A multi-species outbreak of VIM-producing carbapenem-resistant bacteria in a burn unit and subsequent investigation of rapid development of cefiderocol resistance.

Carbapenem resistance due to metallo-ß-lactamases (MBLs) such as the Verona integron-encoded metallo-ß-lactamase (VIM) is particularly problematic due to the limited treatment options. We describe a case series of bacterial infections in a tertiary care hospital due to multi-species acquisition of a VIM gene along with our experience using novel ß-lactam antibiotics and antibiotic combinations to treat these infections. Four patients were treated with the combination of ceftazidime-avibactam and aztreonam, with no resistance to the combination detected. However, cefiderocol-resistant Klebsiella pneumoniae isolates were detected in two out of the five patients who received cefiderocol within 3 weeks of having started the antibiotic. Strain pairs of sequential susceptible and resistant isolates from both patients were analyzed using whole-genome sequencing. This analysis revealed that the pairs of isolates independently acquired point mutations in both the cirA and fiu genes, which encode siderophore receptors. These point mutations were remade in a laboratory strain of K. pneumoniae and resulted in a significant increase in the MIC of cefiderocol, even in the absence of a beta-lactamase enzyme or a penicillin-binding protein 3 (PBP3) mutation. While newer ß-lactam antibiotics remain an exciting addition to the antibiotic armamentarium, their use must be accompanied by diligent monitoring for the rapid development of resistance.

Identifying barriers to compliance with a universal inpatient protocol for Staphylococcus aureus nasal decolonization with povidone-iodine.

Academic hospital nurses were surveyed to assess adherence barriers to a universal povidone-iodine nasal decolonization protocol to prevent Staphylococcus aureus infection. Low training rates, inadequate supplies, documentation and tracking challenges, patient refusal, and burnout contributed to suboptimal adherence. Prioritizing education is essential but alone is insufficient for successful protocol adoption.

Universal admission laboratory screening for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) asymptomatic infection across a large health system.

BACKGROUND: Admission laboratory screening for asymptomatic coronavirus disease 2019 (COVID-19) has been utilized to mitigate healthcare-associated severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission. An understanding of the impact of such testing across a variety of patient populations is needed. METHODS: SARS-CoV-2 nucleic acid amplification admission testing results for all asymptomatic patients across 4 distinct inpatient facilities between April 20, 2020, and June 14, 2021, were analyzed. Positivity rates and the number needed to test (NNT) to identify 1 asymptomatic infected patient were calculated. Admission results were compared to COVID-19 community incidence rates for the system's surrounding metropolitan service area. Using a national survey of hospital epidemiologists, a clinically meaningful NNT of 1:100 was identified. RESULTS: In total, 51,187 tests were collected (positivity rate, 1.8%). During periods of high transmission, the NNT met the clinically relevant threshold in all populations. The NNT approached or met the threshold for most locations during periods of lower transmission. For all transmission levels, the NNT for fully vaccinated patients did not meet the threshold. CONCLUSIONS: Implementing an asymptomatic patient admission testing program can provide clinically relevant data based on the NNT, even during periods of lower transmission and among different patient populations. Limiting admission testing to non-fully vaccinated patients during periods of lower transmission may be a strategy to address resource concerns around this practice. Although the impact of such testing on healthcare-associated COVID-19 among patients and healthcare workers could not be clearly determined, these data provide important information as facilities weigh the costs and benefits of such testing.

Hypercalcemia in pregnancy: a case of milk-alkali syndrome.

Milk-alkali syndrome is a rare cause of hypercalcemia characterized by the triad of hypercalcemia, renal insufficiency, and metabolic alkalosis that results from the overconsumption of calcium containing products. In the setting of pregnancy where there is a physiologic increase in calcium absorption, milk-alkali syndrome can be potentially life threatening. We report a case of a 26-year-old woman in her second trimester of pregnancy who presented with 2 weeks of flank pain, nausea, vomiting, anorexia, headache, and lightheadedness. The history revealed consumption of a large quantity of milk, calcium carbonate antacid, and calcium-containing prenatal vitamins. Her symptoms and hypercalcemia resolved with intravenous fluids and a loop diuretic. With the increased use of calcium carbonate for peptic ulcer disease, gastroesophageal reflux disease, and osteoporosis, milk-alkali syndrome has experienced a resurgence and must be considered in the differential diagnosis of hypercalcemia. In this clinical vignette we review the literature on milk-alkali syndrome in pregnancy and discuss important diagnostic and therapeutic considerations when managing the pregnant patient with hypercalcemia.

Assessing coronavirus disease 2019 (COVID-19) transmission to healthcare personnel: The global ACT-HCP case-control study.

OBJECTIVE: To characterize associations between exposures within and outside the medical workplace with healthcare personnel (HCP) SARS-CoV-2 infection, including the effect of various forms of respiratory protection. DESIGN: Case-control study. SETTING: We collected data from international participants via an online survey. PARTICIPANTS: In total, 1,130 HCP (244 cases with laboratory-confirmed COVID-19, and 886 controls healthy throughout the pandemic) from 67 countries not meeting prespecified exclusion (ie, healthy but not working, missing workplace exposure data, COVID symptoms without lab confirmation) were included in this study. METHODS: Respondents were queried regarding workplace exposures, respiratory protection, and extra-occupational activities. Odds ratios for HCP infection were calculated using multivariable logistic regression and sensitivity analyses controlling for confounders and known biases. RESULTS: HCP infection was associated with non-aerosol-generating contact with COVID-19 patients (adjusted OR, 1.4; 95% CI, 1.04-1.9; P = .03) and extra-occupational exposures including gatherings of ≥10 people, patronizing restaurants or bars, and public transportation (adjusted OR range, 3.1-16.2). Respirator use during aerosol-generating procedures (AGPs) was associated with lower odds of HCP infection (adjusted OR, 0.4; 95% CI, 0.2-0.8, P = .005), as was exposure to intensive care and dedicated COVID units, negative pressure rooms, and personal protective equipment (PPE) observers (adjusted OR range, 0.4-0.7). CONCLUSIONS: COVID-19 transmission to HCP was associated with medical exposures currently considered lower-risk and multiple extra-occupational exposures, and exposures associated with proper use of appropriate PPE were protective. Closer scrutiny of infection control measures surrounding healthcare activities and medical settings considered lower risk, and continued awareness of the risks of public congregation, may reduce the incidence of HCP infection.

Use of airborne infection isolation in potential cases of pulmonary tuberculosis.

OBJECTIVE: To identify risk factors of patients placed in airborne infection isolation (AII) for possible pulmonary tuberculosis (TB) to better predict TB diagnosis and allow more judicious use of AII. METHODS: Case-control, retrospective study at a single tertiary-care academic medical center. The study included all adult patients admitted from October 1, 2014, through October 31, 2017, who were placed in AII for possible pulmonary TB. Cases were defined as those ultimately diagnosed with pulmonary TB. Controls were defined as those not diagnosed with pulmonary TB. Those with TB diagnosed prior to admission were excluded. In total, 662 admissions (558 patients) were included. RESULTS: Overall, 15 cases of pulmonary TB were identified (2.7%); of these, 2 were people living with human immunodeficiency virus (HIV; PLWH). Statistical analysis was limited by low case number. Those diagnosed with pulmonary TB were more likely to have been born outside the United States (53% vs 13%; P < .001) and to have had prior positive TB testing, regardless of prior treatment (50% vs 19%; P = .015). A multivariate analysis using non-US birth and prior positive TB testing predicted an 18.2% probability of pulmonary TB diagnosis when present, compared with 1.0% if both factors were not present. CONCLUSIONS: The low number of pulmonary TB cases indicated AII overuse, especially in PLWH, and more judicious use of AII is warranted. High-risk groups, including those born outside the United States and those with prior positive TB testing, should be considered for AII in the appropriate clinical setting.

Scombroid Poisoning with Concurrent Brevundimonas Septicemia: A Unique Case Report and Brief Literature Review.

Scombroid poisoning is a predominantly self-limited illness associated with ingestion of poorly handled fish. It is not frequently associated with bacteremia and has never been described with Brevundimonas septicemia. We describe a case of a man who presented in shock with histamine poisoning after ingesting sushi. Blood cultures grew an uncommon pathogen, Brevundimonas vesicularis. This case demonstrates systemic bacterial infection in the setting of histamine poisoning, which is an atypical presentation for a well-known foodborne illness.

Ventilator Bundle Compliance and Risk of Ventilator-Associated Events.

OBJECTIVEVentilator bundles encompass practices that reduce the risk of ventilator complications, including ventilator-associated pneumonia. The impact of ventilator bundles on the risk of developing ventilator-associated events (VAEs) is unknown. We sought to determine whether decreased compliance to the ventilator bundle increases the risk for VAE development.DESIGNNested case-control study.SETTINGThis study was conducted at 6 adult intensive care units at an academic tertiary-care center in Tennessee.PATIENTSIn total, 273 patients with VAEs were randomly matched in a 1:4 ratio to controls by mechanical ventilation duration and ICU type.METHODSControls were selected from the primary study population at risk for a VAE after being mechanically ventilated for the same number of days as a specified case. Using conditional logistic regression analysis, overall cumulative compliance, and compliance with individual components of the bundle in the 3 and 7 days prior to VAE development (or the control match day) were examined.RESULTSOverall bundle compliance at 3 days (odds ratio [OR], 1.15; P=.34) and 7 days prior to VAE diagnosis (OR, 0.96; P=.83) were not associated with VAE development. This finding did not change when limiting the outcome to infection-related ventilator-associated complications (IVACs) and after adjusting for age and gender. In the examination of compliance with specific bundle components increased compliance with chlorhexidine oral care was associated with increased risk of VAE development in all analyses.CONCLUSIONSVentilator bundle compliance was not associated with a reduced risk for VAEs. Higher compliance with chlorhexidine oral care was associated with a greater risk for VAE development.Infect Control Hosp Epidemiol 2018;39:637-643.

Reducing Inappropriate Testing for the Evaluation of Diarrhea Among Hospitalized Patients.

BACKGROUND: Diarrhea is one of the most common illnesses in the United States. Evaluation frequently does not follow established guidelines. The objective of this study was to evaluate the effectiveness of a computerized physician order entry-based test guidance algorithm with regard to the clinical, financial, and operational impacts. METHODS: Our population was patients with diarrheal illness at a tertiary academic medical center. The intervention was a computerized physician order entry-based test guidance algorithm that restricted the use of stool cultures and ova and parasites testing of diarrhea in the adult inpatient location vs nonintervention sites, which were the emergency department, pediatric inpatient and adult and pediatric outpatient locations. We measured stool culture, ova and parasites, and Clostridium difficile testing rates from July 1, 2012 to January 31, 2016. Additionally, we calculated advisor usage, consults generated, accuracy of information, and cost savings. RESULTS: There was a significant decrease in stool culture and ova and parasites testing rates at the adult inpatient (P = .001 for both), pediatric (P < .001 for both), and adult emergency department (P < .001; P = .009) locations. The decrease at the intervention site was immediate, whereas the other locations showed a delayed but sustained decrease that suggests a collateral impact. A significant increase in the rate of stool culture and ova and parasites testing was observed in the outpatient setting (P = .02 and P = .001). We estimate that $21,931 was saved annually. CONCLUSIONS: A point-of-order test restriction algorithm for hospitalized adults with diarrhea reduced stool testing. Similar programs should be considered at other institutions and for the evaluation of other conditions.

Risk Factors and Outcomes Associated With Acquisition of Daptomycin and Linezolid-Nonsusceptible Vancomycin-Resistant Enterococcus.

BACKGROUND: Vancomycin-resistant enterococcus (VRE) causes substantial health care-associated infection with increasing reports of resistance to daptomycin or linezolid. We conducted a case-control study reporting 81 cases of daptomycin and linezolid-nonsusceptible VRE (DLVRE), a resistance pattern not previously reported. METHODS: We reviewed VRE isolates from June 2010 through June 2015 for nonsusceptibility to both daptomycin (minimum inhibitory concentration [MIC] > 4) and linezolid (MIC ≥ 4). We matched cases by year to control patients with VRE susceptible to both daptomycin and linezolid and performed retrospective chart review to gather risk factor and outcome data. RESULTS: We identified 81 DLVRE cases. Resistance to both daptomycin and linezolid was more common than resistance to either agent individually. Compared with susceptible VRE, DLVRE was more likely to present as bacteremia without focus (P < 0.01), with DLVRE patients more likely to be immune suppressed (P = .04), to be neutropenic (P = .03), or to have had an invasive procedure in the prior 30 days (P = .04). Any antibiotic exposure over the prior 30 days conferred a 4-fold increased risk for DLVRE (odds ratio [OR], 4.25; 95% confidence interval [CI], 1.43-12.63; P = .01); multivariate analysis implicated daptomycin days of therapy (DOT) over the past year as a specific risk factor (OR, 1.10; 95% CI, 1.01-1.19; P = .03). DLVRE cases had longer hospitalizations (P = .04) but no increased risk for in-hospital death. CONCLUSIONS: DLVRE is an emerging multidrug-resistant pathogen associated with immune suppression, neutropenia, and recent invasive procedure. Prior antibiotic exposure, specifically daptomycin exposure, confers risk for acquisition of DLVRE.

GH1 splicing is regulated by multiple enhancers whose mutation produces a dominant-negative GH isoform that can be degraded by allele-specific small interfering RNA (siRNA).

The majority of mutations that cause isolated GH deficiency type II affect splicing of GH1 transcripts, leading to the production of a dominant-negative GH isoform. Because numerous mutations and polymorphisms throughout the GH1 gene have not yet been tested for aberrant splicing, we used a deletion mutagenesis screen across intron 2-exon 3-intron 3 to identify splicing regulatory sequences. These analyses identified a new enhancer element, ESE2, upstream of the cryptic splice site in exon 3 and further defined a previously described enhancer (ESE1) to include the first seven nucleotides of exon 3. Besides enhancers, the overall size of intron 3 is also crucial for exon inclusion. Given the deleterious effects of the dominant-negative 17.5-kDa isoform, these and previous studies underscore the extent to which splicing regulatory elements serve to prevent exon skipping. Importantly, we show here that small interfering RNAs can be used to specifically degrade exon 3-skipped transcripts, potentially a new avenue of therapeutic intervention in isolated GH deficiency II and other dominant disorders.