Croatia

case of the first evidence of epidemic strain Clostridium difficile (027/NAP1 (BI) in a patient in Slavonia region (Eastern Croatia) is presented. Clostridium difficile infection presents the leading cause of the antibiotic-associated nosocomial diarrhea and colitis in the industrialized world. PCR-ribotype 027 is a hypervirulent strain with great epidemic potential and since 2005 spread to European countries. A study published in 2011 years did not prove the presence of ribotype 027 in Croatia.

In vitro effect of subminimal inhibitory concentrations of antibiotics on the biofilm formation ability of Acinetobacter baumannii clinical isolates

The ability of A cinetobacter baumannii strains to form biofilm is one of the most important virulence factor which enables bacterial survival in a harsh environment and decreases antibiotic concentration as well. Subminimal inhibitory concentrations (subMICs) of antibiotics may change bacterial ultrastructure or have an influence on some different molecular mechanisms resulting in morphological or physiological changes in bacteria itself. The aim of this study was to determine effects of 1/2, 1/4, 1/8 and 1/16 minimal inhibitory concentrationsof imipenem, ampicillin-sulbactam, azithromycin, rifampicin and colistin on biofilm formation ability of 22 biofilm non-producing and 46 biofilm producing A. baumannii strains (30 weak producing strains and 16 moderate producing strains). Results of this study indicate that 1/2–1/16 MICs of imipenem, azithromycin, and rifampicin can reduce bacterial biofilm formation ability in moderate producing strains (p < 0.05), whereas 1/16 MIC of imipenem and 1/4–1/8 MICs of rifampicin reduce the biofilm formation in weak producing strains (p < 0.05). Statisticaly significant effect was detected among biofilm non-producing strains after their exposure to 1/16 MIC of azithromycin (p = 0.039). SubMICs of ampicillin-sulbactam and colistin did not have any significant effect on biofilm formation among tested A. baumannii strains.