Nosocomial Setting Research Articles

Replacement of KPC-producing pandemic lineages and dissemination of plasmids associated with antimicrobial resistance determinants during inpatient’s hospitalization

The emergence of blaKPC-2 within nosocomial settings has become a major public health crisis worldwide. Our aim was to perform whole-genome sequencing (WGS) of three KPC-producing Gram-negative bacilli (KPC-GNB) strains isolated from a hospitalized patient to identify acquired antimicrobial resistance genes (ARGs). WGS was performed using Illumina MiSeq-I, and de novo assembly was achieved using SPAdes. Bioinformatics analysis was done using Resfinder, AMRFinder, ISFinder, plasmidSPAdes, PlasmidFinder, MOB-suite, PLSDB database, and IntegronFinder. Conjugation assays were performed to assess the ability of blaKPC-2 to transfer via a plasmid-related mobilization mechanism. High-risk clone KPC-producing Klebsiella pneumoniae sequence type (ST) 258 (HA3) was colonizing an inpatient who later was infected by KPC-producing Escherichia coli ST730 (HA4) and subsequently by KPC-producing K. pneumoniae ST11 (HA15) during hospitalization. Although belonging to different species, both strains causing infections harbored the same gene configuration for dissemination of blaKPC-2 in related IncM1 plasmids recently found in other KPC-GNB isolated from Hospital Alemán at Ciudad Autónoma de Buenos Aires. Conjugation assays revealed that only pDCVEA4-KPC from E. coli HA4 was successfully transferred with a conjugation frequency of 3.66×101. Interchange of multidrug-resistant K. pneumoniae lineages ST258 replaced by ST11 in the framework of colonization and infection by KPC-GNB of an inpatient from our institution was found. In addition, the transfer of the gene configuration of blaKPC-2 between infecting strains may have occurred in the nosocomial environment, but we cannot rule out that the event took place in vivo, within the patient, during hospitalization.

Update on the Pathogenesis, Virulence, and Treatment of Candida auris.

Candida auris is an emerging, multidrug resistant fungal pathogen that causes considerable morbidity and mortality. First identified in Japan in 2009, it has since been reported in more than 40 countries. C. auris can persist for long periods on different environmental surfaces as well as the skin. Clinical isolates are typically resistant to commonly prescribed antifungal drugs. Increasingly recognized as a cause of infections and outbreaks in nosocomial settings, C. auris is difficult to identify using traditional microbiological methods. One of the main reasons for the ongoing spread of C. auris is the multitude of virulence factors it possesses and uses against its human host that enables fungal persistence on the skin surface. Yet, many of the virulence mechanismsare unknown or remain incompletely understood. In this review, we summarize the evolution of virulence of C. auris, offer recommendations for combating this important human pathogen, and suggest directions for further research.

An Original and Efficient Antibiotic Adjuvant Strategy to Enhance the Activity of Macrolide Antibiotics against Gram-Negative Resistant Strains.

Gram-negative bacteria were reported as a significant cause of infections in both community and nosocomial settings. Considered as one of the greatest threats to public health, the spread of bacteria drug resistance and the lack of effective alternative treatment options remains problematic. Herein, we report a promising strategy to combat Gram-negative resistant strains consisting of the combination of a macrolide antibiotic with a polyaminoisoprenyl adjuvant derivative leading to a significant decrease of antibiotic resistance.

It's Bordetella, It's Alcaligenes… No, It's Achromobacter! Identification, Antimicrobial Resistance, and Clinical Significance of an Understudied Gram-Negative Rod

Gram-negative non-fermentative bacilli, such as Achromobacter spp., can be opportunistic pathogens in nosocomial settings. Widely found in nature, Achromobacter spp. cause a broad spectrum of diseases and are best known as emerging opportunistic pathogens in the lungs of cystic fibrosis patients. Importantly, Achromobacter infections represent a diagnostic and clinical challenge. First, clinical laboratories cannot routinely identify Achromobacter isolates reliably to the species level outside of creating and curating a custom mass spectrometry database or using Achromobacter-specific genotypic molecular methods. Additionally, Achromobacter spp. infections are often difficult to treat owing to numerous intrinsic, and to a lesser extent acquired, antimicrobial resistance mechanisms. Treatment decisions are further complicated by discordance between CLSI and EUCAST breakpoints for antimicrobial susceptibility testing of Achromobacter isolates, and collaboration to harmonize these is necessary. Further studies are also needed to define the clinical spectrum of disease and pathogenic potential of many Achromobacter species.

Prevalence of multidrug resistant non-fermenters in a tertiary care centre

Background: Infections due to multidrug resistant organisms especially Gram-negative non-fermenting bacteria such as Acinetobacter baumannii and Pseudomonas aeruginosa are increasing, ultimately leading to shortage of clinically effective antibiotics. Indiscriminate use of antibiotics is the key factor influencing the prevalence and distribution of drug resistance in any community or nosocomial setting. Aims and Objectives: The objectives of the study are as follows: (1) To know the antibiotic susceptibility pattern of commonly isolated non-lactose fermenters. (2) To know the prevalence of multidrug resistant P. aeruginosa and A. baumannii. Materials and Methods: Clinical samples from various departments were processed using standard isolation and identification procedures. Only non-lactose fermenting colonies were processed further and only those isolates that were identified as P. aeruginosa and A. baumannii. were considered and their antibiotic susceptibility testing by disk diffusion method was carried out. Results were tabulated and analyzed. Results: Among 558 non-lactose fermenting Gram-negative bacilli isolates, P. aeruginosa (355) and A. baumannii. (203) were the most common isolates. Resistance to commonly used drugs such as aminoglycosides, cephalosporins and inhibitor combinations, and fluoroquinolones ranged from 40% to 65%. Carbapenem resistant isolates were around 24–25%. Multidrug resistant isolates and extensively drug resistant accounted for 17.4% and 9.1%, respectively. Conclusion: Increasing multidrug resistance and extensive drug resistance resistance among non-fermenters are on the rise leaving a very small window of treatment options. This is an alarming situation that needs strict antibiotic policy and a robust antimicrobial resistance management plan.

Whole-cell vaccine candidates induce a protective response against virulent Acinetobacter baumannii.

Acinetobacter baumannii causes multi-system diseases in both nosocomial settings and a pre-disposed general population. The bacterium is not only desiccation-resistant but also notoriously resistant to multiple antibiotics and drugs of last resort including carbapenem, colistin, and sulbactam. The World Health Organization has categorized carbapenem-resistant A. baumannii at the top of its critical pathogen list in a bid to direct urgent countermeasure development. Several early-stage vaccines have shown a range of efficacies in healthy mice, but no vaccine candidates have advanced into clinical trials. Herein, we report our findings that both an ionizing γ-radiation-inactivated and a non-ionizing ultraviolet C-inactivated whole-cell vaccine candidate protects neutropenic mice from pulmonary challenge with virulent AB5075, a particularly pathogenic isolate. In addition, we demonstrate that a humoral response is sufficient for this protection via the passive immunization of neutropenic mice.

Molecular study of quorum sensing and biofilm formation genes in Pseudomonas aeruginosa isolated from UTIs patients

Background: Urinary tract infection (UTI) is a common health problem in both community and nosocomial settings, affecting both men and women equally. Pseudomonas aeruginosa is an opportunistic human pathogen causing devastating acute and chronic infections in individuals with compromised immune systems. Biofilm is an architecture built mostly by autogenic extracellular polymeric substances which function as a scaffold to encase the bacteria together on surfaces, and to protect them from environmental stresses, impedes phagocytosis and thereby conferring the capacity for colonization and long-term persistence. So, the aim of this study to screen of some important quorum sensing and biofilm genes among pseudomonas aeruginosa isolated from UTIs patients. Methods: These study was conducted in Al-Qadisiyah province, Iraq at five major hospitals (AL-Diwanyia Teaching Hospital, Feminine and children teaching hospital, Afak General Hospital, AL-Hamzah General Hospital and AL-Shamiya General Hospital) during the period from (November, 2020 to June, 2021). A total of 800 urine samples were collected from male and females referring to five major hospitals. The age of the patients ranged from (1 to 80) years-old. Results: Sixty isolates were showed positive and identified as P. aeruginosa by using selective media, biochemical test system and VITEK-2 compact system.

Replacement of the Dominant ST191 Clone by ST369 Among Carbapenem-Resistant Acinetobacter baumannii Bloodstream Isolates at a Tertiary Care Hospital in South Korea.

The clonal dissemination of carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia is a serious clinical problem worldwide. However, the factors related to the emergence and replacement of predominant CRAB clones in nosocomial settings are unclear. By multilocus sequence typing (MLST), we evaluated the genetic relatedness of CRAB bloodstream isolates at a tertiary care hospital over a 3.5-year period and investigated the clinical and microbiologic characteristics of the predominant sequence types (STs). One hundred and seventy-nine CRAB bloodstream isolates were collected from June 2016 to December 2019, and their MLSTs according to Oxford scheme and clinical data were obtained. The predominant STs were assessed for in vitro growth, competitive growth, and virulence in a mouse model of intraperitoneal infection. Two dominant clones—ST369 (n = 98) and ST191 (n = 48)—belonging to international clone 2 (IC2) were recovered from patients admitted to intensive care units (ICUs) or wards. ST191 predominated (61%, 27/43) from June 2016 to July 2017, whereas ST369 (72%, 98/136), which was first isolated from a patient admitted to the emergency room, replaced ST191 (15%, 21/136) after August 2017. In a multivariate analysis, leukopenia (OR = 3.62, 95% CI 1.04–12.6, p = 0.04) and ST191 or 369 (OR = 5.32, 95% CI 1.25–22.65, p = 0.02) were independent risk factors for 7-day mortality. Compared with non-ST369, ST369 was associated with a shorter time to bacteremia from ICU admission (7 vs. 11 days, p = 0.01), pneumonia as an origin of bacteremia (67 vs. 52%, p = 0.04), leukopenia (28 vs. 11%, p < 0.01), and a lower 7-day survival rate (41 vs. 70%, p < 0.01). In vitro, ST 369 isolates had significantly higher growth rates and enhanced competitive growth compared to ST191. Finally, ST369 had greater virulence and a higher mortality rate than other STs in a mouse infection model. We report almost-complete replacement of the predominant ST191 clone by ST369 within an 8-month period at our hospital. ST369 had a high incidence density rate of CRAB bacteremia, a short time to bacteremia after ICU admission, and a high early mortality rate, which may be in part explained by its faster competitive growth rate and higher virulence than ST191.

Performance Evaluation of the IR Biotyper® System for Clinical Microbiology: Application for Detection of Staphylococcus aureus Sequence Type 8 Strains.

Background: Methicillin-resistant S. aureus (MRSA) clonal lineages have been classified based on sequence type (ST) and pulsotype associated with human infection. Providing rapid and accurate epidemiological insight is important to address proper infection control in both community-acquired and nosocomial hospital settings. In this regard, this study was performed to evaluate the IR Biotyper® (IRBT®) for strain typing of S. aureus clinical isolates on three media. Methods: A total of 24 S. aureus clinical isolates comprising 15 MRSA isolates (six ST5, three ST72, three ST8, and three ST188 isolates) and nine methicillin-susceptible S. aureus (MSSA) isolates (three ST5, three ST72, and three ST8 isolates) were included for evaluating the IRBT®. Molecular characterization of all S. aureus isolates was performed by conventional PCR and sequencing methods. The IRBT® was evaluated according to manufacturer instructions and a modified sample procedure on commonly used BAP, MHA, and TSA media. Subsequently, the spectra obtained by IRBT® software were compared with dendrograms of PFGE analysis. Results: In this study, the modified sample procedure for reducing the amount of bacteria and bacterial concentration improved the acquisition quality pass rate of the IRBT®. Each spectrum of S. aureus ST5, ST72, and ST188 isolates on all three media could not be clustered by IRBT®. However, the dendrogram obtained from the spectra of S. aureus ST8 isolates on TSA medium were in concordance with that obtained by PFGE analysis. In addition, the visual distribution of S. aureus ST8 isolates on TSA medium in a 2D scatter plot appeared as separated point set from those of S. aureus ST5, ST72, and ST188 isolates. Conclusions: The IRBT® system is a rapid strain typing tool using the FTIR spectroscopic method. This system demonstrated the possibility of discriminating the strain types of S. aureus clinical isolates. Indeed, S. aureus ST8 isolates on TSA medium were successfully differentiated from other strain type isolates.

Emerging strategies for environmental decontamination of the nosocomial fungal pathogen Candida auris.

Candida auris is a recently emerged multidrug-resistant fungal pathogen that causes life-threatening infections to the human population worldwide. Recent rampant outbreaks of C. auris in coronavirus disease 2019 (COVID-19) patients, together with outbreaks in over 45 countries, highlight its threat to patients and healthcare economies. Unlike other pathogenic Candida species, C. auris is capable of surviving in abiotic surfaces of healthcare facilities for prolonged periods, leading to increased risk of transmission within nosocomial settings. C. auris is resistant to multiple classes of antifungal agents, forms dry biofilms and transmits independently to regional epicentres, making its eradication from nosocomial environment arduous. The lack of strategies for environmental decontamination of C. auris from nosocomial settings is evident from the generic guidance and recommendations provided by leading global healthcare bodies. Therefore, this minireview discusses the current guidelines for environmental decontamination of C. auris and compounds and strategies currently under investigation for potential future use. While established guidelines recommend the use of products mainly consisting of sodium hypochlorite and hydrogen peroxide, initial works have been reported on the promising anti-C. auris properties of various other compounds and some biocompatible alternatives. Further validation of these approaches, coupled up with environmentally friendly decontamination protocols, are warranted to achieve superior elimination of C. auris from healthcare settings.

Effect and characterizations of silver nanoparticles on biofilm formation in Pseudomonas aeruginosa isolated from UTIs patients

Background: Urinary tract infection (UTI) is a common health problem in both community and nosocomial settings, affecting both men and women equally.Pseudomonas aeruginosa is an opportunistic human pathogen causing devastating acuteand chronic infections in individuals with compromised immune systems. Biofilmis an architecture built mostly by autogenic extracellular polymeric substances which function asa scaffold to encase the bacteria together on surfaces, and to protect them from environmentalstresses, impedes phagocytosis and thereby conferring the capacity for colonization and long-termpersistence.The present study aim to evaluate the antibacterial activity of chemo-synthesized AgNPs onbiofilm-forming XDR Pseudomonas aeruginosaisolated from UTIs patients. Methods: These study was conducted in Al-Qadisiyah province, Iraq at five major hospitals (AL-Diwanyia Teaching Hospital,Feminine and children teaching hospital, Afak General Hospital, AL-Hamzah General Hospital and AL-Shamiya General Hospital) during the period from (November, 2020 to June, 2021). A total of 800 urine samples were collected from male and females referring to five major hospitals. The age of the patients ranged from (1 to 80) years-old. Results:Sixty isolates were showed positive and identified as P. aeruginosa by using selective media, biochemical test system and VITEK-2 compact system. Genetically, in the present study, a total DNA was extracted from all clinical P.aeruginosa isolates.

Molecular study of quorum sensing and biofilm formation genes in pseudomonas aeruginosa isolated from UTIs patients

Background: Urinary tract infection (UTI) is a common health problem in both community and nosocomial settings, affecting both men and women equally. Pseudomonas aeruginosa is an opportunistic human pathogen causing devastating acute and chronic infections in individuals with compromised immune systems. Biofilm is an architecture built mostly by autogenic extracellular polymeric substances which function as a scaffold to encase the bacteria together on surfaces, and to protect them from environmental stresses, impedes phagocytosis and thereby conferring the capacity for colonization and long-term persistence. So, the aim of this study to screen of some important quorum sensing and biofilm genes among pseudomonas aeruginosa isolated from UTIs patients. Methods: These study was conducted in Al-Qadisiyah province, Iraq at five major hospitals (AL-Diwanyia Teaching Hospital, Feminine and children teaching hospital, Afak General Hospital, AL-Hamzah General Hospital and AL-Shamiya General Hospital) during the period from (November, 2020 to June, 2021). A total of 800 urine samples were collected from male and females referring to five major hospitals. The age of the patients ranged from (1 to 80) years-old.

Promising Acinetobacter baumannii Vaccine Candidates and Drug Targets in Recent Years.

In parallel to the uncontrolled use of antibiotics, the emergence of multidrug-resistant bacteria, like Acinetobacter baumannii, has posed a severe threat. A. baumannii predominates in the nosocomial setting due to its ability to persist in hospitals and survive antibiotic treatment, thereby eventually leading to an increasing prevalence and mortality due to its infection. With the increasing spectra of drug resistance and the incessant collapse of newly discovered antibiotics, new therapeutic countermeasures have been in high demand. Hence, recent research has shown favouritism towards the long-term solution of designing vaccines. Therefore, being a realistic alternative strategy to combat this pathogen, anti-A. Baumannii vaccines research has continued unearthing various antigens with variable results over the last decade. Again, other approaches, including pan-genomics, subtractive proteomics, and reverse vaccination strategies, have shown promise for identifying promiscuous core vaccine candidates that resulted in chimeric vaccine constructs. In addition, the integration of basic knowledge of the pathobiology of this drug-resistant bacteria has also facilitated the development of effective multiantigen vaccines. As opposed to the conventional trial-and-error approach, incorporating the in silico methods in recent studies, particularly network analysis, has manifested a great promise in unearthing novel vaccine candidates from the A. baumannii proteome. Some studies have used multiple A. baumannii data sources to build the co-functional networks and analyze them by k-shell decomposition. Additionally, Whole Genomic Protein Interactome (GPIN) analysis has utilized a rational approach for identifying essential proteins and presenting them as vaccines effective enough to combat the deadly pathogenic threats posed by A. baumannii. Others have identified multiple immune nodes using network-based centrality measurements for synergistic antigen combinations for different vaccination strategies. Protein-protein interactions have also been inferenced utilizing structural approaches, such as molecular docking and molecular dynamics simulation. Similar workflows and technologies were employed to unveil novel A. baumannii drug targets, with a similar trend in the increasing influx of in silico techniques. This review integrates the latest knowledge on the development of A. baumannii vaccines while highlighting the in silico methods as the future of such exploratory research. In parallel, we also briefly summarize recent advancements in A. baumannii drug target research.

Bacteriophage-Mediated Control of Biofilm: A Promising New Dawn for the Future.

Biofilms are complex microbial microcolonies consisting of planktonic and dormant bacteria bound to a surface. The bacterial cells within the biofilm are embedded within the extracellular polymeric substance (EPS) consisting mainly of exopolysaccharides, secreted proteins, lipids, and extracellular DNA. This structural matrix poses a major challenge against common treatment options due to its extensive antibiotic-resistant properties. Because biofilms are so recalcitrant to antibiotics, they pose a unique challenge to patients in a nosocomial setting, mainly linked to lower respiratory, urinary tract, and surgical wound infections as well as the medical devices used during treatment. Another unique property of biofilm is its ability to adhere to both biological and man-made surfaces, allowing growth on human tissues and organs, hospital tools, and medical devices, etc. Based on prior understanding of bacteriophage structure, mechanisms, and its effects on bacteria eradication, leading research has been conducted on the effects of phages and its individual proteins on biofilm and its role in overall biofilm removal while also revealing the obstacles this form of treatment currently have. The expansion in the phage host-species range is one that urges for improvement and is the focus for future studies. This review aims to demonstrate the advantages and challenges of bacteriophage and its components on biofilm removal, as well as potential usage of phage cocktail, combination therapy, and genetically modified phages in a clinical setting.

Optimal control analysis for a Candida auris nosocomial infection model with environmental transmission

In this paper, we propose a mathematical model to investigate the role of environmental reservoirs in the transmission dynamics of the rising Candida auris infections in nosocomial settings. The ability of the pathogen to resist commonly used hospital disinfectants ensures its persistent contamination of hospital surfaces and medical equipment readily leading to patient colonization. Colonized patients shed the pathogen into their surroundings thereby increasing the fungal concentration in the hospital environment. We analyze the model for its basic mathematical properties, perform sensitivity analysis, and formulate an optimal problem to determine the efficiency of control interventions, namely, standard transmission precautions, proper laboratory identification, and isolation of patients identified with colonization in reducing the contamination and transmission of C. auris infections. We characterize the optimal controls using Pontryagin's Minimum Principle and further prove the uniqueness of the optimality system. Numerical simulations are performed to substantiate the theoretical analysis, and the results are illustrated graphically.

Outbreak of Ralstonia mannitolilytica Infection in Hemato-Oncology Unit: Case Series and Review of Literature

AbstractRalstonia mannitolilytica is a Gram-negative, nonfermentative, soil bacterium that is reported to cause opportunistic infections in immunocompromised patients in nosocomial settings. After extensive review of literature, it was found that this is second outbreak reported from India. This study is a retrospective analysis of the clinical features, outcome, and source identification of R. mannitolilytica infection outbreak in a hemato-oncology unit of a tertiary care center of North India between February 2020 and March 2020. We report an outbreak of R. mannitolilytica bacteremia (with or without septic shock) in five patients admitted in hemato-oncology unit at a tertiary care institute in North India for 1 month period. Four patients were cured after administration of appropriate antibiotics as per sensitivity reports, while one patient died of septicemia due to delayed diagnosis. Environmental cultures revealed multidose saline bottles used for administration of drugs as the source of outbreak. Following implementation of use of single dose diluents and flushing solutions in patients with central venous catheter, no new case was reported. Clinicians and microbiologists should keep high index of suspicion to identify these organisms as timely diagnosis is the only key to improve outcomes.

Emergence of Hypervirulent ST11-K64 Klebsiella pneumoniae Poses a Serious Clinical Threat in Older Patients.

The carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses a severe therapeutic challenge to global public health, and research on CR-hvKP in older patients remain limited. In this study, we aimed to investigate the clinical and molecular characteristics and risk factors of CR-hvKP infections in older patients. We retrospectively investigated older patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in the intensive care unit (ICU) between January 2020 and December 2020. The clinical data, and microbiological data including antimicrobial susceptibility testing, phenotype experiment and detection of carbapenemases, string test, virulence genes, capsular serotype-specific (cps) genes, and multilocus sequence typing, of the CR-hvKP group defined by the presence of any one of the virulence genes, including rmpA, rmpA2, iucA, iroN, and peg-344 were compared with those of CR-non-hvKP strains. Of the 80 CRKP strains, 51 (63.8%) met the definition of CR-hvKP. The main mechanism of resistance to carbapenems was the presence of the blaKPC−2 gene. Sequence type (ST)11 (81.3%, 65/80) and ST15 (16.3%, 13/80) were the most common STs in CRKP strains. The minimum inhibitory concentration (MIC)50 values of the CR-hvKP group against the six tested antibiotics (ceftazidime, ceftazidime-avibactam, imipenem-avibactam, tigecycline, levofloxacin, and Cefoperazone-Sulbactam) exhibited elevated levels than the CR-non-hvKP group. Ceftazidime and imipenem by combining avibactam (4 μg/mL) significantly decreased the MIC90 values more than 16-fold than ceftazidime and imipenem alone against Klebsiella pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae. Cardiovascular disease [odds ratio (OR) = 11.956] and ST11-K64 (OR = 8.385) appeared to be independent variables associated with CR-hvKP infection by multivariate analysis. In conclusion, higher MICs of the last line antibiotic agents (ceftazidime-avibactam, tigecycline) might be a critical consideration in the clinical management of older patients where the concentration of these toxic antibiotics matters because of underlying comorbidities. Caution regarding KPC-2-producing ST11-K64 CR-hvKP as being new significant “superbugs” is required as they are widespread, and infection control measures should be strengthened to curb further dissemination in nosocomial settings in China.

Infecciones por bacilos gramnegativos productores de carbapenemasas

Carbapenemase-producing enterobacteriaceae (CPE) are the Gram-negative bacilli that this type of carbapenemic hydrolysis enzymes most often carry. In particular, Klebsiella pneumoniae is the most common. The carbapenemases KPC, VIM, NDM, IMP, and OXA-48 are the most common. They are usually acquired in a nosocomial setting and are associated with healthcare (time of hospitalization; ICU stay; prior antibiotic therapy; comorbidity; use of vascular catheters, bladder catheters, mechanical ventilation, etc.). They produce symptoms similar those caused by enterobacteriaceae, with urinary tract infections (UTIs) those that have the best prognosis and bacteremias and pneumonias those with greater associated mortality. Antibiotic treatments available include colistin, aminoglycosides, fosfomycin, aztreonam, and tigecycline. Carbapenems can also be used so long as the minimum inhibitory concentration (MIC) allows for them; their combined use is preferred. New available drugs include ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, and eravacycline.

From environmental adaptation to host survival: Attributes that mediate pathogenicity of Candida auris

ABSTRACT Candida species are a major cause of invasive fungal infections. While Candida albicans, C. glabrata, C. parapsilosis, and C. tropicalis are the most dominant species causing life-threatening candidiasis, C. auris recently emerged as a new species causing invasive infections with high rates of clinical treatment failures. To mimic initial phases of systemic Candida infections with dissemination via the bloodstream and to elucidate the pathogenic potential of C. auris, we used an ex vivo whole blood infection model. Similar to other clinically relevant Candida spp., C. auris is efficiently killed in human blood, but showed characteristic patterns of immune cell association, survival rates, and cytokine induction. Dual-species transcriptional profiling of C. auris-infected blood revealed a unique C. auris gene expression program during infection, while the host response proofed similar and conserved compared to other Candida species. C. auris-specific responses included adaptation and survival strategies, such as counteracting oxidative burst of immune cells, but also expression of potential virulence factors, (drug) transporters, and cell surface-associated genes. Despite comparable pathogenicity to other Candida species in our model, C. auris-specific transcriptional adaptations as well as its increased stress resistance and long-term environmental survival, likely contribute to the high risk of contamination and distribution in a nosocomial setting. Moreover, infections of neutrophils with pre-starved C. auris cells suggest that environmental preconditioning can have modulatory effects on the early host interaction. In summary, we present novel insights into C. auris pathogenicity, revealing adaptations to human blood and environmental niches distinctive from other Candida species.

Infections Due to Acinetobacter baumannii-calcoaceticus Complex: Escalation of Antimicrobial Resistance and Evolving Treatment Options.

Bacteria within the genus Acinetobacter (principally A. baumannii-calcoaceticus complex [ABC]) are gram-negative coccobacilli that most often cause infections in nosocomial settings. Community-acquired infections are rare, but may occur in patients with comorbidities, advanced age, diabetes mellitus, chronic lung or renal disease, malignancy, or impaired immunity. Most common sites of infections include blood stream, skin/soft-tissue/surgical wounds, ventilator-associated pneumonia, orthopaedic or neurosurgical procedures, and urinary tract. Acinetobacter species are intrinsically resistant to multiple antimicrobials, and have a remarkable ability to acquire new resistance determinants via plasmids, transposons, integrons, and resistance islands. Since the 1990s, antimicrobial resistance (AMR) has escalated dramatically among ABC. Global spread of multidrug-resistant (MDR)-ABC strains reflects dissemination of a few clones between hospitals, geographic regions, and continents; excessive antibiotic use amplifies this spread. Many isolates are resistant to all antimicrobials except colistimethate sodium and tetracyclines (minocycline or tigecycline); some infections are untreatable with existing antimicrobial agents. AMR poses a serious threat to effectively treat or prevent ABC infections. Strategies to curtail environmental colonization with MDR-ABC require aggressive infection-control efforts and cohorting of infected patients. Thoughtful antibiotic strategies are essential to limit the spread of MDR-ABC. Optimal therapy will likely require combination antimicrobial therapy with existing antibiotics as well as development of novel antibiotic classes.