Emergence of non-susceptibility during persistent Pseudomonas aeruginosa bacteraemia in haematopoietic cell transplant recipients and haematological malignancy patients
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ABSTRACT: Background
Systematic studies pertaining to the emergence of resistance during therapy
SUBMITTER: Fontana L
PROVIDER: S-EPMC8519295 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:An epidemiological study uncovered that fluoroquinolone (FQ) neutropenic prophylaxis in hematopoietic cell transplant and hematologic malignancy (HCT/HM) patients was associated with breakthrough Pseudomonas aeruginosa bloodstream infections (BSIs) with isolates non-susceptible to both FQs and meropenem. The molecular epidemiology of the FQ/meropenem-non-susceptible P. aeruginosa isolates causing FQ-breakthrough BSIs in the HCT/HM patients remains unclear. Through whole genome sequencing on 57 P. aeruginosa isolates from 54 patients diagnosed with HM or receiving an HCT, we found that ST111 strains predominated, accounting for 22 (38.6%) of the isolates. 17 of 33 (51.5%) FQ-breakthrough BSIs were caused by ST111 strains, of which 15 (88.2%) were meropenem non-susceptible. ST111 strains, but not other oprD-deficient, meropenem-non-susceptible clinical strains, were found to have a colonization advantage over P. aeruginosa strain PA14 in C. elegans and to outcompete PA14 in in vitro co-culture assays. Together, we found that breakthrough P. aeruginosa BSIs during FQ prophylaxis in HCT/HM patients are dominated by clonally-related FQ/meropenem non-susceptible strains, predominantly ST111 type, and that the dominance of ST111 strains may be explained by a relative fitness advantage over other clinical strains. Additional work is necessary to better understand the factors driving the dominance and persistence of these ST111 strains.
| S-EPMC9244782 | biostudies-literature
Project description: Not available
| S-EPMC6353308 | biostudies-literature
Project description:Recipients of a haematopoietic stem cell transplantation (HSCT) may experience issues in medication adherence (MA) when discharged. The primary aim of this review was to describe the oral MA prevalence and the tools used to evaluate it among these patients; the secondary aims were to summarise factors affecting medication non-adherence (MNA), interventions promoting MA, and outcomes of MNA. A systematic review (PROSPERO no. CRD42022315298) was performed by searching the Cumulative Index of Nursing and Allied Health (CINAHL), Cochrane Library, Excerpta Medica dataBASE (EMBASE), PsycINFO, PubMed and Scopus databases, and grey literature up to May 2022 by including (a) adult recipients of allogeneic HSCT, taking oral medications up to 4 years after HSCT; (b) primary studies published in any year and written in any language; (c) with an experimental, quasi-experimental, observational, correlational, and cross-sectional design; and (d) with a low risk of bias. We provide a qualitative narrative synthesis of the extracted data. We included 14 studies with 1049 patients. The median prevalence of MA was 61.8% and it has not decreased over time (immunosuppressors 61.5% [range 31.3-88.8%] and non-immunosuppressors 65.2% [range 48-100%]). Subjective measures of MA have been used most frequently (78.6%) to date. Factors affecting MNA are younger age, higher psychosocial risk, distress, daily immunosuppressors, decreased concomitant therapies, and experiencing more side effects. Four studies reported findings about interventions, all led by pharmacists, with positive effects on MA. Two studies showed an association between MNA and chronic graft-versus-host disease. The variability in adherence rates suggests that the issues are relevant and should be carefully considered in daily practice. MNA has a multifactorial nature and thus requires multidisciplinary care models.
| S-EPMC10177142 | biostudies-literature
Project description:BackgroundIn Pseudomonas aeruginosa, fluoroquinolone exposure promotes resistance to carbapenems through upregulation of efflux pumps and transcriptional downregulation of the porin OprD. Evidence of this effect among hematologic malignancy (HM) patients or hematopoietic cell transplant (HCT) recipients receiving fluoroquinolone prophylaxis for neutropenia is lacking.MethodsWe retrospectively evaluated episodes of P. aeruginosa bloodstream infections in HM patients or HCT recipients over a 7-year period at our institution. We determined the association of fluoroquinolone prophylaxis at the time of infection with meropenem susceptibility of P. aeruginosa breakthrough isolates and risk factors for meropenem nonsusceptibility. Whole-genome sequencing (WGS) and phenotypic assessments of meropenem efflux pump activity were performed on select isolates to determine the mechanisms of meropenem resistance.ResultsWe analyzed 55 episodes of P. aeruginosa bacteremia among 51 patients. Breakthrough bacteremia while on fluoroquinolone prophylaxis was associated with nonsusceptibility to meropenem, but not to antipseudomonal β-lactams or aminoglycosides. The receipt of fluoroquinolone prophylaxis was independently predictive of bacteremia with a meropenem-nonsusceptible isolate. All meropenem-nonsusceptible isolates analyzed by WGS contained oprD inactivating mutations, and all meropenem-nonsusceptible isolates tested demonstrated reductions in the meropenem minimum inhibitory concentration in the presence of an efflux pump inhibitor. A phylogenetic analysis based on WGS revealed several clusters of closely related isolates from different patients.ConclusionsFluoroquinolone prophylaxis in HM patients and HCT recipients is associated with breakthrough bacteremia with meropenem-nonsusceptible P. aeruginosa strains, likely due to both mutations increasing efflux pump activity and the epidemiology of P. aeruginosa bloodstream infections in our patient population.
| S-EPMC6541707 | biostudies-literature
Project description:IntroductionPatients receiving a haematopoietic stem cell transplant (HSCT) are subjected to complex oral medications based on prophylactic and immunosuppressive treatments. Adherence to medication plays a role in survival, and medication non-adherence (MNA) is closely associated with graft-versus-host disease and other complications. The aim of this systematic review is to summarise the available evidence regarding prevalence rates of medication adherence, the risk factors of MNA, the effectiveness of interventions to increase medication adherence and the outcomes associated with MNA.Methods and analysisWe designed a systematic review according to the Joanna Briggs Institute methodology. We will search the Cochrane Library and the CINAHL, EMBASE, MEDLINE via PubMed, PsycINFO and Scopus databases. We will include published and unpublished primary studies: (a) on humans, from inception until 10 May 2022; (b) written in any language; (c) experimental (randomised and non-randomised), observational (prospective, retrospective cohort and case-control), correlational, cross-sectional and longitudinal; and (d) with a low risk of bias, according to the quality assessment we perform. We will exclude secondary and qualitative studies, protocols, publications without original data, including paediatrics or related to autologous HSCT. The primary outcome will be the prevalence of oral medication adherence; the secondary outcomes will be the risk factors of MNA, the interventions aimed at increasing medication adherence and the outcomes of MNA. Two researchers will independently screen the eligible studies, then extract and describe the data. Disagreements will be resolved by a third researcher. We will provide a qualitative narrative synthesis of the findings.Ethics and disseminationEthical approval is not required given that previously published studies will be used. We will disseminate the findings through conference presentations and publications in international peer-reviewed scientific journals.Prospero registration numberCRD42022315298.
| S-EPMC9717329 | biostudies-literature
Project description:BackgroundAscertainment of cases and disease classification is an acknowledged problem for epidemiological research into haematological malignancies.MethodsThe Haematological Malignancy Research Network comprises an ongoing population-based patient cohort. All diagnoses (paediatric and adult) across two UK Cancer Networks (population 3.6 million, >2000 diagnoses annually, socio-demographically representative of the UK) are made by an integrated haematopathology laboratory. Diagnostics, prognostics, and treatment are recorded to clinical trial standards, and socio-demographic measures are routinely obtained.ResultsA total of 10,729 haematological malignancies (myeloid=2706, lymphoid=8023) were diagnosed over the 5 years, that is, from 2004 to 2009. Descriptive data (age, sex, and deprivation), sex-specific age-standardised (European population) rates, and estimated UK frequencies are presented for 24 sub-types. The age of patients ranged from 4 weeks to 99 years (median 70.6 years), and the male rate was more than double the female rate for several myeloid and lymphoid sub-types, this difference being evident in both children and adults. No relationship with deprivation was detected.ConclusionAccurate population-based data on haematological malignancies can be collected to the standard required to deliver reproducible results that can be extrapolated to national populations. Our analyses emphasise the importance of gender and age as disease determinants, and suggest that aetiological investigations that focus on socio-economic factors are unlikely to be rewarding.
| S-EPMC3242607 | biostudies-literature
Project description:New mutations conferring resistance to SARS-CoV-2 therapeutics have important clinical implications. We describe the first cases of an independently acquired V792I RNA-dependent RNA polymerase mutation developing in renal transplant recipients after remdesivir exposure. Our work underscores the need for augmented efforts to identify concerning mutations and address their clinical implications.
| S-EPMC9619446 | biostudies-literature
Project description:Up-to-date information on coronavirus disease 2019 (COVID-19) outcomes and risk factors in haematopoietic cell transplantation (HCT) recipients is required to inform on decisions about cancer treatment and COVID-19 mitigation strategies. We performed a meta-analysis to address this knowledge gap. All studies with at least five patients who reported COVID-19-related deaths in HCT recipients were included. The primary outcome was COVID-19-related death. Secondary outcomes were COVID-19-related mechanical ventilation (MV) and intensive care unit (ITU) admission. The cumulative COVID-19-related death rate among HCT recipients was 21% (95% confidence interval [CI] 18%-24%), while MV and ITU admission rates were 14% (95% CI 11%-17%) and 18% (95% CI 14%-22%), respectively. Subgroup analysis showed higher death rates in patients who developed COVID-19 within 12 months of HCT (risk ratio [RR] 1.82, 95% CI 1.09-3.03), within 6 months of receiving immunosuppressant drugs (RR 2.11, 95% CI 1.38-3.20) or in the context of active graft-versus-host disease (RR 2.38, 95% CI 1.10-5.16). Our findings support the idea that HCT should remain an integral part of cancer treatment during the COVID-19 pandemic but also highlight the need to prioritise preventative measures in those patients who are at increased risk of adverse COVID-19 outcomes.
| S-EPMC9350043 | biostudies-literature
Project description:Pseudomonas aeruginosa (P. aeruginosa) is one of the most common nosocomial pathogens worldwide. Although the emergence of multidrug-resistant (MDR) P. aeruginosa is a critical problem in medical practice, the key features involved in the emergence and spread of MDR P. aeruginosa remain unknown. This study utilized whole genome sequence (WGS) analyses to define the population structure of 185 P. aeruginosa clinical isolates from several countries. Of these 185 isolates, 136 were categorized into sequence type (ST) 235, one of the most common types worldwide. Phylogenetic analysis showed that these isolates fell within seven subclades. Each subclade harbors characteristic drug resistance genes and a characteristic genetic background confined to a geographic location, suggesting that clonal expansion following antibiotic exposure is the driving force in generating the population structure of MDR P. aeruginosa. WGS analyses also showed that the substitution rate was markedly higher in ST235 MDR P. aeruginosa than in other strains. Notably, almost all ST235 isolates harbor the specific type IV secretion system and very few or none harbor the CRISPR/CAS system. These findings may help explain the mechanism underlying the emergence and spread of ST235 P. aeruginosa as the predominant MDR lineage.
| S-EPMC5726472 | biostudies-literature
Project description:RationalePseudomonas aeruginosa is one of the leading causes of gram-negative ventilator-associated pneumonia (VAP) associated with a mortality rate of 34 to 68%. Recent evidence suggests that P. aeruginosa in patients with VAP may persist in the alveolar space despite adequate antimicrobial therapy. We hypothesized that failure to eradicate P. aeruginosa from the lung is linked to type III secretory system (TTSS) isolates.ObjectivesTo determine the mechanism by which infection with P. aeruginosa in patients with VAP may evade the host immune response.MethodsThirty-four patients with P. aeruginosa VAP underwent noninvasive bronchoalveolar lavage (BAL) at the onset of VAP and on Day 8 after initiation of antibiotic therapy. Isolated pathogens were analyzed for secretion of type III cytotoxins. Neutrophil apoptosis in BAL fluid was quantified by assessment of nuclear morphology on Giemsa-stained cytocentrifuge preparations. Neutrophil elastase was assessed by immunoenzymatic assay.Measurements and main resultsTwenty-five out of the 34 patients with VAP secreted at least one of type III proteins. There was a significant difference in apoptotic rate of neutrophils at VAP onset between those strains that secreted cytotoxins and those that did not. Neutrophil elastase levels were positively correlated with the rate of apoptosis (r = 0.43, P < 0.01). Despite adequate antimicrobial therapy, 13 out of 25 TTSS(+) isolates were recovered at Day 8 post-VAP, whereas eradication was achieved in all patients who had undetectable levels of type III secretion proteins.ConclusionsThe increased apoptosis in neutrophils by the TTSS(+) isolates may explain the delay in eradication of Pseudomonas strains in patients with VAP. Short-course antimicrobial therapy may not be adequate in clearing the infection with a TTSS secretory phenotype.
| S-EPMC2542430 | biostudies-literature