Life-threatening Bloodstream Infections Research Articles

Occurrence of Cardiotoxicity and the Impact on Outcomes Among Children Treated on the AAML0531 Clinical Trial: A Report from the Children's Oncology Group

Background: Much of the literature on anthracycline-associated cardiotoxicity has focused on late effects of exposure among childhood cancer survivors. Given the high anthracycline exposure in front-line therapy for pediatric acute myeloid leukemia (AML), it is crucial to gain a better understanding of the risk factors for early cardiotoxicity and its impact on subsequent treatment outcomes.Methods: Between August 2006 and June 2010, Children's Oncology Group trial AAML0531 enrolled patients less than 30 years of age for frontline treatment of de novo AML. These analyses excluded Down syndrome patients. Cardiac events over the course of treatment and off-protocol follow-up were ascertained through a combination of passive (traditional adverse event (AE) case report forms) and active (targeted requests for echocardiograms for patients with an AE report for a cardiac event or life-threatening bloodstream infection) adverse event monitoring. The primary outcome of cardiotoxicity was defined as grade 2 or higher left ventricular systolic dysfunction (LVSD) based on Common Terminology Criteria for AE Version 3 definitions (i.e., ejection fraction <50% or fractional shortening <24%). We evaluated risk factors for incident LVSD using multivariable Cox regression analyses. Cox regression models were then used to compare event-free survival (EFS) and overall survival (OS) in patients with documented LVSD, classified as infection-associated and not infection-associated, relative to patients with no documented LVSD. The occurrence of LVSD was considered as a time-varying exposure to avoid immortal and immune person-time bias. Adjusted hazard ratios and corresponding 95% confidence intervals were reported. Cox model predicted survival probabilities were used to plot the OS and EFS curves.Results: These analyses included 1022 AML patients enrolled AAML0531. Compliance with echocardiographic evaluations was higher but more variable during the on-protocol (median: 61.2%, range: 41.1%-85.0%) compared with the off-protocol reporting periods (median: 53.8%, range: 39.1%-56.1%). Compliance did not differ significantly by age, gender, race, ethnicity, BMI, insurance status, AML risk classification, initial white blood cell count, or randomized treatment arm.Approximately 12% of patients had documented grade 2 or higher LVSD over the course of follow-up; 25% of incident events were classified as infection-associated. The cumulative incidence increased approximately linearly during on-protocol therapy from 1% to 8% from Induction I through Intensification III, but plateaued early during off-protocol follow-up (i.e.18 months). The overall incidence increased with age at enrollment (p-value for trend: <0.002), was higher among black compared to white patients (HR=1.73, 95% CI: 1.00, 2.99), among obese compared to normal weight patients (HR=1.64, 95% CI: 1.01, 2.65), and in the setting of a bloodstream infection (HR=1.86, 95% CI: 1.12, 10.9). These overall trends, with the exception of obesity, were driven by on-protocol toxicities.Five-year EFS and OS were significantly lower in patients who experienced on-protocol cardiotoxicity (Table 1, Figure 1). The impact on EFS was similar whether the incident event was determined to be in the presence or absence of infection (absolute differences of 17.5% and 16.1%, respectively), whereas the impact on OS was more pronounced for cardiac toxicity in the absence of infection than cardiac toxicity in the presence of infection (absolute differences of 16.8% and 7.7%, respectively).Conclusions: Our findings demonstrate that early treatment-related cardiotoxicity is associated with decreased EFS and OS possibly through associated reductions in anthracycline exposure. The suggested heterogeneity in the effect on OS by infection status implies that patients who experience LVSD in the context of infection may be more salvageable upon relapse than patients experiencing non-infection related cardiotoxicity. Efforts to improve the outcomes for children with AML should include increased attention to the prevention and mitigation of on-protocol cardiac toxicity. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Genomic epidemiology of methicillin-resistant and -susceptible Staphylococcus aureus from bloodstream infections

BackgroundBloodstream infections due to Staphylococcus aureus cause significant patient morbidity and mortality worldwide. Of major concern is the emergence and spread of methicillin-resistant S. aureus (MRSA) in bloodstream infections, which are associated with therapeutic failure and increased mortality.MethodsWe generated high quality draft genomes from 323 S. aureus blood culture isolates from patients diagnosed with bloodstream infection at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA in 2010–2018.ResultsIn silico detection of antimicrobial resistance genes revealed that 133/323 isolates (41.18%) carry horizontally acquired genes conferring resistance to at least three antimicrobial classes, with resistance determinants for aminoglycosides, beta-lactams and macrolides being the most prevalent. The most common resistance genes were blaZ and mecA, which were found in 262/323 (81.11%) and 104/323 (32.20%) isolates, respectively. Majority of the MRSA (102/105 isolates or 97.14%) identified using in vitro screening were related to two clonal complexes (CC) 5 and 8. The two CCs emerged in the New Hampshire population at separate times. We estimated that the time to the most recent common ancestor of CC5 was 1973 (95% highest posterior density (HPD) intervals: 1966–1979) and 1946 for CC8 (95% HPD intervals: 1924–1959). The effective population size of CC8 increased until the late 1960s when it started to level off until late 2000s. The levelling off of CC8 in 1968 coincided with the acquisition of SCCmec Type IV in majority of the strains. The plateau in CC8 also coincided with the acceleration in the population growth of CC5 carrying SCCmec Type II in the early 1970s, which eventually leveled off in the early 1990s. Lastly, we found evidence for frequent recombination in the two clones during their recent clonal expansion, which has likely contributed to their success in the population.ConclusionsWe conclude that the S. aureus population was shaped mainly by the clonal expansion, recombination and co-dominance of two major MRSA clones in the last five decades in New Hampshire, USA. These results have important implications on the development of effective and robust strategies for intervention, control and treatment of life-threatening bloodstream infections.

Evaluation of Pseudomonas aeruginosa pathogenesis and therapeutics in military-relevant animal infection models.

Modern combat-related injuries are often associated with acute polytrauma. As a consequence of severe combat-related injuries, a dysregulated immune response results in serious infectious complications. The gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen that often causes life-threatening bloodstream, lung, bone, urinary tract, and wound infections following combat-related injuries. The rise in the number of multidrug-resistant P. aeruginosa strains has elevated its importance to civilian clinicians and military medicine. Development of novel therapeutics and treatment options for P. aeruginosa infections is urgently needed. During the process of drug discovery and therapeutic testing, invivo testing in animal models is a critical step in the bench-to-bedside approach, and required for Food and Drug Administration approval. Here, we review current and past literature with a focus on combat injury-relevant animal models often used to understand infection development, the interplay between P. aeruginosa and the host, and evaluation of novel treatments. Specifically, this review focuses on the following animal infection models: wound, burn, bone, lung, urinary tract, foreign body, and sepsis.

Effect of infusion set replacement intervals on catheter-related bloodstream infections (RSVP): a randomised, controlled, equivalence (central venous access device)–non-inferiority (peripheral arterial catheter) trial

The optimal duration of infusion set use to prevent life-threatening catheter-related bloodstream infection (CRBSI) is unclear. We aimed to compare the effectiveness and costs of 7-day (intervention) versus 4-day (control) infusion set replacement to prevent CRBSI in patients with central venous access devices (tunnelled cuffed, non-tunnelled, peripherally inserted, and totally implanted) and peripheral arterial catheters. We did a randomised, controlled, assessor-masked trial at ten Australian hospitals. Our hypothesis was CRBSI equivalence for central venous access devices and non-inferiority for peripheral arterial catheters (both 2% margin). Adults and children with expected greater than 24 h central venous access device-peripheral arterial catheter use were randomly assigned (1:1; stratified by hospital, catheter type, and intensive care unit or ward) by a centralised, web-based service (concealed before allocation) to infusion set replacement every 7 days, or 4 days. This included crystalloids, non-lipid parenteral nutrition, and medication infusions. Patients and clinicians were not masked, but the primary outcome (CRBSI) was adjudicated by masked infectious diseases physicians. The analysis was modified intention to treat (mITT). This study is registered with the Australian New Zealand Clinical Trials Registry ACTRN12610000505000 and is complete. Between May 30, 2011, and Dec, 9, 2016, from 6007 patients assessed, we assigned 2944 patients to 7-day (n=1463) or 4-day (n=1481) infusion set replacement, with 2941 in the mITT analysis. For central venous access devices, 20 (1·78%) of 1124 patients (7-day group) and 16 (1·46%) of 1097 patients (4-day group) had CRBSI (absolute risk difference [ARD] 0·32%, 95% CI -0·73 to 1·37). For peripheral arterial catheters, one (0·28%) of 357 patients in the 7-day group and none of 363 patients in the 4-day group had CRBSI (ARD 0·28%, -0·27% to 0·83%). There were no treatment-related adverse events. Infusion set use can be safely extended to 7 days with resultant cost and workload reductions. Australian National Health and Medical Research Council.

Exploring Candida auris in its habitat

Candida auris colonizes human skin and causes life-threatening fungal bloodstream infections. In this issue of Cell Host & Microbe, Huang etal. introduce a murine model of C.auris skin colonization to explore the role of distinct clades, immune signaling pathways, antibiotics, and disinfectants on fungal persistence in or clearance from its habitat.

Distribution of Yeast Species Isolated from Blood Cultures for a Six Year Period in Turkey: a Multicentre Study

Bloodstream infections due to yeast species especially Candida spp. have been reported to be important healthcare associated infections with high mortality and morbidity rates. Candidemia causes prolonged hospital stays as well as increased cost. In order to prevent or treat these life-threatening bloodstream infections successfully, nationwide epidemiological data should be available about the etiological agents of these infections. Multi-centre national epidemiological data on yeast bloodstream infections in Turkey is lacking. A retrospective study was designed and data from six different centres in Turkey between 2011 and 2016 years were gathered and analysed for the distribution and frequency of yeast species in order to assist clinicians in their choice of early and appropriate antifungal therapy. All laboratories used automated blood culture systems for the isolation of blood strains. All the participating centres performed the identification of their own isolates by conventional methods using germ tube test, morphology on corn meal agar with tween 80 and chromogenic media and the identification was confirmed by API 20C AUX, API ID 32C or matrix-assisted laser desorption/ionization time of flight mass spectrophotometry (MALDI-TOF MS) systems. The analysis of the results was performed on the basis of intensive care units (ICUs), other inpatient clinics (OICs) and totally all clinics (ACs). Totally 2547 yeast isolates were determined from six participating centres during six years. According to the total ACs results, Candida albicans was the most prevalent species (43.1%), followed by Candida parapsilosis complex (29.1%), Candida glabrata (10.1%), Candida tropicalis (7.5%), Candida krusei (2.4%) and Candida kefyr (1.6%) and the remaining (6.2%) of them consisted of other yeast species. The distribution of the Candida species did not show statistically significant difference between the years, however the increase of C.parapsilosis complex in 2016 was statistically significant, (p= 0.02). During the study period, totally 1054 yeast isolates were obtained from the ICUs of the centres. C.albicans predominated with 476 (45.2%) isolates and C.parapsilosis complex (28.7%), C.glabrata (10.7%) and C.tropicalis (7.3%) were the other leading species in ICUs. Among 1493 isolates of the OICs of six centres participated in the study, C.albicans was the most prevalent species with 622 (41.7%) isolates. The other frequent species of OICs were C.parapsilosis complex (29.5%), C.glabrata (9.6%) and C.tropicalis (7.6%) resembling ICU results. It can be concluded that C.albicans is still the leading cause of bloodstream infections in the six different centres located in various geographical areas of Turkey.

An analysis of totally implantable central venous port system infections in an urban tertiary referral center

A frequent complication of central venous port systems (CVP) is infection (CVP-I), either local (CVP-LI) or a life-threatening blood stream infection (CVP-BSI). We examined the course of CVP-I including results of an antibiotic eradication attempt of CVP-BSI. We investigated adults with CVP-I from 2010 to 2018 who had to undergo port explantation or were treated by a combination of systemic antibiotics and antibiotic lock therapy (ALT). In nine years we diagnosed 206 CVP-I (CVP-LI: 52; CVP-BSI: 152). In 146 patients with CVP-I the port system was primary explanted, while 56 patients received antibiotics/ALT. 79% of Gram negative pathogens and 50% of coagulase negative staphylococci (CoNS) were eradicated. Failure of antibiotic treatment was more often associated with short time span since CVP implantation, neutropenia and polymicrobial infection. All patients with non-neoplastic disease survived, while 18/173 patients (10%) with underlying malignant disease had a fatal outcome in the same hospital stay.

Virulence phenotypes result from interactions between pathogen ploidy and genetic background.

Studying fungal virulence is often challenging and frequently depends on many contexts, including host immune status and pathogen genetic background. However, the role of ploidy has often been overlooked when studying virulence in eukaryotic pathogens. Since fungal pathogens, including the human opportunistic pathogen Candida albicans, can display extensive ploidy variation, assessing how ploidy impacts virulence has important clinical relevance. As an opportunistic pathogen, C. albicans causes nonlethal, superficial infections in healthy individuals, but life‐threatening bloodstream infections in individuals with compromised immune function. Here, we determined how both ploidy and genetic background of C. albicans impacts virulence phenotypes in healthy and immunocompromised nematode hosts by characterizing virulence phenotypes in four near‐isogenic diploid and tetraploid pairs of strains, which included both laboratory and clinical genetic backgrounds. We found that C. albicans infections decreased host survival and negatively impacted host reproduction, and we leveraged these two measures to survey both lethal and nonlethal virulence phenotypes across the multiple C. albicans strains. In this study, we found that regardless of pathogen ploidy or genetic background, immunocompromised hosts were susceptible to fungal infection compared to healthy hosts. Furthermore, for each host context, we found a significant interaction between C. albicans genetic background and ploidy on virulence phenotypes, but no global differences between diploid and tetraploid pathogens were observed.

Policy and Pandemic: The Changing Practice of Nephrology During the Coronavirus Disease-2019 Outbreak.

The coronavirus (coronavirus disease-2019) pandemic has changed care delivery for patients with end-stage kidney disease. We explore the US healthcare system as it pertains to dialysis care, including existing policies, modifications implemented in response to the coronavirus disease-2019 crisis, and possible next steps for policy makers and nephrologists. This includes policies related to resource management, use of telemedicine, prioritization of dialysis access procedures, expansion of home dialysis modalities, administrative duties, and quality assessment. The government has already established policies that have instated some flexibilities to help providers focus their response to the crisis. However, future policy during and after the coronavirus disease-2019 pandemic can bolster our ability to optimize care for patients with end-stage kidney disease. Key themes in this perspective are the importance of policy flexibility, clear strategies for emergency preparedness, and robust health systems that maximize accessibility and patient autonomy.

Reduction of Pathogen Load From the Blood in Septic Patients With Suspected, Life-threatening Bloodstream Infection

Reduction of Pathogen Load From the Blood in Septic Patients With Suspected, Life-threatening Bloodstream Infection

The Synergism of the Small Molecule ENOblock and Fluconazole Against Fluconazole-Resistant Candida albicans.

Candida albicans is the most common opportunistic fungal pathogen which can cause life-threatening bloodstream infections known as candidaemia. It is very important to discover new drugs and targets for the treatment of candidaemia. In this study, we first investigated the combination antifungal effects of the small molecule ENOblock and fluconazole (FLC) against FLC-resistant C. albicans. A checkerboard microdilution assay showed that ENOblock has a significant synergistic effect in combination with FLC against FLC-resistant C. albicans. The time-kill curve further confirmed the synergism of this compound with FLC against FLC-resistant C. albicans. Moreover, we demonstrated the significant inhibitory effects of ENOblock alone and in combination with FLC against C. albicans hypha and biofilm formation. Furthermore, the XTT assay showed that ENOblock has relatively low toxicity to human umbilical vein endothelial cells. The in vivo antifungal efficacy of ENOblock was further assessed in a murine model of systemic C. albicans infection. Although ENOblock alone was not sufficient to treat C. albicans infection, the combination of FLC and ENOblock showed significant in vivo activity against FLC-resistant C. albicans. Finally, using surface plasmon resonance analysis as well as an inhibition assay, we determined that ENOblock directly interacted with CaEno1 and significantly inhibited the transglutaminase activity of this enzyme, which is involved in the growth and morphogenesis of C. albicans. In summary, these results demonstrate the synergistic effects of FLC and ENOblock against FLC-resistant C. albicans, and indicate that inhibition of the transglutaminase activity of CaEno1 by ENOblock might confer an advantage for the synergism of FLC and ENOblock, suggesting the potential of ENOblock as a new antifungal candidate.

Non detection of &lt;i&gt;mecA&lt;/i&gt; gene in methicillin resistant &lt;i&gt;Staphylococcus aureus&lt;/i&gt; isolates from pigs

Background: Methicillin resistant Staphylococcus aureus (MRSA) have become a global health problem causing infections in both humans and livestock, ranging from skin and soft tissue to life threatening blood stream infections. The mecA gene is known to confer resistance to MRSA isolates. This study investigated the carriage of mecA gene by MRSA isolates from pigs.Methods: One hundred non duplicate staphylococcal isolates recovered from blood samples of pigs in Bariga district of Lagos State at the Molecular Biology and Biotechnology unit of the Nigerian Institute of Medical Research were used in the study. S. aureus was identified by cultural characteristics, and positive catalase, coagulase and deoxyribonuclease tests. Phenotypic methicillin resistance was determined by the modified Kirby Bauer disk diffusion method and mecA gene was detected by conventional polymerase chain reaction (PCR) assay.Results: Twenty-five S. aureus were identified, of which 11 (44%) were MRSA by phenotypic method. All the isolates were mecA negative on PCR.Conclusion: The MRSA phenotype observed in the pig isolates in this study appears not to be the classical mecA mediated resistance. There may be alternative mechanisms of resistance in MRSA isolates in pigs.Keywords: MRSA, phenotypic, mecA gene, PCR, pigs

Candida glabrata: A Lot More Than Meets the Eye

Candida glabrata is an opportunistic human fungal pathogen that causes superficial mucosal and life-threatening bloodstream infections in individuals with a compromised immune system. Evolutionarily, it is closer to the non-pathogenic yeast Saccharomyces cerevisiae than to the most prevalent Candida bloodstream pathogen, C. albicans. C. glabrata is a haploid budding yeast that predominantly reproduces clonally. In this review, we summarize interactions of C. glabrata with the host immune, epithelial and endothelial cells, and the ingenious strategies it deploys to acquire iron and phosphate from the external environment. We outline various attributes including cell surface-associated adhesins and aspartyl proteases, biofilm formation and stress response mechanisms, that contribute to the virulence of C. glabrata. We further discuss how, C. glabrata, despite lacking morphological switching and secreted proteolytic activity, is able to disarm macrophage, dampen the host inflammatory immune response and replicate intracellularly.

1756. Prediction of Bloodstream Infection Prior to Onset of Symptoms by Plasma Metagenomic Sequencing in Pediatric Patients With Relapsed or Refractory Malignancy (PREDSEQ)

BackgroundPatients undergoing treatment for relapsed or refractory malignancies are at high risk of life-threatening bloodstream infection (BSI). A predictive screening test for BSI might allow pre-emptive therapy, but no validated test is currently available. We tested the hypothesis that plasma metagenomic next generation pathogen sequencing (NGS) would predict BSI before the onset of attributable symptoms.MethodsWe enrolled 31 pediatric patients receiving for treatment relapsed or refractory malignancy in an IRB-approved prospective cohort study (PREDSEQ) of predictive sequencing. Episodes of febrile neutropenia or documented infection were collected prospectively from the medical record. BSI was defined according to NHSN criteria. Control Samples were defined as samples collected ≥7 clear days before or after any fever or documented infection. Residual clinical samples were stored for NGS; after filtering human sequences, reads were aligned to a curated pathogen database, and organisms above a predefined threshold were reported (Karius Inc., Redwood City, CA). Only bacteria and fungi were included in this analysis.ResultsA total of 11 BSI episodes occurred in 9 participants (Table 1) during the study period. Predictive sensitivity of NGS in the 2 days before onset of infection (n = 9) was 78% (95% CI 45–94%), and diagnostic sensitivity on the day of infection (n = 11) was 82% (95% CI 52–95%). Specificity of NGS for development of fever or infection within 7 days (n = 16) was 81% (95% CI 57–93%). NGS was positive up to 6 days prior to onset of BSI. In samples collected before or during documented infections, NGS also identified additional bacteria and fungi that were not detected by standard clinical testing.ExpectedNGS PredictionNGS DiagnosisAdditional OrganismsBSI√√No1 S. epidermidis √√No2 E. coli √√Yes3 E. faecium √√Yes4 E. faecium √√Yes5 R. mucilaginosa √√Yes6 S. epidermidis √√Yes7 E. coli/R. mucilaginosa √√Yes8 E. coli XXYes9 C. kruzei XXYes10 S. epidermidis N/A√No11 C. jeikeium N/A√YesControl1N/AN/AN/A V. parvula 2N/AN/AN/A F. magna 3N/AN/AN/A H. pylori and L. fermentum4–10N/AN/AN/ANoConclusionPlasma NGS shows promise for the detection of BSI prior to onset of symptoms in high-risk patients.Disclosures K. Goggin, Karius Inc.: Investigator, Research support. K. L. Chan, Karius Inc.: Employee, Salary. D. Hollemon, Karius Inc.: Employee, Salary. A. Ahmed, Karius, Inc.: Employee, Salary. D. Hong, Karius, Inc.: Employee, Salary. R. Hayden, Roche Molecular: Scientific Advisor, Consulting fee. Abbott Molecular: Scientific Advisor, Consulting fee. Quidel: Scientific Advisor, Consulting fee. C. Gawad, Karius Inc.: Investigator, Research support. J. Wolf, Karius Inc.: Investigator, Research support.

Deletion of GLX3 in Candida albicans affects temperature tolerance, biofilm formation and virulence.

Candida albicans is a predominant cause of fungal infections in mucosal tissues as well as life-threatening bloodstream infections in immunocompromised patients. Within the human body, C. albicans is mostly embedded in biofilms, which provides increased resistance to antifungal drugs. The glyoxalase Glx3 is an abundant proteomic component of the biofilm extracellular matrix. Here, we document phenotypic studies of a glx3Δ null mutant concerning its role in biofilm formation, filamentation, antifungal drug resistance, cell wall integrity and virulence. First, consistent with its function as glyoxalase, the glx3 null mutant showed impaired growth on media containing glycerol as the carbon source and in the presence of low concentrations of hydrogen peroxide. Importantly, the glx3Δ mutant showed decreased fitness at 37°C and formed less biofilm as compared to wild type and a reintegrant strain. At the permissive temperature of 28°C, the glx3Δ mutant showed impaired filamentation as well as increased sensitivity to Calcofluor white, Congo red, sodium dodecyl sulfate and zymolyase, indicating subtle alterations in wall architecture even though gross quantitative compositional changes were not detected. Interestingly, and consistent with its impaired filamentation, biofilm formation and growth at 37°C, the glx3Δ mutant is avirulent. Our results underline the role of Glx3 in fungal pathogenesis and the involvement of the fungal wall in this process.

Echinocandin-Induced Microevolution of Candida parapsilosis Influences Virulence and Abiotic Stress Tolerance.

Candida species are a major cause of life-threatening bloodstream infections worldwide. Although Candida albicans is responsible for the vast majority of infections, the clinical relevance of other Candida species has also emerged over the last twenty years. This shift might be due in part to changes in clinical guidelines, as echinocandins became the first line of therapeutics for the treatment. Candida parapsilosis is an emerging non-albicans Candida species that exhibits lower susceptibility levels to these drugs. Candida species frequently display resistance to echinocandins, and the mechanism for this is well-known in C. albicans and Candida glabrata, where it is mediated by amino acid substitutions at defined locations of the β-1,3-glucan synthase, Fks1p. In C. parapsilosis isolates, Fks1p harbors an intrinsic amino acid change at position 660 of the hot spot 1 (HS1) region, which is thought to be responsible for the high MIC values. Less is known about acquired substitutions in this species. In this study, we used directed evolution experiments to generate C. parapsilosis strains with acquired resistance to caspofungin, anidulafungin, and micafungin. We showed that cross-resistance was dependent on the type of echinocandin used to generate the evolved strains. During their characterization, all mutant strains showed attenuated virulence in vivo and also displayed alterations in the exposure of inner cell wall components. The evolved strains harbored 251 amino acid changes, including three in the HS1, HS2, and HS3 regions of Fks1p. Altogether, our results demonstrate a direct connection between acquired antifungal resistance and virulence of C. parapsilosisIMPORTANCECandida parapsilosis is an opportunistic fungal pathogen with the ability to cause infections in immunocompromised patients. Echinocandins are the currently recommended first line of treatment for all Candida species. Resistance of Candida albicans to this drug type is well characterized. C. parapsilosis strains have the lowest in vitro susceptibility to echinocandins; however, patients with such infections typically respond well to echinocandin therapy. There is little knowledge of acquired resistance in C. parapsilosis and its consequences on other characteristics such as virulence properties. In this study, we aimed to dissect how acquired echinocandin resistance influences the pathogenicity of C. parapsilosis and to develop explanations for why echinocandins are clinically effective in the setting of acquired resistance.

Competition of Candida glabrata against Lactobacillus is Hog1 dependent.

Candida glabrata is a common human fungal commensal and opportunistic pathogen. This fungus shows remarkable resilience as it can form recalcitrant biofilms on indwelling catheters, has intrinsic resistance against azole antifungals, and is causing vulvovaginal candidiasis. As a nosocomial pathogen, it can cause life‐threatening bloodstream infections in immune‐compromised patients. Here, we investigate the potential role of the high osmolarity glycerol response (HOG) MAP kinase pathway for C. glabrata virulence. The C. glabrata MAP kinase CgHog1 becomes activated by a variety of environmental stress conditions such as osmotic stress, low pH, and carboxylic acids and subsequently accumulates in the nucleus. We found that CgHog1 allows C. glabrata to persist within murine macrophages, but it is not required for systemic infection in a mouse model. C. glabrata and Lactobacilli co‐colonise mucosal surfaces. Lactic acid at a concentration produced by vaginal Lactobacillus spp. causes CgHog1 phosphorylation and accumulation in the nucleus. In addition, CgHog1 enables C. glabrata to tolerate different Lactobacillus spp. and their metabolites when grown in co‐culture. Using a phenotypic diverse set of clinical C. glabrata isolates, we find that the HOG pathway is likely the main quantitative determinant of lactic acid stress resistance. Taken together, our data indicate that CgHog1 has an important role in the confrontation of C. glabrata with the common vaginal flora.

Urgent: Stop Preventable Infections Now.

In 2009, the US Renal Data System (USRDS) presented trends in rates of hospitalization for cardiovascular disease and infection in the first year of dialysis, 1991–2006 ([1][1]), highlighting a marked rise in infection-related hospitalizations and a need for providers and policymakers to address

A pilot study for evaluation of knowledge and common practises of nursing staff regarding use of multidose injection vials and their microbial contamination rate in a super-specialty hospital.

CONTEXT:Multidose injection vials (MDVs) are prone to bacterial contamination, and their use has been reported to be a potential source of infections.AIMS:The aim of this study was to evaluate the knowledge and common practises of nursing staff regarding the use of MDVs and its microbial contamination rate.SETTINGS AND DESIGN:A pilot study was conducted in a super-specialty hospital from June to December 2016.SUBJECTS AND METHODS:Information about knowledge and common practises of 100 nursing staff posted in various Intensive Care Units (ICUs) with respect to the usage of single and MDVs, respectively, was obtained and assessed. About 40 in-use multidose injection vials containing some remnants were collected from different ICUs. The volume of 1 ml content of each of these vials was inoculated into a tube containing 15 ml thioglycolate broth and incubated at 37°C for 10 days. The broth was visually examined every day and subcultured onto blood, chocolate, and Sabouraud Dextrose agar plates on alternate days within 10 days or any time that the appearance seemed turbid. The microbial isolates thus obtained were identified using standard guidelines and recorded.STATISTICAL ANALYSIS USED:Descriptive statistics were used.RESULTS:The study group members had sufficient knowledge about various aspects of handling single and MDVs, respectively, such as hand hygiene, disinfection, checking of vial labels, and expiry date. Low hand hygiene compliance rate of 55% was observed in all ICUs visited during this study. The contamination rate of MDVs injection vials was 25% with Coagulase-negative Staphylococcus spp. being the most common isolate.CONCLUSIONS:The use of MDVs is associated with the risk of contamination and nosocomial outbreaks of life-threatening bloodstream infections. Healthcare professionals must strictly adhere to basic infection control practises as per standard guidelines to minimize the incidence of hospital-acquired infections.

Microbe Profile: Candida albicans: a shape-changing, opportunistic pathogenic fungus of humans.

Candida albicans is normally a harmless commensal of human beings, but it can cause superficial infections of the mucosa (oral/vaginal thrush) in healthy individuals and (rarely) infections of the skin or nails. It can also become invasive, causing life-threatening systemic and bloodstream infections in immunocompromised hosts, where the mortality rate can be as high as 50 %. It is the most common cause of serious fungal infection and is a common cause of nosocomial infections in hospitals. Some strains have been recognized that are resistant to azoles or echinocandins, which are the first-line antifungals for treatment of C. albicans infections.