Delay In Appropriate Therapy Research Articles

Adult Vitamin B12 Deficiency-Associated Pseudo-Thrombotic Microangiopathy: A Systematic Review of Case Reports.

Cobalamin-deficient thrombotic microangiopathy or vitamin B12 deficiency presenting as pseudo-thrombotic microangiopathy is a rare disorder that can be misdiagnosed as thrombotic thrombocytopenic purpura. Patients with this condition are at risk of receiving unnecessary plasmapheresis with a potential delay in appropriate therapy with vitamin B12 supplementation. There are no established diagnostic criteria for this condition in clinical practice. We performed a systematic review of case reports published between January 2018 and January 2023 to analyze the clinical characteristics, risk factors, and patterns of laboratory markers to improve the diagnostic criteria for this condition.

Emergent rescue transjugular intrahepatic portosystemic shunt within 8h improves survival in patients with refractory variceal bleed.

Transjugular-intrahepatic portosystemic-shunt (TIPS) and SX-Ella stentDanis (DE stent) are available rescue therapies for refractory variceal bleeding in cirrhosis. Any delay in appropriate therapy is associated with high mortality. Determining the best timing for rescue TIPS is crucial and largely unknown. Cirrhotic patients with refractory variceal bleed (n = 121) who underwent rescue TIPS within 24-h (n = 66) were included. Their early rebleed (upto 42days) rate, 6-week and 1-year survival were compared with matched patients who underwent rescue DE stent (n = 55). Outcomes based on timing of TIPS (within 8-h/8-24h) were also analyzed. At baseline, patients who received rescue DE stent were sicker with higher MELD score (27.6 ± 8.3 vs. 22.3 ± 7.9; p = 0.001), active bleeding at endoscopy (54.5% vs. 34.8%; p = 0.03) compared to TIPS-group. After propensity score matching, adjusting for MELD-Na score and non-bleed complications, DE patients (n = 34) had higher mortality at 6-week (17/34; 50%) and 1-year (29/34; 85.3%) compared to TIPS-group (20.6% and 38.2%, respectively; both p < 0.02), with higher rebleeding rate (10/34; 29.4% vs. 1/34; 2.9%, p = 0.003). Rescue TIPS placed within 8-h compared with 8-24h had lower 6-week (48.6% vs. 12.9%; p = 0.003) and 1-year mortality (62.9% vs. 16.1%, p = 0.001) despite comparable rebleed rates (2/31; 6.5% vs. 2/35;5.7%; p = 0.90). Post-TIPS Portal pressure gradientat6-weeksand1-year was comparable betweensurvivorsandnon-survivors. Active bleeding at endoscopy [HR = 11.8; 95% CI2.96-47.53], presence of AKI [HR = 5.8; 95% CI 1.92-17.41], MELD-Na > 24 [HR = 1.1; 95% CI 1.0-1.17], mean arterial pressure > 64.5mmHg [HR = 0.8; 95% CI 0.75-0.92] independently predicted 6-week mortality in rescue TIPS-group. Rescue TIPS placement preferably within 8-h of refractory variceal bleed improves short- and long-term survival. It provides better outcome than DE stent for control of bleeding and prevention of rebleeding, even in patients with high MELD-Na score.

Should patients with Parkinson’s disease only visit a neurologist’s office? - a narrative review of neuropsychiatric disorders among people with Parkinson’s disease

Abstract Introduction: Parkinson’s disease is a neurodegenerative disease that is often accompanied by disorders such as depression, psychotic disorders, cognitive disorders, anxiety disorders, sleep disorders, impulse control disorders. The aim of the study was to review the literature and present the characteristics of neuropsychiatric disorders occurring in people suffering from Parkinson’s disease, with the specification of the above-mentioned disorders. Material and method: The literature available on the PubMed platform from 1986 to 2022 was reviewed using the following keywords: Parkinson’s disease, depression, anxiety disorders, psychotic disorders, sleep disorders, cognitive disorders, impulse control disorders. Original studies, reviews, meta-analyzes and internet sources were analyzed. Results: The above-mentioned neuropsychiatric disorders appear with different frequency among people suffering from Parkinson’s disease and occur at different times of its duration or even precede its onset for many years. The non-motor symptoms in the form of depressed mood, energy loss or changes in the rhythm of the day may result in a delay of appropriate therapy and thus in complications. Neuropathological changes in the course of Parkinson’s disease as well as dopaminergic drugs used in its therapy influence the development of neuropsychiatric disorders. Conclusions: In order to avoid misdiagnosis, practitioners should use, e.g. scales intended for patients with Parkinson’s disease. To prevent the consequences of the aforementioned disease entities, methods of early diagnosis, determination of risk factors and standardization of the treatment process must be determined. Consistent care for patients with Parkinson’s disease is significant, not only in the neurological field, but also in the psychiatric one.

Incidence and risk factors of urinary tract infection in neonatal sepsis

BackgroundNeonates with sepsis may have concurrent urinary tract infection (UTI), which may be asymptomatic or have nonspecific symptoms. Failure to diagnose UTI, resulting in a delay of appropriate therapy, has been reported to cause renal scarring, hypertension, and kidney failure among infants. This study aimed to determine the contribution of UTI to neonatal sepsis and to assess different risk factors that could be associated with UTI. This cross-sectional study was conducted at the Neonatal Intensive Care Unit (NICU) of Fayoum University Hospital, Fayoum, Egypt, between March 2018 and January 2019. Neonates of both genders from birth to the 28th day of life with clinical features of either early- or late-onset sepsis (during or after the first 3 days of life, respectively) were enrolled in this study. All neonates were subjected to complete history taking from the parents, full clinical examination, and laboratory investigations including complete blood count, C-reactive protein, blood culture, and urine culture.ResultsThe current study included 100 neonates admitted to the NICU with clinical and laboratory features of sepsis. Positive blood culture (proven sepsis) was detected in 60%, and the proportion of positive urine culture (UTI) in the entire study group was 11%. The incidence of UTI was 11.7% in proven sepsis compared to 10% in suspected sepsis, and it was 16.36% in late-onset sepsis (LOS) versus 4.44% in early-onset sepsis (EOS). There was a statistically significant association between poor feeding and feeding intolerance and positive urine culture (UTI). Leukopenia and expert panel criteria score showed high sensitivity (81.80% and 90.90%, respectively) but low specificity for the diagnosis of UTI.ConclusionsGram-negative bacteria have been highly suspected in cases of neonatal sepsis. Poor feeding and feeding intolerance have association with positive urine culture. Finally, urine culture for sepsis was recommended especially in the late type.

Inappropriate antibiotic administration in the setting of Charcot arthropathy: A case series and literature review

AimsDifferentiating Charcot neuropathic osteoarthropathy (CN) from infection is challenging. The diagnosis of CN is often missed or delayed, resulting in inappropriate and delayed treatment. We hypothesized that the misdiagnosis of CN results in inappropriate antibiotic prescriptions and explore the sequelae of unnecessary antibiotic use. MethodsA retrospective review of patient electronic medical records from January 2010 to December 2017 was conducted for those diagnosed with CN after being referred to an orthopaedic foot and ankle specialist. ResultsOur review showed 58 of 103 (56%) patients received antibiotics on the date, or within the next 7 days, of referral to foot and ankle orthopaedic specialist. The antibiotic of choice given on referral were as follows: Sulfamethoxazole/Trimethoprim 18 of 58 (31%), doxycycline 13 of 58 (22%), clindamycin 13 of 58 (22%), cephalexin 9 of 58 (16%), minocycline 5 of 58 (9%). ConclusionMissed diagnoses for CN are common and result in complications stemming from inappropriate treatment, delays in appropriate therapy, and may accelerate antibiotic resistance. Misdiagnosis of CN contributes to the inappropriate use of prescription antibiotics.

Impact of Incremental Delays in Appropriate Therapy on the Outcomes of Hospitalized Adult Patients with Gram-negative Bloodstream Infections: "Every day matters".

Serious bloodstream infections (BSIs) are often caused by Gram-negative (GN) bacteria in hospitalized patients. Treatment of these infections has been further complicated by the continued rise and spread of drug-resistant pathogens, including carbapenem resistant (CR) strains of Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa. This retrospective cohort analysis used real-world data from a large United States hospital-based database to examine the association between key clinical outcomes and different lengths of time to appropriate treatment between October 2010 and September 2015. Of 40,549 patients with GN-BSIs who were identified, 1117 (2.8%) had a CR GN-BSI. Overall, outcomes of hospitalized adult patients with GN-BSIs incrementally worsened the longer appropriate therapy was delayed. Patients with CR GN-BSIs had a median infection-associated length of stay (LOS) of 8, 9, 10, and 13days, whereas patients with CS GN-BSIs had a median infection-associated LOS of 6, 7, 8, and 11days for patients with days to appropriate therapy of 0, 1-2, 3-4, and ≥5days, respectively. Among patients with CR GN-BSIs, the percentage of patients discharged home was 38%, 33%, 35%, and 31%, whereas in patients with CS GN-BSIs, the percentage of patients discharged home was 58%, 53%, 48%, and 43% for patients with days to appropriate therapy of 0, 1-2, 3-4, and ≥5days, respectively. The findings from this study highlight the clear need to deliver appropriate therapy more expeditiously in patients with CS and CR GN-BSIs.

SUN-492 Treatment of Uncontrolled Graves’ Disease Reveals Underlying Thyroiditis

Thyrotoxicosis is a life-threatening condition that may result from poor adherence to medical therapy. We describe the case of a patient with Graves’ disease and a history of medication non-compliance who presented with tachyarrhythmia and heart failure (HF). His protracted course after weeks of inpatient treatment with thionamides, iodine, resin and beta-blockers, was followed by a dramatic improvement within days of adding steroids, suggesting the presence of concurrent untreated thyroiditis. Case Description: A 38-year-old man with an 18-month history of known Graves’ disease presented to the endocrinology clinic requesting thyroidectomy. He complained of 3 weeks of worsening palpitations, shortness of breath, bilateral lower extremity edema, and frequent loose stools. History revealed frequent interruption of thionamide and recent discontinuation of propranolol due to patient’s perceived lack of improvement. Physical exam showed a thin male with a large goiter. He was in moderate distress due to tachypnea. He had atrial fibrillation with rapid ventricular rate (A Fib with RVR) but was not in pulmonary edema. Laboratories showed a suppressed TSH (<0.02 mIU/L [0.45 - 4.70 mIU/L]), a free T4 above the level of detection (>6.99 ng/dL [0.78 - 2.20 ng/dL], and a total T3 level of above 781 pg/mL (97.0 - 170.0 ng/dL). Methimazole 30 mg BID and propranolol 40 mg TID were started, followed within a few hours with potassium iodine (SSKI) 3 drops TID. Although the patient’s HF improved and there was down-trending of free T4, he continued to have A fib with RVR. SSKI and propranolol were increased; diltiazem 90 mg QID and cholestyramine 2g BID were later added. Despite aggressive treatment, the patient continued to have intermittent tachyarrhythmia, postponing his planned thyroidectomy for weeks. Dexamethasone 2mg Q8H was then started aiming to further decrease T4 to T3 conversion. Interestingly, within 48 hours of the start of steroid therapy, his free T4 level markedly decreased and was well within the normal range several days later when he underwent a successful thyroidectomy, with no further tachyarrhythmia recurrence. Discussion: Thyrotoxicosis is aggressively treated given its high mortality rate. Treatment algorithms guide physicians to categorize hyperthyroidism either as the type associated with increased hormone synthesis and secretion or that which results from increased hormone release due to gland destruction. This thought process may lead, as in our case, to a delay in appropriate therapy and an increased risk of disease complications. Furthermore, providers should not assume that the lack of treatment response in a patient with Graves’ disease is the result of medication non-adherence. The possibility of coexisting thyroiditis and the absence of a treatment regimen that effectively addresses both underlying processes may be the actual cause for the lack of clinical improvement.

2009. Evaluation of Time to Organism Identification and Pharmacist Impact on Antibiotic Prescribing through Utilization of MALDI-TOF at Two Community, Teaching Hospitals

BackgroundIn patients with bacteremia, delay in appropriate therapy is associated with higher morbidity and mortality. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) reduces the time to identification (ID) to approximately 30 minutes. Previously published studies show rapid diagnostics need to be coupled with antibiotic stewardship intervention for maximal benefit.MethodsRetrospective, observational review at Cambridge and Everett Hospitals, two inpatient community, teaching hospitals that are part of Cambridge Health Alliance. The purpose is to evaluate the impact of MALDI-TOF by reviewing data in three phases: Microscan ID (January 1 to November 30, 2017), MALDI-TOF alone (December 1, 2017 to December 9, 2018), and MALDI-TOF coupled antimicrobial stewardship (December 10, 2018 to April 30, 2019). The laboratory batches all positive blood cultures to be run via MALDI-TOF mid-morning. In phase 3, a pharmacy resident is notified of the result via an automatic page. The resident determines appropriate empiric therapy using an algorithm developed by the Antimicrobial Stewardship Team and contacts the primary team. Data were collected via a laboratory report and chart review. The primary outcome is time to targeted antimicrobial therapy after ID. Secondary outcomes include time to ID, time to susceptibilities, duration of therapy for blood culture contaminants, and number of pharmacy interventions in phase 3.ResultsPreliminary data indicate mean time targeted antibiotic therapy was 41:45, 35:58, and 27:39 hours:minutes in phases 1, 2, and 3, respectively. Mean time to ID and final susceptibilities was also reduced in phases 2 and 3. The duration of therapy for blood culture contaminants decreased from 53:50 in phase 1 to 32:48 hours:minutes in phase 2. Pharmacy residents in phase 3 successfully implemented 47 total interventions, 24 (51%) after identification.ConclusionImplementation of MALDI-TOF with and without stewardship intervention successfully decreased time to targeted antibiotic therapy in two community hospitals. Future directions include adding an evening MALDI-TOF run and simplifying pharmacy resident standard operating procedure.Disclosures All authors: No reported disclosures.

216. Association Between Days to Initiate Appropriate Therapy and Hospital Length of Stay Among Adult Hospitalized Patients With Gram-negative Bloodstream Infections (GN-BSI)

BackgroundThe deleterious outcomes associated with delay receipt of appropriate therapy are well documented. However, scant data exists on the consequences of each day delay of appropriate therapy and subsequent outcomes among adult hospitalized patients with GN-BSIs.MethodsStudy design: a retrospective cohort analysis. Study population: consecutive adult, hospitalized patients with a GN-BSI (11 most prevalent pathogens) in 1 of 181 institutions contributing microbiology data to the Premier Healthcare Database (October 2010–Sep 2015). Exclusion criteria: age < 18 years; diagnosis of pregnancy or cystic fibrosis, died or discharged within 2 days of index GN-BSI culture, lack of sufficient antibiotic susceptibility or treatment data to determine appropriateness. Day of initiating appropriate therapy was defined as the first day when the patient received an antibiotic with in vitro activity against the GN-BSI post index culture. Results were summarized by Kaplan–Meier estimates, and Cox Proportional-Hazards (CPH) analyses modeling discharge to home were conducted. Time to initiate appropriate therapy (0, 1–2 days, 3–4 days, ≥5 days) was included in the CPH model as an ordinal variable.ResultsA total of 40,549 patients met selection criteria. Mean (SD) age was 67.5 (16.1) years and 54% were female. E. coli and K. pneumoniae were the most common GN-BSI (58.0% and 18.3%, respectively). Approximately 30% of patients were in the ICU at index GN-BSI and in-hospital mortality was 6.8%. The mean (SD) time to receive appropriate therapy post index GN-BSI culture was 0.6 (2.7) days, and 69.7%, 22.5%, 5.7% and 2.1% received appropriate therapy in 0, 1–2, 3–4, and ≥5 days of index GN-BSI, respectively. The mean/median LOS post index GN-BSI by 0, 1–2, 3–4, and ≥5 days delays in appropriate treatment were 8.3/6, 9.8/7, 11.5/8, and 19.2/11 days respectively. Kaplan–Meier plots are shown in Figure 1. In the CPH model, each interval delay in appropriate therapy was associated with a 21% decrease in the likelihood of being discharged home for patients with GB-BSIs.ConclusionHospital length of stay was found to increase when appropriate therapy was delayed. These findings highlight the critical need for early appropriate therapy among patients with GN-BSIs. Disclosures All authors: No reported disclosures.

Impact of appropriateness of empiric therapy on outcomes in community-onset bacteremia by extended-spectrum-β-lactamase producing Escherichia coli and Klebisella pneumoniae definitively treated with carbapenems.

Despite a significant increase of bloodstream infection caused by extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae in the community-setting, information regarding clinical outcomes of inappropriate empiric therapy (IAT) in patients with those infections is limited. A multicenter-retrospective cohort study was conducted in four hospitals. A total of 249 adults were identified to have community-onset bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae, and definitively treated with carbapenems. According to the appropriateness of empiric therapy, individuals were divided into an appropriate empiric therapy (AT) group (n=106) and IAT group (n=143). Patients who received AT showed more severe underlying conditions including underlying solid cancer, healthcare-association and intensive care unit (ICU) care, compared to the IAT group. Primary bacteremia was more commonly found in the AT group than in the IAT group, while urinary tract infection predominated more frequently in the IAT group than in the AT group. Multivariate analysis using propensity score analysis indicated that inappropriateness of empiric therapy was not an independent risk factor for 30-day death. ICU care, respiratory tract infection and underlying liver, renal and connective tissue diseases were significantly associated with mortality. In patients with bloodstream infections caused by ESBL-producing E. coli and K. pneumoniae in the community-setting, delay in appropriate therapy was not associated with an increased rate of death if the patients were definitively treated with carbapenems.

Timing to antibiotic therapy in septic oncologic patients presenting without hypotension.

Sepsis accounts for only 2% of the hospitalizations worldwide but more than 17% of total in-hospital mortality. Inappropriate antimicrobial selection and delays in appropriate therapy have been associated with reduced survival in severe sepsis and septic shock. No studies to date have exclusively targeted septic oncologic patients without hypotension. This study was a retrospective chart review of 100 adult cancer patients presenting to the emergency department with sepsis without hypotension. We investigated the effect of time to appropriate antibiotics on in-hospital mortality and hospital length of stay. It was hypothesized that increased time to antibiotic administration would worsen patient outcomes including in-hospital mortality and length of stay. Each 1-h delay in administration of appropriate antibiotic therapy increased the odds of in-hospital mortality by 16% (adjusted OR 1.16. 95% CI 1.04-1.34, p=0.04). Time to appropriate antibiotics had no effect on hospital length of stay. Time to appropriate antibiotics and in-hospital mortality were associated in this population of adult oncologic patients with sepsis without hypotension. Clinicians in the emergency department should strive to ensure the timely administration of a complete and appropriate empiric antibiotic regimen in septic patients with active cancer even in the absence of hypotension.

A simple scoring algorithm predicting extended-spectrum β-lactamase producers in adults with community-onset monomicrobial Enterobacteriaceae bacteremia: Matters of frequent emergency department users.

The incidence of community-onset bacteremia caused by extended-spectrum-β-lactamase (ESBL) producers is increasing. The adverse effects of ESBL production on patient outcome have been recognized and this antimicrobial resistance has significant implications in the delay of appropriate therapy. However, a simple scoring algorithm that can easily, inexpensively, and accurately be applied to clinical settings was lacking. Thus, we established a predictive scoring algorithm for identifying patients at the risk of ESBL-producer infections among patients with community-onset monomicrobial Enterobacteriaceae bacteremia (CoMEB).In a retrospective cohort, multicenter study, adults with CoMEB in the emergency department (ED) were recruited during January 2008 to December 2013. ESBL producers were determined based on ESBL phenotype. Clinical information was obtained from chart records.Of the total 1141 adults with CoMEB, 65 (5.7%) caused by ESBL producers were identified. Four independent multivariate predictors of ESBL-producer bacteremia with high odds ratios (ORs)—recent antimicrobial use (OR, 15.29), recent invasive procedures (OR, 12.33), nursing home residents (OR, 27.77), and frequent ED user (OR, 9.98)—were each assigned +1 point to obtain the CoMEB-ESBL score. Using the proposed scoring algorithm, a cut-off value of +2 yielded a high sensitivity (84.6%) and an acceptable specificity (92.5%); the area under the receiver operating characteristic curve was 0.92.In conclusion, this simple scoring algorithm can be used to identify CoMEB patients with a high ESBL-producer infection risk. Of note, frequent ED user was firstly demonstrated to be a crucial predictor in predicting ESBL-producer infections. ED clinicians should consider adequate empirical therapy with coverage of these pathogens for patients with risk factors.

Carbapenem-resistant Klebsiella pneumoniae in high-risk haematological patients: factors favouring spread, risk factors and outcome of carbapenem-resistant Klebsiella pneumoniae bacteremias

BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) spread and infections in patients with haematological malignancies are a serious concern especially in endemic areas. Treatment failures and delay in appropriate therapy for CRKP infections are frequent and the mortality rate associated with CRKP bacteremia in neutropenic haematological patients is reported about 60%.MethodsHaematological patients harboring CRKP hospitalized between February 2012 and May 2013 in an Italian Teaching hospital were examined. Conditions favouring CRKP spread in a haematological unit, risk factors for bacteremia in CRKP-carriers and for CRKP bacteremia-related death were evaluated in this observational retrospective study.ResultsCRKP was isolated in 22 patients, 14 (64%) had bacteremia. Control measures implementation, particularly the weekly rectal screening for CRKP performed in all hospitalized patients and contact precautions for CRKP-carriers and newly admitted patients until proved CRKP-negative, reduced significantly the CRKP spread (14 new carriers identified of 131 screened patients vs 5 of 242 after the intervention, p = 0.001). Fifty-eight percent of carriers developed CRKP bacteremia, and acute myeloid leukemia (AML) resulted independently associated with the bacteremia occurrence (p = 0.02). CRKP bacteremias developed mainly during neutropenia (86%) and in CRKP-carriers (79%). CRKP bacteremias were breakthrough in 10 cases (71%). Ten of 14 patient with CRKP bacteremias died (71%) and all had AML. The 70% of fatal bacteremias occurred in patients not yet recognized as CRKP-carriers and 80% were breakthrough. Initial adequate antibiotic therapy resulted the only independent factor able to protect against death (p = 0.02).ConclusionsThe identification of CRKP-carriers is confirmed critical to prevent CRKP spread. AML patients colonized by CRKP resulted at high risk of CRKP-bacteremia and poor outcome and the adequacy of the initial antibiotic therapy may be effective to improve survival. To limit the increase of resistance, the extensive use of antibiotics active against CRKP should be avoided, but in the setting of high CRKP pressure and high-risk CRKP-colonized haematological patients, timely empiric antibiotic combinations active against CRKP could be suggested as treatment of febrile neutropenia.

Clinical and microbiologic characteristics of cefotaxime-non-susceptible Enterobacteriaceae bacteremia: a case control study

BackgroundCefotaxime plays an important role in the treatment of patients with bacteremia due to Enterobacteriaceae, although cefotaxime resistance is reported to be increasing in association with extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase (AmpC).MethodsWe conducted a case-control study in a Japanese university hospital between 2011 and 2012. We assessed the risk factors and clinical outcomes of bacteremia due to cefotaxime-non-susceptible Enterobacteriaceae (CTXNS-En) and analyzed the resistance mechanisms.ResultsOf 316 patients with Enterobacteriaceae bacteremia, 37 patients with bacteremia caused by CTXNS-En were matched to 74 patients who had bacteremia caused by cefotaxime-susceptible Enterobacteriaceae (CTXS-En). The most common CTXNS-En was Escherichia coli (43%), followed by Enterobacter spp. (24%) and Klebsiella spp. (22%). Independent risk factors for CTXNS-En bacteremia included previous infection or colonization of CTXNS-En, cardiac disease, the presence of intravascular catheter and prior surgery within 30 days. Patients with CTXNS-En bacteremia were less likely to receive appropriate empirical therapy and to achieve a complete response at 72 h than patients with CTXS-En bacteremia. Mortality was comparable between CTXNS-En and CTXS-En patients (5 vs. 3%). CTXNS-En isolates exhibited multidrug resistance but remained highly susceptible to amikacin and meropenem. CTX-M-type ESBLs accounted for 76% of the β-lactamase genes responsible for CTXNS E. coli and Klebsiella spp. isolates, followed by plasmid-mediated AmpC (12%). Chromosomal AmpC was responsible for 89% of CTXNS Enterobacter spp. isolates.ConclusionsCTXNS-En isolates harboring ESBL and AmpC caused delays in appropriate therapy among bacteremic patients. Risk factors and antibiograms may improve the selection of appropriate therapy for CTXNS-En bacteremia. Prevalent mechanisms of resistance in CTXNS-En were ESBL and chromosomal AmpC.

Evaluation of a Multiplex PCR Assay with Molecular Beacon Probes to Rapidly Detect Bacterial Pathogens Directly in Bronchial Alveolar Lavage (BAL) Samples from Patients with Hospital-Acquired Pneumonia (HAP)

BackgroundBacterial pneumonia is a common complication in hospitalized patients and it is associated with high morbidity and mortality. Standard culture-based methods may take 2–3 days to identify the etiologies of HAP, leading to delays in appropriate therapy. A rapid molecular assay that could diagnose the etiology of bacterial pneumonia directly from BAL samples within a few hours could facilitate faster and more directed administration of antimicrobial therapy.MethodsBAL samples were collected from hospitalized patients with suspected pneumonia, including ventilated patients, from December 2016 through April 2017. Genomic DNA was isolated from BAL samples using NucliSENS® easyMAG®. A panel of target-specific molecular beacon probes in a real time PCR assay (MB-PCR) was used to identify the following pathogens: universal bacterial Identification (16S rRNA), E. coli (uidA), K. pneumoniae (gapA), S. aureus (spa), P. aeruginosa (rpsL), A. baumannii (Ab-ITS) and the following resistance determinants: ESBLs (CTX-M, TEM and SHV), carbapenemases (NDM, VIM, IMP, OXA-48 and KPC) and mecA. The results of MB-PCR were then compared with quantitative culture results performed by the clinical microbiological lab.ResultsWe evaluated 53 BAL samples to identify the bacterial pathogen and key resistance determinants. Thirty-one samples yielded growth of ≥1 × 104 CFU/mL of bacteria by quantitative culture. The bacterial identification using MB-PCR for 16S rRNA correctly identified the presence of bacteria in all 31 samples (100% sensitivity). The MB-PCR identified P. aeruginosa (n = 5), S. aureus (n = 5), E. coli (n = 1), A. baumannii (n = 1), and K. pneumoniae (n = 1) in BAL samples that yielded ≥1 × 104 CFU/mL of the same pathogen by culture (100% sensitivity). The MB-PCR also identified blaTEM-harboring E. coli that grew ampicillin-resistant E. coli by culture. The specificity of the16S rRNA probe was 70%, as 7/53 BAL were false positive, whereas the specificity for the MB-PCR was 100% for P. aeruginosa, S. aureus, E. coli, and A. baumannii, and 98% for K. pneumoniae.ConclusionMultiplex MB-PCR assay is a rapid, sensitive and specific tool for detection of common bacterial causes of nosocomial pneumonia and important resistance determinants directly from BAL samples.Disclosures M. Satlin, Hardy Diagnostics: Investigator, Research support; S. G. Jenkins, Cormedix: Consultant, Consulting fee; Bayer: Consultant, Consulting fee Merck: Grant Investigator and Scientific Advisor, Research grant; T. J. Walsh, The Medicines Company: Consultant and Investigator, Consulting fee and Research grantAstellas: Consultant and Investigator, Consulting fee and Research grant Allergan: Consultant and Investigator, Consulting fee and Research grant Merck: Consultant and Investigator, Consulting fee and Research grant

Non-Diabetic Kidney Disease in Type 2 Diabetic Patients: Prevalence, Clinical Predictors and Outcomes

Background/Aims: Diabetic kidney disease (DKD) is one of the most frequent microvascular complications of diabetes and is the leading cause of end-stage kidney disease worldwide. In patients with diabetes, non-diabetic kidney disease (NDKD) can also occur. NDKD can be either alone or superimposed with the DKD. In this study, we aimed to investigate the utility of kidney biopsy in patients with type 2 diabetes mellitus (T2DM) and the predictability of diagnosing DKD versus NDKD from clinical and laboratory data. We also evaluated the prevalence and etiology of NDKD in patients with T2DM. Methods: We retrospectively reviewed type 2 diabetic patients who had kidney biopsy in the last 10 years for diagnosing possible NDKD in our center. In all patients kidney biopsies were performed because of atypical clinical features and biopsy samples were examined by light and immunofluorescence microscopy. Clinical parameters, laboratory workup and office blood pressures were recorded for each patient at the time of biopsy. Results: Eight patients were excluded due to missing data. A total of 48 patients (female/male: 26/22 and mean age: 59±8 years) were included in the study. According to the biopsy findings, 24 (50%) patients had NDKD alone, 20 (41.7%) had DKD alone and 4 (8.3%) had coexisting DKD and NDKD. The most common NDKD diagnoses were membranous nephropathy (29.2%), tubulointerstitial nephritis (20.8%) and IgA nephropathy (12.5%). There were no significant differences in three groups with respect to the duration of diabetes, proteinuria, hematuria and glycated hemoglobin A1c levels. Diabetic retinopathy (DR) was the most significant finding, which was associated with DKD. Positive and negative predictive values of DR for DKD were 88 and 81%, respectively. Conclusion: This study demonstrated a high prevalence of NDKD in patients with T2DM. The absence of DR strongly predicted NDKD. Clinical decision alone can lead to wrong diagnosis and delay in appropriate therapy. Clinicians should consider the kidney biopsy more liberally when there is uncertainty on the exact etiology of the kidney disease. However, prospective multicenter studies are needed to clarify the prognosis and outcomes of patients with diabetics.

Time Is of the Essence: The Impact of Delayed Antibiotic Therapy on Patient Outcomes in Hospital-Onset Enterococcal Bloodstream Infections.

With increasing prevalence of vancomycin-resistant enterococci (VRE), appropriate antibiotic therapy for enterococcal bloodstream infections (EBSI) can be delayed. Data regarding the impact of delayed therapy on EBSI outcomes are conflicting, and the time delay most strongly associated with poor outcomes has not been defined. This was a single-center, retrospective cohort study of adult, nonneutropenic patients with hospital-onset EBSI from 2010 to 2014. Classification and regression tree (CART) analysis was used to determine the delay in appropriate therapy most predictive of 30-day mortality. Appropriate therapy was defined as antibiotic therapy to which the enterococci and copathogen, where applicable, were susceptible. Outcomes and clinical characteristics were compared between patients receiving early or delayed therapy, defined by CART timepoint. Poisson regression was employed to determine the independent association of delayed therapy on 30-day mortality and predictors of delayed therapy. Overall, 190 patients were included. A breakpoint in time to appropriate therapy was identified at 48.1 hours, where 30-day mortality was substantially increased (14.6% vs 45.3%; P < .001). Patients receiving appropriate therapy after 48.1 hours also experienced higher in-hospital mortality and longer EBSI duration. After adjustment for severity of illness and comorbidity, delayed therapy ≥48.1 hours was associated with a 3-fold increase in 30-day mortality (risk ratio, 3.16 [95% confidence interval, 1.96-5.09]). Vancomycin resistance was the only independent predictor of delayed therapy. In patients with hospital-onset EBSI, receipt of appropriate therapy within the first 48 hours was associated with reduced mortality, underscoring the potential role of rapid diagnostic testing for early identification of VRE.

Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus: Does Vancomycin Heteroresistance Matter?

Vancomycin remains the mainstay treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections, including pneumonia. There is concern regarding the emergence of vancomycin tolerance, caused by heterogeneous vancomycin-intermediate S. aureus (hVISA), and subsequent vancomycin treatment failure. Pneumonia is associated with high morbidity and mortality, especially with delays in appropriate therapy. This study evaluated the clinical outcomes of patients with hVISA pneumonia compared to those with vancomycin-susceptible S. aureus (VSSA) pneumonia. A retrospective cohort of patients with MRSA pneumonia from 2005 to 2014 was matched at a ratio of 2:1 VSSA to hVISA infections to compare patient characteristics, treatments, and outcomes. hVISA was determined by the 48-h population analysis profile area under the curve. Characteristics between VSSA and hVISA infections were compared by univariate analysis and multivariable logistic regression analysis to determine independent risk factors of inpatient mortality. Eighty-seven patients were included, representing 29 hVISA and 58 VSSA cases of pneumonia. There were no significant differences in demographics or baseline characteristics. Sequential organ failure assessment (SOFA) scores were a median of 7 (interquartile ratio [IQR], 5 to 8) in hVISA patients and 5 (IQR, 3 to 8) in VSSA (P = 0.092) patients. Inpatient mortality was significantly higher in hVISA patients (44.8% versus 24.1%; P = 0.049). Predictors of inpatient mortality upon multivariable regression were SOFA score (adjusted odds ratio [aOR], 1.36; 95% confidence interval [CI], 1.08 to 1.70), Panton-Valentine leukocidin (PVL) positivity (aOR, 6.63; 95% CI, 1.79 to 24.64), and hVISA phenotype (aOR, 3.95; 95% CI, 1.18 to 13.21). Patients with hVISA pneumonia experienced significantly higher inpatient mortality than those with VSSA pneumonia. There is a need to consider the presence of vancomycin heteroresistance in pneumonia caused by MRSA in order to potentially improve clinical outcomes.

Legionellosis in Patients With Cancer

Background Legionella species cause severe pneumonia in the immunocompromised population, especially those with cell-mediated immunodeficiency. However, the varied clinical and radiographic presentation of Legionnaires disease can make diagnosis very difficult, which can result in a delay of appropriate therapy. For that reason, we performed this study to review the characteristics of Legionella pneumonia in immunocompromised patients with underlying cancer. Methods The study was a retrospective chart review of 11 patients with Legionella pneumonia at the Moffitt Cancer Center diagnosed between March 2005 and February 2014. The patients were identified on the basis of a positive bronchoalveolar lavage culture for Legionella and/or a positive Legionella urine antigen. Summarized host characteristics included underlying malignancy, absolute neutrophil count, and absolute lymphocyte count at the time of diagnosis as well as the computed tomographic chest imaging findings. Results Of the 11 patients included, 10 had Legionella pneumophila and 1 had L. feeleii. Nine (81.8%) of the 11 patients had a hematologic malignancy and 2 (18.2%) of the 11 patients had a solid organ tumor. One (9.0%) of the 11 patients had an underlying lung disease. At the time of the diagnosis, 3 (27.2%) of the 11 patients were neutropenic (absolute neutrophil count, <500 cells/mm3) and 8 (72.7%) of the 11 patients were lymphopenic (absolute lymphocyte count, <1500 cells/mm3). Four (36.3%) of the 11 patients had bilateral pneumonia. Three (27.2%) of the 11 patients had nodular consolidation. However, only 2 (18%) of the 11 patients were found to have consolidation along with ground-glass opacity. All patients were treated with levofloxacin. Seven (63.6%) of the 11 patients adequately responded to the therapy, 1 (9.0%) patient died because of pneumonia, and 3 (27.3%) patients died because of the underlying cancer. Conclusions Legionnaire disease remains a life-threatening illness in patients with cancer. Our study found that most patients are lymphopenic, with multifocal consolidation in 2 of 3 patients. In addition, nodular opacities on computed tomographic imaging were described in more than one third of our patients, which resembles a mold pneumonia. All the cases that were thought to be a mold pneumonia were diagnosed as Legionella by bronchoalveolar lavage culture or the Legionella urine antigen, emphasizing the need for heightened awareness and testing for this pathogen.

Stroke and Stroke Mimics: A case of High-grade glioma

The clinical diagnosis of acute stroke is inaccurate approximately 10%-30% of the time, which can lead to unnecessary administration of thrombolytic therapy or delays in appropriate therapy. Rapid and accurate neuroimaging triage is essential to guide therapy and exclude mimics. Although many conditions that mimic stroke clinically have imaging appearances that can overlap acute stroke, these conditions can be differentiated in most cases by using a careful pattern-based approach. We describe a case of 67 yo male patient who had a clinic of wakeup stroke and at the first magnetic resonance image (MRI) it was found that was an acute stroke of middle cerebral artery.The patient did not improve and a second MRI revelead a two times growth of the lesion, and the MRI findings were compatible with tumor. At the surgery they found a infiltrative lesion and the anatomopathological exam showed that it was a high grade glioma.The diagnosis of ischemic stroke is often straight forward; however, the clinical diagnosis of acute stroke is inaccurate in many cases. Furthermore, many of these conditions, such as encephalitis, mass lesions, seizures, hypoglycemia, transient global amnesia (TGA),demyelinating disease, drug toxicity, and metabolic disturbances, have imaging appearances that can mimic acute or subacute infarction; however, an accurate diagnosis can often be made by using a pattern-based approach.