Role of source control in critically ill candidemic patients: a multicenter retrospective study.

PURPOSE: Candidemia is associated with high mortality especially in critically ill patients. Our aim was to identify predictors of mortality among critically ill patients with candidemia with a focus on early interventions that can improve prognosis. METHODS: Multicenter retrospective study. SETTING: This retrospective study was conducted in Intensive Care Units from three European university hospitals from 2015 to 2021. Adult patients with at least one positive blood culture for Candida spp. were included. Patients who did not require source control were excluded. Primary outcome was 14-day mortality. RESULTS: A total of 409 episodes of candidemia were included. Most candidemias were catheter related (173; 41%), followed by unknown origin (170; 40%). Septic shock developed in 43% episodes. Overall, 14-day mortality rate was 29%. In Cox proportional hazards regression model, septic shock (P 0.001; HR 2.20, CI 1.38-3.50), SOFA score ≥ 10 points (P 0.008; HR 1.83, CI 1.18-2.86), and prior SARS-CoV-2 infection (P 0.003; HR 1.87, CI 1.23-2.85) were associated with 14-day mortality, while combined early appropriate antifungal treatment and source control (P < 0.001; HR 0.15, CI 0.08-0.28), and early source control without appropriate antifungal treatment (P < 0.001; HR 0.23, CI 0.12-0.47) were associated with better survival compared to those without neither early appropriate antifungal treatment nor source control. CONCLUSION: Early source control was associated with better outcome among candidemic critically ill patients.

Infective Endocarditis by Capnocytophaga Species-A Narrative Review.

Bacteria belonging to the genus Capnocytophaga are thin, capnophilic, Gram-negative bacilli with tapered ends that include nine species that are isolated from the mouth of humans and animals and, from a phylogenetical perspective, they belong to the family Flavobacteriaceae. Two more species, namely C. endodontalis and C. stomatis have been recovered from a periapical abscess and human and animal infections, respectively. Capnocytophaga spp. can cause serious and potentially life-threatening infections in humans, such as bacteremia and meningitis, most commonly in the context of penetrating trauma as a result of contact with animals, especially after animal bites. Other invasive diseases such as osteomyelitis, septic arthritis, and infective endocarditis (IE) may also occur more rarely. The aim of this study was to review all previously described cases of IE by Capnocytophaga spp. and provide information about the epidemiology, microbiology, antimicrobial susceptibility, clinical characteristics, treatment, and outcomes of this infection. A narrative review based on a search in PubMed, the Cochrane Library, and Scopus was performed. Studies published until 11 September 2023 providing relevant data for IE caused by Capnocytophaga spp. in humans were included. A total of 31 studies containing data from 31 patients were included. A history of dog bites was present in 10 out of 26 patients (38.5%). A prosthetic valve was present in 3 patients (9.7%). The most commonly infected valve was the aortic valve, followed by the tricuspid valve. Fever, embolic phenomena, paravalvular abscess, and sepsis were the most common clinical presentations. Beta-lactams and aminoglycosides were the antimicrobials most commonly used. Surgery was performed in 20 patients (64.5%). Overall mortality reached 16.1%.

A carbapenem-focused antimicrobial stewardship programme implemented during the COVID-19 pandemic in a setting of high endemicity for multidrug-resistant Gram-negative bacteria.

BACKGROUND: Greece is among the countries characterized by high rates of antimicrobial resistance and high consumption of antibiotics, including carbapenems. OBJECTIVES: To measure the impact of a carbapenem-focused antimicrobial stewardship programme (ASP) on the antibiotic consumption and patient outcomes in a Greek tertiary hospital during the COVID-19 pandemic. METHODS: A quasi-experimental, before-after study, comparing a 12 month pre-intervention period with a 12 month intervention period in which a carbapenem-focused ASP was implemented. RESULTS: A total of 1268 patients were enrolled. The proportion of admitted patients who received carbapenems decreased from 4.1% (842 of 20 629) to 2.3% (426 of 18 245) (-1.8%; P < 0.001). A decrease of -4.9 DDD/100 patient-days (PD) (95% CI -7.3 to -2.6; P = 0.007) in carbapenem use and an increase in the use of piperacillin/tazobactam [+2.1 DDD/100 PD (95% CI 1.0-3.3; P = 0.010)] were observed. Thirty-day mortality following initiation of carbapenem treatment and all-cause in-hospital mortality remained unaltered after ASP implementation. In contrast, length of hospital stay increased (median 17.0 versus 19.0 days; P < 0.001), while the risk of infection-related readmission within 30 days of hospital discharge decreased (24.6% versus 16.8%; P = 0.007). In the post-implementation period, acceptance of the ASP intervention was associated with lower daily hazard of in-hospital death [cause-specific HR (csHR) 0.49; 95% CI 0.30-0.80], lower odds of 30 day mortality (OR 0.36; 95% CI 0.18-0.70) and higher rate of treatment success (csHR 2.45; 95% CI 1.59-3.77). CONCLUSIONS: Implementing and maintaining a carbapenem-focused ASP is feasible, effective and safe in settings with high rates of antimicrobial resistance, even during the COVID-19 pandemic.

In search for a synergistic combination against pandrug-resistant A. baumannii; methodological considerations.

PURPOSE: Pending approval of new antimicrobials, synergistic combinations are the only treatment option against pandrug-resistant A. baumannii (PDRAB). Considering the lack of a standardized methodology, the aim of this manuscript is to systematically review the methodology and discuss unique considerations for assessing antimicrobial combinations against PDRAB. METHODS: Post-hoc analysis of a systematic review (conducted in PubMed and Scopus from inception to April 2021) of studies evaluating antimicrobial combination against A. baumannii, based on antimicrobials that are inactive in vitro alone. RESULTS: Eighty-four publications were reviewed, using a variety of synergy testing methods, including; gradient-based methods (n = 11), disk-based methods (n = 6), agar dilution (n = 2), checkerboard assay (n = 44), time-kill assay (n = 50), dynamic in vitro PK/PD models (n = 6), semi-mechanistic PK/PD models (n = 5), and in vivo animal models (n = 11). Several variations in definitions of synergy and interpretation of each method were observed and are discussed. Challenges related to testing combinations of antimicrobials that are inactive alone (with regards to concentrations at which the combinations are assessed), as well as other considerations (assessment of stasis vs killing, clinical relevance of re-growth in vitro after initial killing, role of in vitro vs in vivo conditions, challenges of clinical testing of antimicrobial combinations against PDRAB infections) are discussed. CONCLUSION: This review demonstrates the need for consensus on a standardized methodology and clinically relevant definitions for synergy. Modifications in the methodology and definitions of synergy as well as a roadmap for further development of antimicrobial combinations against PDRAB are proposed.

Importance of antimicrobial stewardship in solid organ transplant recipients: An ESCMID perspective.

BACKGROUND: In the last decades, solid organ transplantation (SOT) has emerged as an important method in the management of chronic kidney, liver, heart, and lung failure. Antimicrobial use has led to a significant reduction of morbidity and mortality due to infectious complications among patients with SOT; however, it can lead to adverse events and drive the development of antimicrobial resistance; thus, antimicrobial stewardship is of extreme importance. Even though there are ongoing efforts of transplant societies to implement principles of antimicrobial stewardship in everyday practice in SOT, there is still a lack of guidelines in this patient population. AIM: The aim of this study was to review the status of antimicrobial stewardship in patients with SOT, highlight its importance from the perspective of an ongoing vivid dialogue among ESCMID experts in the field of antimicrobial stewardship, and depict opportunities for future study in the field. REVIEW: Antimicrobial stewardship programs are important in order to allow appropriate initiation and termination of antimicrobials in SOT recipients, and also aid in the most appropriate dosing and choosing of the route of administration of antimicrobials. Application of already known antimicrobial stewardship principles and application of currently used biomarkers and newly developed molecular rapid diagnostic testing tools can aid to the rationalization of antimicrobial prescribing and to a more targeted treatment of infections. Finally, physicians caring for SOT recipients should be actively involved in antimicrobial stewardship in order to assure optimization of antimicrobial prescribing and become familiar with the principles of antimicrobial stewardship.

C1q Gene Polymorphism Is Associated with Asymptomatic Bacteriuria in Patients with Type 2 Diabetes Mellitus.

Background and Objectives: Asymptomatic bacteriuria (ASB) appears to have a higher prevalence in diabetics and has been associated with various genetic polymorphisms of the innate immune system. Single nucleotide polymorphisms (SNPs) of the C1q gene that encodes for the trigger molecule of the classical complement pathway increase the risk of bacterial infections as well as other diseases. In the present study, we sought to investigate the association of C1q rs292001 (G > A) SNP with ASB in patients with type 2 diabetes (T2D). Materials and Methods: In this case-control study, performed at the University and the Venizeleion General Hospital of Heraklion, Crete, Greece, 75 adult male and female Cretan patients with T2D and ASB and 75 adult male and female Cretan patients with T2D but without ASB were enrolled and genotyped for rs292001 SNP of C1q gene. Genetic analysis was based on the polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RLFPs) methods. Results: Τhe frequency of homozygotes for the G/G genotype of C1q rs292001 was significantly higher in patients with T2D and ASB than in the control group (p-value = 0.0480, OR = 2.952, 95% CI: 1.052−7.542). Conclusions: Τhe present study provides the first evidence of an association between the C1q rs292001 SNP and an increased susceptibility for ASB in an adult Cretan population with T2D, thus suggesting that this SNP can be encountered as a risk factor for the presence of ASB in patients with T2D.

Treatment pattern, prognostic factors, and outcome in patients with infection due to pan-drug-resistant gram-negative bacteria.

The present study investigated the clinical course, treatment pattern, prognostic factors, and outcome of patients with pun-drug resistant (PDR) infections. This was a retrospective single-center cohort study including consecutive eligible patients with a PDR infection hospitalized at the University Hospital of Heraklion, Crete, Greece, between January 2010 and June 2018. In total, 65 patients with infections due to PDR gram-negative pathogens were identified. The median age was 64 years (interquartile range, IQR: 45.5-74.5) and the median Charlson comorbidity index 3.0 (IQR: 1.0-5.75). Of the 65 PDR isolates, 31 (48%) were Klebsiella pneumoniae, 28 (43%) Acinetobacter baumannii, and 6 (9%) Pseudomonas aeruginosa. The most common empirical therapy was colistin-based combination (n = 32; 49%), followed by non-colistin, non-tigecycline combination (n = 25; 39%), and carbapenemes + tigecycline (n = 8; 12%). The empirical therapy was effective in 50%, 37.5%, and 8% of patients receiving colistin combination, carbapenemes - tigecycline, and non-colistin, non-tigecycline combination, respectively (p value = 0.003). The infection-related in-hospital mortality was 32% (95% confidence interval, CI: 21-45%). Three factors were significantly associated with infection-related in-hospital mortality in multivariate analysis: Charlson comorbidity index (odds ratio, OR: 1.5, 95% CI: 1.0-2.3, p value = 0.030), prior steroid use (OR: 4.1, 95% CI: 1.0-17.0, p value = 0.049), and empirical treatment with non-colistin, non-tigecycline combination (OR: 7.5; 95% CI: 1.7-32.8, p value = 0.008). Infections due to PDR pathogens are associated with considerable mortality. Our results support the use of colistin and/or tigecycline-based combinations as empirical therapy when infection due to PDR pathogens is suspected.

Kodamaea ohmeri infections in humans: A systematic review.

BACKGROUND: Kodamaea ohmeri, previously known as Pichia ohmeri or Yamadazyma ohmeri, belongs to the Saccharomycetaceae family and the Ascomycetae class, is the telomorphic form of C guilliermondii var. membranaefaciens and is frequently mistaken for Candida, as they belong to the same family. It has been isolated from environmental sources, such as sand, pools, seawater and fruits, while the last decades it is recognised as a rare pathogen that causes life-threatening infections in humans. The purpose of this study was to systemically review all published cases of K ohmeri infections in the literature and describe the epidemiology, microbiology, antimicrobial susceptibility, treatment and outcomes of these infections in humans. METHODS: Systematic review of PubMed (through 27th December 2019) for studies providing epidemiological, clinical, microbiological as well as treatment data and outcomes of K ohmeri infections. RESULTS: A total of 35 studies, containing data of 44 patients, were included in the analysis. The most common K ohmeri infections were those of the bloodstream, infective endocarditis and onychomycosis. Previous antibiotic use, presence of a central venous catheter, parenteral nutrition and cancer were very common among patients. Mortality was high in the case of fungemias but low for other types of infections. Amphotericin B and fluconazole are the most common agents used for treatment, even though alarming MICs for fluconazole were noted. CONCLUSIONS: This systematic review thoroughly describes infections by K ohmeri and provides information on their epidemiology, clinical presentation, microbiology, antibiotic resistance patterns, treatment and outcomes.

Fungal endocarditis in transplant recipients: A systematic review.

BACKGROUND: Invasive fungal infections remain a major cause of morbidity and mortality in transplant recipients. Moreover, Fungal Infective Endocarditis (FIE) is a rare infection that carries a higher mortality than bacterial IE in normal host, while in transplant recipients may be even higher. The purpose of this study was to systemically review all published cases of FIE in solid organ and allogeneic bone marrow transplant recipients, describe the epidemiology, microbiology, clinical characteristics, treatment and outcomes of these infections, and to identify risk factors for mortality by FIE. METHODS: A systematic review of PubMed, Scopus and Cochrane Library (through 20 May 2020) for studies providing epidemiological, clinical, microbiological and treatment data and outcomes of FIE in transplant recipients was performed. RESULTS: A total of 60 studies, containing data of 72 patients, were included. The most common transplants were those of the kidney and the liver, while the commonest causative pathogen was Aspergillus. Mitral valve was the commonest infected intracardiac site, followed by mural endocardium. Diagnosis was made with transthoracic echocardiography in 44.3%, while the diagnosis was made at autopsy in 37.3%. Embolic phenomena were the commonest clinical presentation, followed by fever, heart failure and endophthalmitis. Amphotericin B, voriconazole and caspofungin were the commonest antifungals used for treatment of FIE. Clinical cure was noted in 26.9%, while overall mortality was 78.6%. Amphotericin B or caspofungin use was negatively associated with overall mortality. CONCLUSIONS: This systematic review thoroughly describes IE in transplant recipients and provides information on epidemiology, clinical presentation, treatment and outcomes.

Rhodotorula species infections in humans: A systematic review.

BACKGROUND: Fungal infections by Rhodotorula species are increasingly reported in the literature and consist of bloodstream infections, especially in patients with central venous catheters (CVC), as well as central nervous system (CNS), ocular and other less frequent infections. OBJECTIVES: The aim of this systematic review was to record and evaluate all available evidence regarding infections by Rhodotorula species. METHODS: Systematic review of PubMed (through 9 August 2017) for studies providing epidemiological, clinical, microbiological, as well as treatment data and outcomes of Rhodotorula species infections. RESULTS: A total of 111 studies, containing data of 248 patients, were eventually included in the analysis. The most common Rhodotorula infections were those of bloodstream, CNS and ocular infections, as well as peritoneal dialysis-associated peritonitis. Epidemiology of each type of infection was different, with the bloodstream ones being more common in patients with malignancy and CVCs, while those of the CNS were more common in patients with AIDS. Mortality was variable being higher in CNS infections. Amphotericin B remains the most common agent used for treatment, irrespectively of the infection site. CONCLUSIONS: This systematic review thoroughly describes fungal infections by Rhodotorula species and provides information on their epidemiology, clinical picture, microbiology, treatment and outcomes.

Fungal infections in patients with inflammatory bowel disease: A systematic review.

BACKGROUND: Despite reports of fungal infections in patients with inflammatory bowel disease (IBD), their clinical and microbiological characteristics remain unknown. OBJECTIVES: The aim of this systematic review was to examine all available evidence regarding fungal infections in patients with IBD. METHODS: Systematic search of PubMed (through 27 May 2017) for studies providing data on clinical, microbiological, treatment and outcome data of fungal infections in patients with IBD. The primary study outcome was to record the most common fungal species in patients with IBD. Secondary outcomes were classified into 3 categories: (i) characteristics of fungal infections; (ii) data on IBD and (iii) treatment and outcomes of fungal infections in patients with IBD. RESULTS: Fourteen studies with data on 1524 patients were included in final analysis. The most common fungal infections in patients with IBD were caused by Candida species (903 infections); the most commonly reported site of Candida infection was the gastrointestinal tract. Available evidence shows that most fungal infections occur within 12 months of IBD treatment and within 6 months when anti-TNFa agents are used. CONCLUSIONS: This systematic review thoroughly describes fungal infections in patients with IBD and provides important information for the early detection and management of these infections.

Albumin Enhances Caspofungin Activity against Aspergillus Species by Facilitating Drug Delivery to Germinating Hyphae.

The modest in vitro activity of echinocandins against Aspergillus implies that host-related factors augment the action of these antifungal agents in vivo. We found that, in contrast to the other antifungal agents (voriconazole, amphotericin B) tested, caspofungin exhibited a profound increase in activity against various Aspergillus species under conditions of cell culture growth, as evidenced by a ≥4-fold decrease in minimum effective concentrations (MECs) (P = 0. 0005). Importantly, the enhanced activity of caspofungin against Aspergillus spp. under cell culture conditions was strictly dependent on serum albumin and was not observed with the other two echinocandins, micafungin and anidulafungin. Of interest, fluorescently labeled albumin bound preferentially on the surface of germinating Aspergillus hyphae, and this interaction was further enhanced upon treatment with caspofungin. In addition, supplementation of cell culture medium with albumin resulted in a significant, 5-fold increase in association of fluorescently labeled caspofungin with Aspergillus hyphae (P < 0.0001). Collectively, we found a novel synergistic interaction between albumin and caspofungin, with albumin acting as a potential carrier molecule to facilitate antifungal drug delivery to Aspergillus hyphae.

Ewingella americana Infections in Humans-A Narrative Review.

Ewingella americana is a Gram-negative rod that belongs to the order Enterobacterales and the family Yersiniaceae and was first identified in 1983 from 10 clinical strains in the United States of America. The present study aimed to identify all the published cases of E. americana in the literature, describe the epidemiological, clinical, and microbiological characteristics, and provide data regarding its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a PubMed and Scopus databases search. In total, 16 studies provided data on 19 patients with infections by E. americana. The median age of the patients was 55 years, and 47.4% were male. The most common infections were those of the bloodstream, the respiratory tract, and the peritoneal cavity. Antimicrobial resistance to cephalosporins, aminoglycosides, and the combination of trimethoprim with sulfamethoxazole was minimal, and these were the most commonly used antimicrobials for treating these infections. No included study provided information on the genetic or molecular mechanism of this pathogen's antimicrobial resistance. The overall mortality was minimal, with only one patient with bacteremia succumbing to the infection. Further studies are needed to better understand this microorganism, its pathogenic potential in humans, and the genetic and molecular mechanisms underlying its antimicrobial resistance, for which very little evidence exists to date.

Cellulosimicrobium Infections in Humans-A Narrative Review.

Cellulosimicrobium species (formerly known as Oerskovia) are Gram-positive filamentous bacteria in the family Promicromonosporaceae and are more commonly found in sewage and soil. The present study aimed to identify all the published cases of Cellulosimicrobium species infections in the literature, describe the epidemiological, clinical, and microbiological characteristics, and provide data regarding its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a PubMed and Scopus database search. In total, 38 studies provided data on 40 patients with infections by these species. The median age of patients was 52.5 years, and 55% were male. The most common infection types were bacteremia, infective endocarditis (IE), osteoarticular infections, peritoneal dialysis-associated peritonitis, and endophthalmitis. Antimicrobial resistance to vancomycin and the combination of trimethoprim and sulfamethoxazole was minimal, and vancomycin was the most commonly used antimicrobial for treating these infections. Overall mortality was minimal for all infections, except for bacteremia and IE, which carried high mortality rates.

Robinsoniella peoriensis Infections in Humans-A Narrative Review.

Robinsoniella peoriensis is a Gram-positive, strictly anaerobic, spore-forming, rod-shaped bacterium belonging to the phylum Firmicutes and the family Lachnospiraceae. Until now, R. peoriensis is the only species of its genus. It was first isolated in 2003 during a study into the flora of lagoons and manure pits. Given the rarity of this microorganism and the sparse information in the literature about its way of transmission, the way to diagnose its infections and identify it in the microbiology laboratory, and its public health relevance, the present study aimed to identify all the published cases of Robinsoniella, describe the epidemiological, clinical, and microbiological characteristics, and provide information about its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a Pubmed/Medline and Scopus databases search. In total, 14 studies provided data on 17 patients with infections by Robinsoniella. The median age of patients was 63 years and 47% were male. The most common types of infection were bone and joint infections, bacteremia, infective endocarditis, and peritonitis. The only isolated species was R. peoriensis, and antimicrobial resistance to clindamycin was 50%, but was 0% to the combination of piperacillin with tazobactam, aminopenicillin with a beta-lactamase inhibitor, and metronidazole which were the most commonly used antimicrobials for the treatment of these infections. The overall mortality depends on the type of infection and is notable only for bacteremia, while all other infections had an optimal outcome. Future studies should better assess these infections' clinical and epidemiological characteristics and the mechanisms of the antimicrobial resistance of this microorganism from a mechanistic and genetic perspective.

Nanotechnology in the Diagnosis and Treatment of Antibiotic-Resistant Infections.

The development of antimicrobial resistance (AMR), along with the relative reduction in the production of new antimicrobials, significantly limits the therapeutic options in infectious diseases. Thus, novel treatments, especially in the current era, where AMR is increasing, are urgently needed. There are several ongoing studies on non-classical therapies for infectious diseases, such as bacteriophages, antimicrobial peptides, and nanotechnology, among others. Nanomaterials involve materials on the nanoscale that could be used in the diagnosis, treatment, and prevention of infectious diseases. This review provides an overview of the applications of nanotechnology in the diagnosis and treatment of infectious diseases from a clinician's perspective, with a focus on pathogens with AMR. Applications of nanomaterials in diagnosis, by taking advantage of their electrochemical, optic, magnetic, and fluorescent properties, are described. Moreover, the potential of metallic or organic nanoparticles (NPs) in the treatment of infections is also addressed. Finally, the potential use of NPs in the development of safe and efficient vaccines is also reviewed. Further studies are needed to prove the safety and efficacy of NPs that would facilitate their approval by regulatory authorities for clinical use.

Fungemia by Wickerhamomyces anomalus-A Narrative Review.

Wickerhamomyces anomalus has been previously classified as Hansenula anomala, Pichia anomala, and Candida pelliculosa and was recently reclassified in the genus Wickerhamomyces after phylogenetic analysis of its genetic sequence. An increasing number of reports of human infections by W. anomalus have emerged, suggesting that this microorganism is an emerging pathogen. The present review aimed to provide data on the epidemiology, antifungal resistance, clinical characteristics, treatment, and outcomes of fungemia by W. anomalus by extracting all the available information from published original reports in the literature. PubMed/Medline, Cochrane Library, and Scopus databases were searched for eligible articles reporting data on patients with this disease. In total, 36 studies involving 170 patients were included. The age of patients with fungemia by W. anomalus ranged from 0 to 89 years; the mean age was 22.8 years, the median age was 2.2 years, with more than 37 patients being less than one month old, and 54% (88 out of 163 patients) were male. Regarding patients' history, 70.4% had a central venous catheter use (CVC), 28.7% were on total parenteral nutrition (TPN), 97% of neonates were hospitalized in the neonatal ICU (NICU), and 39.4% of the rest of the patients were hospitalized in the intensive care unit (ICU). Previous antimicrobial use was noted in 65.9% of patients. The most common identification method was the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in 34.1%, VITEK and VITEK 2 in 20.6%, and ID32 C in 15.3%. W. anomalus had minimal antifungal resistance to fluconazole, echinocandins, and amphotericin B, the most commonly used antifungals for treatment. Fever and sepsis were the most common clinical presentation noted in 95.8% and 86%, respectively. Overall mortality was 20% and was slightly higher in patients older than one year. Due to the rarity of this disease, future multicenter studies should be performed to adequately characterize patients' characteristics, treatment, and outcomes, which will increase our understanding and allow drawing safer conclusions regarding optimal management.