Modifiable Risk Factors for the Emergence of Ceftolozane-tazobactam Resistance

Abstract Background Ceftolozane-tazobactam (TOL-TAZ) affords broad coverage against Pseudomonas aeruginosa. Regrettably, TOL-TAZ resistance has been reported. We sought to identify modifiable risk factors that may reduce the emergence of TOL-TAZ resistance. Methods Twenty-eight consecutive patients infected with carbapenem-resistant P. aeruginosa isolates susceptible to TOL-TAZ, treated with ≥72 hours of TOL-TAZ , and with P. aeruginosa isolates available both before and after TOL-TAZ exposure between January 2018 and December 2019 in Baltimore, Maryland, were included. Cases were defined as patients with at least a 4-fold increase in P. aeruginosa TOL-TAZ MICs after exposure to TOL-TAZ. Independent risk factors for the emergence of TOL-TAZ resistance comparing cases and controls were investigated using logistic regression. Whole genome sequencing of paired isolates was used to identify mechanisms of resistance that emerged during TOL-TAZ therapy. Results Fourteen patients (50%) had P. aeruginosa isolates which developed at least a 4-fold increase in TOL-TAZ MICs(ie, cases). Cases were more likely to have inadequate source control (29% vs 0%, P = .04) and were less likely to receive TOL-TAZ as an extended 3-hour infusion (0% vs 29%; P = .04). Eighty-six percent of index isolates susceptible to ceftazidime-avibactam (CAZ-AVI) had subsequent P. aeruginosa isolates with high-level resistance to CAZ-AVI, after TOL-TAZ exposure and without any CAZ-AVI exposure. Common mutations identified in TOL-TAZ resistant isolates involved AmpC, a known binding site for both ceftolozane and ceftazidime, and DNA polymerase. Conclusions Due to our small sample size, our results remain exploratory but forewarn of the potential emergence of TOL-TAZ resistance during therapy and suggest extending TOL-TAZ infusions may be protective. Larger studies are needed to investigate this association.

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Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients With Carbapenem-Resistant Acinetobacter baumannii Bacteremia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa378 ◽

2020 ◽

Vol 7 (10) ◽

Author(s):

Hyo-Ju Son ◽

Eun Been Cho ◽

Moonsuk Bae ◽

Seung Cheol Lee ◽

Heungsup Sung ◽

...

Keyword(s):

Risk Factors ◽

Acinetobacter Baumannii ◽

Multivariable Analysis ◽

Tertiary Hospital ◽

Source Control ◽

Microbiological Analysis ◽

Clinical Factors ◽

Carbapenem Resistant ◽

Infection Source ◽

Independent Risk Factors

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is associated with significant mortality, causing worldwide concern, yet there are limited data on contributing microbiological factors. This study aimed to identify the clinical and microbiologic risk factors for mortality in CRAB bacteremia. Methods Adult patients with monomicrobial CRAB bacteremia in a 2700-bed tertiary hospital between December 2012 and December 2018 were retrospectively enrolled. Risk factors for 30-day mortality were evaluated. All isolates collected on the first day of bacteremia were subjected to colistin susceptibility testing by broth microdilution and to genotyping by multilocus sequence typing. Results A total of 164 patients were enrolled, and 90 (55%) died within 30 days. The most common genotype among the isolates was ST191 (49%), and 12 isolates (7%) were resistant to colistin. Genotype, colistin minimum inhibitory concentration, and colistin resistance were not significantly associated with mortality, in contrast to several clinical factors. In multivariable analysis, ineradicable or not-eradicated focus (adjusted odds ratio [aOR], 4.92; 95% CI, 1.95–12.42; P = .001), septic shock (aOR, 4.72; 95% CI, 2.12–10.49; P < .001), and inappropriate antimicrobial therapy (aOR, 2.54; 95% CI, 1.05–6.16; P = .04) were independent risk factors for mortality. Among antibiotic strategies, colistin combined with tigecycline or other antibiotics were significantly associated with lower mortality after adjustment for confounding factors. Conclusions Clinical factors such as the nature of the infection source and source control, severity of bacteremia, and appropriateness of antibiotics, rather than microbiological factors, contribute to mortality in CRAB bacteremia. A specific antibiotic combination may help improve outcomes.

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518. Comparing the Mortality of Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.587 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S249-S250

Author(s):

Hyeonji Seo ◽

Eunmi Yang ◽

Seongman Bae ◽

Hyemin Chung ◽

Eunbeen Cho ◽

...

Keyword(s):

Risk Factors ◽

Combination Therapy ◽

Resistance Mechanism ◽

Carbapenem Resistance ◽

Source Control ◽

Definitive Treatment ◽

Clinical Issue ◽

Carbapenem Resistant ◽

Independent Risk Factors ◽

Carbapenem Resistant Enterobacteriaceae

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) infection is an emerging clinical issue. One of the mechanisms of carbapenem-resistance is carbapenemase production. This study aimed to identify whether clinical outcomes differ by CRE resistance mechanism and to evaluate risk factors for mortality in patients with CRE bacteremia. Methods We conducted a retrospective cohort study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE and non-CP-CRE bacteremia during January 2011 to October 2018. Only monomicrobial Escherichia coli or Klebsiella pneumoniae bacteremia were included in the study. A modified carbapenem inactivation method was used for phenotypic detection of carbapenemase production. The presence of a variety of carbapenemase genes was evaluated by PCR with specific primers. Results Of 134 patients with monomicrobial CRE bacteremia, 48 (35.8%) were infected with CP-CRE, and 86 (64.1%) were infected with non-CP-CRE. The most common carbapenemase in CP-CRE isolates was KPC (66.7%), followed by NDM-1 (18.8%), OXA-48-like (10.4%), and VIM (4.1%). Baseline characteristics were similar between the two groups (Table 1). However, the CP-CRE group was significantly more likely to undergo removal of eradicable foci and to have meropenem MIC >8 µg/mL. A total of 33 (24.6%) patients died within 14 days, including 9 (18.8%) in the CP-CRE group and 24 (27.9%) in the non-CP-CRE group. Deceased patients were more likely to have a higher Pitt bacteremia score, nosocomial acquisition, ineradicable or not-eradicated foci, immunosuppressant use, inappropriate definitive treatment (Table 2). Combination therapy for definitive treatment was associated with decreased mortality. In a multivariate analysis including carbapenemase production, a higher Pitt bacteremia score (aOR, 5.15), ineradicable or not-eradicated foci (aOR, 4.05) and combination therapy for definitive treatment (aOR, 0.35) were independent risk factors for mortality. Conclusion Our study suggests that carbapenemase production is not a mortality risk factor in CRE bacteremia and provides additional evidence for early source control and combination therapy. Disclosures All authors: No reported disclosures.

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Participant Reactions to Suicide-Focused Research

Crisis ◽

10.1027/0227-5910/a000650 ◽

2020 ◽

Vol 41 (5) ◽

pp. 367-374

Author(s):

Sarah P. Carter ◽

Brooke A. Ammerman ◽

Heather M. Gebhardt ◽

Jonathan Buchholz ◽

Mark A. Reger

Keyword(s):

Medical Records ◽

Research Study ◽

Small Sample Size ◽

Psychiatric Inpatient ◽

Small Sample ◽

Inpatient Unit ◽

Online Laboratory ◽

Psychiatric Inpatient Unit ◽

Before And After ◽

Participant Reactions

Abstract. Background: Concerns exist regarding the perceived risks of conducting suicide-focused research among an acutely distressed population. Aims: The current study assessed changes in participant distress before and after participation in a suicide-focused research study conducted on a psychiatric inpatient unit. Method: Participants included 37 veterans who were receiving treatment on a psychiatric inpatient unit and completed a survey-based research study focused on suicide-related behaviors and experiences. Results: Participants reported no significant changes in self-reported distress. The majority of participants reported unchanged or decreased distress. Reviews of electronic medical records revealed no behavioral dysregulation and minimal use of as-needed medications or changes in mood following participation. Limitations: The study's small sample size and veteran population may limit generalizability. Conclusion: Findings add to research conducted across a variety of settings (i.e., outpatient, online, laboratory), indicating that participating in suicide-focused research is not significantly associated with increased distress or suicide risk.

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Disease Severity Is an Independent Risk Factor of Mortality and Outcomes in Critically Ill Patients With Carbapenem-resistant Klebsiella Pneumoniae Bloodstream Infections: a 5-year Retrospective Analysis

10.21203/rs.3.rs-658252/v1 ◽

2021 ◽

Author(s):

Yuzhen Qiu ◽

Wen Xu ◽

Yunqi Dai ◽

Ruoming Tan ◽

Jialin Liu ◽

...

Keyword(s):

Risk Factors ◽

Septic Shock ◽

Klebsiella Pneumoniae ◽

Critically Ill Patients ◽

Bloodstream Infections ◽

Polymyxin B ◽

Mortality Rates ◽

Carbapenem Resistant ◽

All Cause Mortality ◽

Independent Risk Factors

Abstract Background: Carbapenem-resistant Klebsiella pneumoniae bloodstream infections (CRKP-BSIs) are associated with high morbidity and mortality rates, especially in critically ill patients. Comprehensive mortality risk analyses and therapeutic assessment in real-world practice are beneficial to guide individual treatment.Methods: We retrospectively analyzed 87 patients with CRKP-BSIs (between July 2016 and June 2020) to identify the independent risk factors for 28-day all-cause mortality. The therapeutic efficacies of tigecycline-and polymyxin B-based therapies were analyzed.Results: The 28-day all-cause mortality and in-hospital mortality rates were 52.87% and 67.82%, respectively, arising predominantly from intra-abdominal (56.32%) and respiratory tract infections (21.84%). A multivariate analysis showed that 28-day all-cause mortality was independently associated with the patient’s APACHE II score (p = 0.002) and presence of septic shock at BSI onset (p = 0.006). All-cause mortality was not significantly different between patients receiving tigecycline- or polymyxin B-based therapy (55.81% vs. 53.85%, p = 0.873), and between subgroups mortality rates were also similar. Conclusions: Critical illness indicators (APACHE II scores and presence of septic shock at BSI onset) were independent risk factors for 28-day all-cause mortality. There was no significant difference between tigecycline- and polymyxin B-based therapy outcomes. Prompt and appropriate infection control should be implemented to prevent CRKP infections.

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O-225 Effects of SARS-Corona virus 2 on IVF treatment parameters: A cohort study of post COVID-19 patients

Human Reproduction ◽

10.1093/humrep/deab128.049 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Y Kabalkin ◽

M Gil ◽

E Lifshitz ◽

A Moav ◽

M Kabessa ◽

...

Keyword(s):

Cohort Study ◽

Virus Disease ◽

Small Sample Size ◽

Sperm Concentration ◽

Small Sample ◽

Cycle Performance ◽

Ang Ii ◽

P Values ◽

Corona Virus ◽

Before And After

Abstract Study question Does recovery from SARS–Corona virus 2 (SARS–CoV-2) infection negatively effect IVF cycle parameters? Summary answer Female IVF treatment parameters were comparable to the pre-Covid-19 infection cycle performance. Sperm concentration and motility demonstrated lower mean counts following Covid-19 infection. What is known already Corona-virus disease-19 (Covid-19) is a global pandemic caused by SARS–Corona virus 2 (SARS–CoV-2). The virus primarily affects the respiratory system, but other systemic and immune mediated effects have been reported. The spikes of SARS-CoV-2 have strong affinity for the Angiotensin converting enzyme (ACE) 2 receptor, leading to an increased Angiotensin II (Ang II) mediated pro-inflammatory response. ACE2 receptors exist in the human reproductive tract (more in males) and pose a regulatory role together with Ang II. So far, reports have been inconsistent regarding testicular effects. Other implications involving fertility and fertility treatment post infection are scarce. Study design, size, duration In this retrospective cohort study, IVF cycle performance was compared before and after Corona-virus disease-19. Patients were included only in cases where an IVF cycle was initiated within 3 months of Covid-19 recovery, between March 2020-December 2020. Participants/materials, setting, methods The study was conducted in a University affiliated IVF unit. Post Covid- 19 cycle parameters were compared to previous cycles of the same individual prior to infection. If previous cycles were not available, parameters were compared to non-exposed patients of same age, same treatment and identical indication. Sperm concentration and motility were compared before and after infection. Non exposure was defined by a lack of past Covid-19 diagnosis and a negative PCR throughout the treatment. Main results and the role of chance All together, including the matched cycles, we compared 40 cycles which started within 3 months of recovery: 26 fresh stimulation cycles and 14 frozen thawed transfer cycles. In 28 of these cycles the patient could serve as its own control. Mean age for the female partner was 33.2 years ±6.5 years. Eight male partners presented post infection and provided fresh samples for a cycle involving fertilization. We compared stimulation parameters including maximal Estradiol level, stimulation length, FSH dosage, number of oocytes retrieved, fertilization rates, number of embryos created, high quality embryo number and endometrial thickness. All of these were comparable to non-exposed cycles (generalized estimating equations, p values >0.1). No complications were recorded, specifically no thromboembolic events or respiratory complications. A total of 8 patients conceived: 1 was a chemical pregnancy, 1 extra-uterine pregnancy, 3 miscarriages and 3 ongoing, of those 1 was complicated by early bleeding. Male sperm analyses showed a trend towards lower post disease parameters, not reaching a statistical significance: 23mil/ml compared to 13.6 and 20.7% progressive motility compared to 12.3% (p values 0.09 and 0.17, respectively). Limitations, reasons for caution Current results are based on a small sample size, still insufficient for deducing definite conclusions or guidelines. Pregnancy outcome following IVF treatment in Covid-19 recoverees should further be studied. By the time of the conference, the number of cases is expected to be significantly higher. Wider implications of the findings This study provides preliminary data regarding the effects of SARS-COV-2 infection on IVF treatment outcomes. Despite the small sample size, treatment parameters seem unaffected, however, sperm performance seems to be compromised. Health policy and patients’ decisions regarding whether or not to postpone IVF procedures necessitates additional data. Trial registration number Not applicable - retrospective

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Approaches to multidrug-resistant organism prevention and control in long-term care facilities for older people: a systematic review and meta-analysis

Antimicrobial Resistance and Infection Control ◽

10.1186/s13756-021-01044-0 ◽

2022 ◽

Vol 11 (1) ◽

Author(s):

Valerie Wing Yu Wong ◽

Ying Huang ◽

Wan In Wei ◽

Samuel Yeung Shan Wong ◽

Kin On Kwok

Keyword(s):

Small Sample Size ◽

Meta Analysis ◽

Small Sample ◽

Risk Of Bias ◽

Source Control ◽

Resistant Organism ◽

Routine Practice ◽

Post Intervention ◽

Term Care ◽

Mrsa Colonization

Abstract Background Despite clear evidence of benefits in acute-care hospitals, controversy over the effectiveness of IPC measures for MDROs is perceptible and evidence-based practice has not been established. Objective To investigate the effects of IPC interventions on MDRO colonization and infections in LTCFs. Data sources Ovid MEDLINE, EMBASE, and CINAHL from inception to September 2020. Eligibility criteria Original and peer-reviewed articles examining the post-intervention effects on MDRO colonization and infections in LTCFs. Interventions (i) Horizontal interventions: administrative engagement, barrier precautions, education, environmental cleaning, hand hygiene, performance improvement, and source control; and (ii) vertical intervention: active surveillance plus decolonization. Study appraisal and synthesis We employed a random-effects meta-analysis to estimate the pooled risk ratios (pRRs) for methicillin-resistant Staphylococcus aureus (MRSA) colonization by intervention duration; and conducted subgroup analyses on different intervention components. Study quality was assessed using Cochrane risk of bias tools. Results Of 3877 studies identified, 19 were eligible for inclusion (eight randomized controlled trials (RCTs)). Studies reported outcomes associated with MRSA (15 studies), vancomycin-resistant Enterococci (VRE) (four studies), Clostridium difficile (two studies), and Gram-negative bacteria (GNB) (two studies). Eleven studies were included in the meta-analysis. The pRRs were close to unity regardless of intervention duration (long: RR 0.81 [95% CI 0.60–1.10]; medium: RR 0.81 [95% CI 0.25–2.68]; short: RR 0.95 [95% CI 0.53–1.69]). Vertical interventions in studies with a small sample size showed significant reductions in MRSA colonization while horizontal interventions did not. All studies involving active administrative engagement reported reductions. The risk of bias was high in all but two studies. Conclusions Our meta-analysis did not show any beneficial effects from IPC interventions on MRSA reductions in LTCFs. Our findings highlight that the effectiveness of interventions in these facilities is likely conditional on resource availability—particularly decolonization and barrier precautions, due to their potential adverse events and uncertain effectiveness. Hence, administrative engagement is crucial for all effective IPC programmes. LTCFs should consider a pragmatic approach to reinforce standard precautions as routine practice and implement barrier precautions and decolonization to outbreak responses only.

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A Pilot Placebo Controlled Randomized Trial of Dexamethasone for Chronic Subdural Hematoma

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2015.393 ◽

2016 ◽

Vol 43 (2) ◽

pp. 284-290 ◽

Cited By ~ 23

Author(s):

Michel Prud’homme ◽

François Mathieu ◽

Nicolas Marcotte ◽

Sylvine Cottin

Keyword(s):

Conservative Treatment ◽

Adverse Events ◽

Small Sample Size ◽

Chronic Subdural Hematoma ◽

Symptomatic Patient ◽

Placebo Treatment ◽

Small Sample ◽

Chi Square ◽

Serious Adverse Events ◽

Before And After

AbstractBackground: Current opinions regarding the use of dexamethasone in the treatment of chronic subdural hematomas (CSDH) are only based on observational studies. Moreover, the use of corticosteroids in asymptomatic or minimally symptomatic patient with this condition remains controversial. Here, we present data from a prospective randomized pilot study of CSDH patients treated with dexamethasone or placebo. Methods: Twenty patients with imaging-confirmed CSDH were recruited from a single center and randomized to receive dexamethasone (12 mg/day for 3 weeks followed by tapering) or placebo as a conservative treatment. Patients were followed for 6 months and the rate of success of conservative treatment with dexamethasone versus placebo was measured. Parameters such as hematoma thickness and clinical changes were also compared before and after treatment with chi-square tests. Adverse events and complications were documented. Results: During the 6-month follow-up, one of ten patients treated with corticosteroids had to undergo surgical drainage and three of ten patients were treated surgically after placebo treatment. At the end of the study, all remaining patients had complete radiological resolution. No significant differences were observed in terms of hematoma thickness profile and impression of change; however, patients experienced more severe side effects when treated with steroids as compared with placebo. Dexamethasone contributed to many serious adverse events. Conclusions: Given the small sample size, these preliminary results have not shown a clear beneficial effect of dexamethasone against placebo in our patients. However, the number of secondary effects reported was much greater for corticosteroids, and dexamethasone treatment was responsible for significant complications.

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Identifying the determinants of Malaysian corporate Sukuk rating

International Journal of Islamic and Middle Eastern Finance and Management ◽

10.1108/imefm-02-2017-0045 ◽

2018 ◽

Vol 11 (3) ◽

pp. 432-448 ◽

Cited By ~ 4

Author(s):

Nur Amirah Borhan ◽

Noryati Ahmad

Keyword(s):

Information Asymmetry ◽

Multinomial Logistic Regression ◽

Small Sample Size ◽

Small Sample ◽

Third Party ◽

Significant Variable ◽

Content Type ◽

Rating Agencies ◽

High Level ◽

Rating Category

Purpose This study aims to identify the determinants of Malaysian corporate Sukuk rating and attempts to find out which determinant has the most significant impact. Design/methodology/approach The framework tries to establish a relationship between firm’s size, profitability, Sukuk guarantee status and types of Sukuk with Sukuk rating from the perspective of Agency Theory and Information Asymmetry Theory. The data consist of 43 Sukuk issuances from 2006 to 2015. Multinomial Logistic Regression Model is then used to find out the significant determinants of Sukuk rating. Findings The study found that only three variables significantly impact Sukuk rating. The results show that a guaranteed Sukuk Ijarah or a guaranteed Sukuk Musyarakah that is issued by a highly profitable firm has a higher likelihood of getting rating AAA or rating AA as compared to getting rating A. A type of Sukuk, particularly Sukuk Murabahah, is the most significant variable influencing Sukuk rating. However, firm size is not a significant determinant of Sukuk rating in the context of this study. Research limitations implications The first limitation of the study is the relatively small sample size. Second, the study only tested four independent variables. Practical implications Several implications are derived from the results of the study. First, new firms that are planning to issue Sukuk should consistently maintain a high level of profit and consider issuing debt-based Sukuk to ensure that the issued Sukuk have higher rating. To increase the likelihood of getting higher rating, they should also consider providing a third-party guarantor. As for existing Sukuk issuers that are in lower rating category, they should increase their profitability to be upgraded to higher rating category. Second, risk-adverse investors should invest in highly profitable, guaranteed and debt-based Sukuk, as these Sukuk are likely to be in higher rating category and provide guarantee in terms of capital payments during liquidation or bankruptcy. Third, to reduce information asymmetry, policymakers should make it compulsory for all Sukuk issuers to have their Sukuk rated annually and make it mandatory for all rating agencies in Malaysia to publish their Sukuk rating methodologies. Originality/value This paper helps to expand the limited existing literature about the determinants of Sukuk rating, particularly for the Malaysian corporate Sukuk.

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Abstract 13215: Gender-affirming Hormones Are Associated With Increased Risk of QT Prolongation in Transgender Females

Circulation ◽

10.1161/circ.142.suppl_3.13215 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Daniel Antwi Amoabeng ◽

Ahmed Hanfy ◽

Munadel Awad ◽

Bryce D Beutler ◽

Amneet Rai ◽

...

Keyword(s):

Qt Interval ◽

Small Sample Size ◽

Qt Prolongation ◽

Small Sample ◽

Rank Test ◽

Qt Interval Prolongation ◽

Northern Nevada ◽

Increased Risk ◽

Before And After ◽

Signed Rank Test

Introduction: Women have a longer QT interval than men. This sex-specific difference is attributed to hormones associated with the biological female sex. Male-to-female transgender individuals often take antiandrogens such as spironolactone or goserelin in addition to estrogens to suppress testosterone effects while increasing feminine features. Effects of gender-affirming hormone therapy (GHT) on the QT interval in these individuals remains to be elucidated. Hypothesis: We assessed the hypothesis that the use of GHT is associated with an increased risk for QT interval prolongation in transgender females. Methods: We identified 46 transgender females through a search of the electronic medical records of a Veterans Administration hospital in Northern Nevada. Patients with a diagnosis of congenital long QT syndrome were excluded. Of these, 13 patients had ECGs before and after initiation of GHT and were included. We adapted the Tisdale score using the auto-calculated corrected QT interval (QTc) to estimate the risk of QT prolongation. Age, QTc, and Tisdale scores before and after GHT initiation were compared using the Wilcoxon signed-rank test. All tests were performed as two-tailed at a 5% level of significance. Results: All 13 study patients were taking estrogens. Of these, 3 (23.1%) were taking goserelin and 9 (69.2%) were taking spironolactone. Mean ± SEM age at ECG acquisition was 45.0 ± 4.4 and 47.7 ± 4.7 years before and after the initiation of GHT respectively. Mean ± SEM QTc after initiation of GHT was significantly higher compared to the baseline (467.5 ± 12.8 ms vs. 428.2 ± 7.1 ms) (Figure 1A). The average baseline Tisdale score was significantly smaller on follow-up (1-point vs. 3 points) (Figure 1B). Conclusions: GHT appears to be associated with increased QTc in transgender women. This needs to be interpreted with caution owing to the very small sample size in this study. Further studies to investigate the strength of this association, if it exists, are warranted.

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