Denis Swolana

Background: Cardiac implantable electronic device (CIED) infections require transvenous lead extraction, followed by 2–6 weeks of antimicrobial treatment. Case presentation: This series describes CIED infection cases treated with the long-acting lipoglycopeptide antibiotic oritavancin, based on preliminary data from the ORI-4-CIEDi study (ClinicalTrials.gov ID: NCT07013552). Eleven patients (2 women), with a median age of 67.0 years (range 28.0–78.0), received oritavancin administered as a single dose or as multiple doses at 7-day intervals. The etiological factors included: (1) methicillin-sensitive (MS) or methicillin-resistant (MR) coagulase-negative staphylococci (CoNS) in three cases; (2) MS Staphylococcus aureus and MS-CoNS; (3) MR-CoNS and vancomycin-resistant (VRE) Enterococcus faecium; (4) vancomycin-intermediate S. aureus and VRE E. faecium; (5) MR-CoNS, Corynebacterium spp., Peanibacillus humicus, and Acinetobacter baumannii; and (6) Gram-positive rod Bacillus cereus. In two cases, oritavancin therapy was continued empirically. In one case, only Gram-negative bacillus Pseudomonas stutzeri was cultured, leading to discontinuation of oritavancin. Nine participants (81.8%) underwent transvenous lead extraction (TLE), one (9.1%) received pocket debridement and relocation, and one (9.1%) was managed conservatively. Definitive treatment success, defined as a clinical response without recurrence of infection during the 3-month follow-up, was achieved in five participants (62.5%) with infections involving Gram-positive cocci and in two participants (100.0%) with infection of unknown etiology, including one managed conservatively. In two cases infected with Gram-positive cocci, follow-up after TLE was discontinued prematurely due to death from cardiogenic shock, and only complete healing of the surgical wound was observed. In the patient who had undergone non-radical surgery, long-term suppressive therapy against CoNS proved ineffective. Discussion: Weekly administration of long-acting oritavancin in CIED infections with Gram-positive cocci has the potential to enhance patient comfort and support outpatient parenteral antimicrobial therapy. Conclusions: These preliminary findings are encouraging; however, outcomes should be interpreted within the context of the overall treatment strategy, including source-control procedures and combined antimicrobial therapy, rather than attributing results solely to oritavancin.

Introduction: Bacterial multidrug resistance (MDR) drives treatment with expensive, toxic, or pharmacokinetically suboptimal antibiotics. Objectives: To assess the prevalence of MDR Gram-positive cocci among isolates from cardiac implantable electronic device (CIED) infections at a Polish reference center. Methods: Data come from the “EXTRACT” registry (ClinicalTrials.gov ID NCT05775783), which covers 702 transvenous lead extraction procedures. Blood samples and intraoperative swabs were collected from participants with CIED infection. Results: From 209 cases with isolated pocket infection (PI) (107, 51.2%) or systemic infections (102, 48.8%), 263 Gram-positive cocci were cultured. They were: coagulase-negative staphylococci (CoNS) (177, 67.3%), Staphylococcus aureus (62, 23.6%), enterococci (15, 5.7%), streptococci (8, 3.0%), and others (1, 0.4%). The highest MDR rate was among CoNS (46.9%). CoNS exhibited methicillin resistance (MR-CoNS) in 55.9% with co-resistance to macrolides (73.2%), lincosamides (51.0%), fluoroquinolones (56.1%), aminoglycosides (41.4%), tetracyclines (29.6%), and co-trimoxazole (29.3%). Resistance to daptomycin (5.3%) and linezolid (2.0%) in MR-CoNS was rare. The frequency of MDR S. aureus was 8.1%. Methicillin resistance in S. aureus (MRSA, 6.5%) co-occurred with resistance to macrolides/lincosamides and fluoroquinolones (100% for both) or linezolid (25.0%). All MDR staphylococci were vancomycin-susceptible. High-level aminoglycoside resistance (HLAR) in Enterococcus faecalis (53.8%) was accompanied by levofloxacin co-resistance (66.7%). Conversely, E. faecium HLAR (50.0%) strains showed 100.0% β-lactam resistance. Vancomycin-resistant enterococci (VRE) accounted for 6.7%; the VRE E. faecium strain was tigecycline- and linezolid-susceptible. Among viridans group streptococci, β-lactam and lincosamides resistance was common (40.0% for both), with 50.0% of co-resistance. Conclusions: Epidemiological data may improve the effectiveness of empirical antibiotic therapy for CIED-related infections.

Staphylococcus epidermidis (S. epidermidis) poses a significant clinical challenge, particularly in the context of biofilm-associated infections, with increasing antibiotic resistance further complicating infection eradication. In the present study, the effects of cinnamic acid and its derivatives (ferulic acid, p-coumaric acid, and sinapic acid), alone and in combination with the β-lactam antibiotic cloxacillin, on biofilm formation by a single methicillin-resistant S. epidermidis (MRSE) clinical strain were explored. The expression of the biofilm-associated icaADBC operon genes and the icaR repressor gene was assessed using Real-Time PCR as an exploratory analysis under sub-minimal inhibitory concentrations (sub-MICs) of the tested compounds. Furthermore, confocal microscopy was used to qualitatively assess selected structural changes in the biofilm. Their occurrence was demonstrated depending on the fractional inhibitory concentration (FIC) levels used. The results revealed variable and nonlinear patterns of gene expression in response to the tested concentrations. Additionally, compound-dependent differences in anti-biofilm-related responses were observed. Overall, the findings provide insight into the potential influence of cinnamic acid derivatives combined with cloxacillin on biofilm-associated processes in S. epidermidis.

Background: Globalization, increased mobility, changes in dietary habits, and a growing number of immunocompromised patients have heightened exposure to rare or opportunistic pathogens. Here, we present a case of cardiac implantable electronic device-related infective endocarditis (CIED-IE) caused by Bacillus cereus bacteremia originating in the gastrointestinal tract. Case presentation: A 66-year-old female, who had a cardiac resynchronization pacemaker (CRT-P) implanted in 2017 due to second-degree atrioventricular block and left bundle branch block, had undergone device replacement due to battery depletion 4 months earlier and was scheduled for transvenous lead extraction (TLE) due to generator pocket infection. During the TLE procedure, transoesophageal echocardiography revealed vegetations on the leads and in the right atrium. Standard empirical therapy covering methicillin-resistant Staphylococci and Gram-negative bacteria was administered, including oritavancin and gentamicin. Surprisingly, intraoperative samples cultured B. cereus, a Gram-positive, spore-forming rod that usually causes food poisoning through contamination of rice and other starchy foods. B. cereus is generally resistant to β-lactam antibiotics except for carbapenems but is susceptible to glycopeptides. The oritavancin treatment was extended to four fractionated doses (1200, 800, 800, and 800 mg) administered at 7-day intervals. To eradicate bacteria in the gastrointestinal tract, oral vancomycin (125 mg 4 times a day) was added. After 4 weeks of effective antibiotic therapy, a CRT-P with a left bundle branch area pacing lead was reimplanted on the right subclavian area, with no recurrence of infection during the 3-month follow-up. Clinical discussion: In the patient, a diet high in rice and improper storage of rice dishes, together with habitual constipation, were identified as risk factors for the development of invasive Bacillus cereus infection. However, the long half-life lipoglycopeptide antibiotic, oritavancin, administered weekly, proved effective in treating CIED-IE. Conclusions: Infection with rare or opportunistic microorganisms may require extended microbiological diagnostics and non-standard antibiotic therapy; therefore, the medical history should consider risk factors for such infections.

Not available Keywords: drug resistance Gram-positive bacterial infections healthcare associated infections infective endocarditis infectious skin diseases transvenous lead extraction

Staphylococcus epidermidis is a widely prevalent microorganism whose key virulence factors include a high ability to adhere to synthetic surfaces and the capacity to form biofilms. The widespread distribution of multidrug-resistant strains (e.g., MRSE—methycillin-resistant Staphylococcus epidermidis) compels researchers to explore new therapeutic approaches. Cinnamic acid and its derivatives are common plant-derived compounds known for their broad range of biological activities, including antimicrobial properties. The phenotypic assays conducted in this study revealed a strong anti-biofilm activity of the investigated compounds. Confocal laser scanning microscopy allowed for the visualization of structural changes within the biofilm and facilitated the assessment of bacterial cell viability in relation to the concentration of the tested substances.

Pochodne kwasu cynamonowego stanowią szeroką grupę naturalnych związków fenolowych, powszechnie występujących w roślinach oraz obecnych w codziennej diecie człowieka. Do najczęściej analizowanych należą kwas cynamonowy (CA), kwas p-kumarowy (CuA), kwas ferulowy (FA) oraz kwas synapinowy (SA). Związki te powstają w szlaku kwasu szikimowego i odgrywają istotną rolę w metabolizmie wtórnym roślin, uczestnicząc m.in. w biosyntezie flawonoidów, kumaryn, czy ligniny. Ich budowa chemiczna, obejmująca układ sprzężonych wiązań podwójnych oraz obecność grup hydroksylowych i metoksylowych, warunkuje zdolność do oddziaływania z wolnymi rodnikami oraz strukturami biologicznymi komórek. Celem niniejszej pracy była analiza dostępnych danych literaturowych, dotyczących aktywności przeciwdrobnoustrojowej kwasu cynamonowego i jego wybranych pochodnych wobec bakterii z rodzaju Staphylococcus, ze szczególnym uwzględnieniem szczepów opornych na antybiotyki (MRSA, VRSA), a także ocena potencjału tych związków w terapii skojarzonej z klasycznymi chemioterapeutykami. W pracy omówiono zarówno wyniki badań prowadzonych z wykorzystaniem surowych ekstraktów roślinnych, jak i analiz opartych na czystych, wyizolowanych związkach. Dostępne dane wskazują, że omawiane kwasy fenolowe wykazują wielokierunkowe działanie biologiczne, obejmujące właściwości przeciwutleniające, przeciwzapalne, przeciwnowotworowe oraz protekcyjne wobec różnych narządów. Mechanizmy ich aktywności antyoksydacyjnej wiążą się z neutralizacją reaktywnych form tlenu (ROS), chelatowaniem jonów metali przejściowych oraz modulacją szlaków sygnałowych związanych ze stresem oksydacyjnym (m.in. NF-κB, COX-2). W kontekście działania przeciwdrobnoustrojowego opisano kilka potencjalnych mechanizmów, takich jak zaburzenie transportu glukozy do komórki bakteryjnej, hamowanie syntezy ATP, oddziaływanie z enzymami prokariotycznymi oraz destabilizacja błony cytoplazmatycznej prowadząca do utraty integralności komórkowej. Podsumowując, kwas cynamonowy i jego pochodne wykazują potwierdzoną aktywność przeciwdrobnoustrojową wobec bakterii z rodzaju Staphylococcus, jednak jej siła jest niewystarczająca do zastosowania tych związków jako samodzielnych leków przeciwbakteryjnych. Największy potencjał terapeutyczny wydaje się dotyczyć ich roli jako modulatorów aktywności antybiotyków w terapii skojarzonej. Konieczne są dalsze badania oraz analizy in vivo, które pozwolą określić rzeczywiste znaczenie kliniczne tych obserwacji oraz ocenić bezpieczeństwo i skuteczność proponowanych strategii terapeutycznych.

Staphylococcus epidermidis, a component of human microbiota, may also cause life-threatening opportunistic infections. These are becoming increasingly common infections associated with the implantation of various implants. Due to the exhaustion of antibiotic resources, new substances with antimicrobial activity are being sought. The present study examined the antibacterial effect of cinnamic acid and its derivatives and their combinations with β-lactam antibiotics on the growth of Staphylococcus epidermidis strains isolated from vascular infections. The data obtained during the research indicated that cinnamic acid and its derivatives, sinapic acid, ferulic acid, and p-coumaric acid, have weak antibacterial activity (MIC values at the level of 2048 and 4096 mg/L). The combination of cinnamic acid and its derivatives with β-lactam antibiotics increases the effectiveness of their action and may demonstrate various pharmacological effects depending on the established cutoff.

Nowadays, antibiotic resistance is a major public health problem. Among staphylococci, infections caused by Staphylococcus epidermidis (S. epidermidis) are frequent and difficult to eradicate. This is due to its ability to form biofilm. Among the antibiotic substances, nanosilver is of particular interest. Based on this information, we decided to investigate the effect of nanosilver on the viability, biofilm formation and gene expression of the icaADBC operon and the icaR gene for biofilm and non-biofilm S. epidermidis strains. As we observed, the viability of all the tested strains decreased with the use of nanosilver at a concentration of 5 µg/mL. The ability to form biofilm also decreased with the use of nanosilver at a concentration of 3 µg/mL. Genetic expression of the icaADBC operon and the icaR gene varied depending on the ability of the strain to form biofilm. Low concentrations of nanosilver may cause increased biofilm production, however no such effect was observed with high concentrations. This confirms that the use of nanoparticles at an appropriately high dose in any future therapy is of utmost importance. Data from our publication confirm the antibacterial and antibiotic properties of nanosilver. This effect was observed phenotypically and also by levels of gene expression.

In Poland, the first case of SARS-CoV-2 infection was confirmed in March 2020. Since then, many circulating virus lineages fueled rapid pandemic waves which inflicted a severe burden on the Polish healthcare system. Some of these lineages were associated with increased transmissibility and immune escape. Mutations in the viral spike protein, which is responsible for host cell recognition and serves as the primary target for neutralizing antibodies, are of particular importance. We investigated the molecular epidemiology of the SARS-CoV-2 clades circulating in Southern Poland from February 2021 to August 2021. The 921 whole-genome sequences were used for variant identification, spike mutation, and phylogenetic analyses. The Pango B.1.1.7 was the dominant variant (n = 730, 89.68%) from March 2021 to July 2021. In July 2021, the B.1.1.7 was displaced by the B.1.617.2 lineage with 66.66% in July 2021 and 92.3% in August 2021 frequencies, respectively. Moreover, our results were compared with the sequencing available on the GISAID platform for other regions of Poland, the Czech Republic, and Slovakia. The analysis showed that the dominant variant in the analyzed period was B.1.1.7 in all countries and Southern Poland (Silesia). Interestingly, B.1.1.7 was replaced by B.1.617.2 earlier in Southern Poland than in the rest of the country. Moreover, in the Czech Republic and Slovakia, AY lineages were predominant at that time, contrary to the Silesia region.