Intravenous Vancomycin Research Articles

Abstract 15682: A Novel Antibiotic Delivery Approach Enhances Salvage of Infected Cardiovascular-implantable Electronic Devices

Introduction: Infection of cardiovascular-implantable electronic devices (CIED) is a serious complication. Systemic antibiotic therapy is considered ineffective, justifying the current guidelines proposing total CEID and lead extraction. Objective: To evaluate the safety and efficacy of continuous in-situ-targeted, ultra-high concentration of antibiotics (CITA) in CIED infections limited to the subcutaneous pocket. Methods: Infected CIED were treated with CITA, delivered to the CIED pocket following minimally invasive surgery (MIS). The CIED were submerged in a 10 2 -10 3 minimal inhibition concentration (MIC) solution of vancomycin and/or gentamicin as per daily conventional dosing. Serum antibiotic levels were regulated by adjusting the concentration and flow of pocket irrigation. CIED salvage rate was assessed. Results: A total of 937 and 481serum assays of vancomycin and gentamicin, respectively, from 83 infected CIED was evaluated (Figure). Target antibiotic serum levels were obtained at 12-48 hours. Median treatment was 8 days (IQR 5,12). Parallel intravenous (IV) vancomycin treatment was applied in 6 (7%) infections. Vancomycin serum levels exceeded a trough limit of 20μg/ml in 20 (2.1%) assays, of which 19/20 received parallel IV treatment. No peak gentamicin levels were recorded. Gentamicin exceeded trough serum level reaching 2-3μg/ml in 80 (16.6%), reached potentially toxic levels of 3-5μg/ml in 33 (6.9%), and exceeded 5μg/ml in 10 (2.1%) assays. CITA resulted in a 1-year salvage of 71 (86%) CIED. Treatment failed in 12 infections, resulting in 8 uneventful total CIED extractions. The 30-day mortality rate was 2.4%. Conclusions: CITA provided ultra-high pocket antibiotic levels, with its safety confirmed by systemic level assays. CITA combined with MIS enabled salvage of 86% of infected CIED. The CITA-MIS approach may serve as an initial therapeutic option prior to the extraction of locally infected CIED, especially in high-risk patients.

Vancomycin Serum Concentration after 48 h of Administration: A 3-Years Survey in an Intensive Care Unit.

The present study assessed the proportion of intensive care unit (ICU) patients who had a vancomycin serum concentration between 20 and 25 mg/L after 24–48 h of intravenous vancomycin administration. From 2016 to 2018, adult ICU patients with vancomycin continuous infusion (CI) for any indication were included. The primary outcome was the proportion of patients with a first-available vancomycin serum concentration between 20–25 mg/L at 24 h (D2) or 48 h (D3). Of 3894 admitted ICU patients, 179 were included. A median loading dose of 15.6 (interquartile range (IQR) = (12.5–20.8) mg/kg) was given in 151/179 patients (84%). The median daily doses of vancomycin infusion for D1 and D2 were 2000 [(IQR (1600–2000)) and 2000 (IQR (2000–2500)) mg/d], respectively. The median duration of treatment was 4 (2–7) days. At D2 or D3, the median value of first serum vancomycin concentration was 19.8 (IQR (16.0–25.1)) with serum vancomycin concentration between 20–25 mg/L reported in 43 patients (24%). Time spent in the ICU before vancomycin initiation was the only risk factor of non-therapeutic concentration at D2 or D3. Acute kidney injury occurred significantly more when vancomycin concentration was supra therapeutic at D2 or D3. At D28, 44 (26%) patients had died. These results emphasize the need of appropriate loading dose and regular monitoring to improve vancomycin efficacy and avoid renal toxicity.

Comparison of trough concentration and area under the curve of vancomycin associated with the incidence of nephrotoxicity and predictors of a high trough level

PurposeA high vancomycin trough concentration during therapy is associated with increased nephrotoxicity, and the recent guidelines for therapeutic monitoring of vancomycin recommend target of the ratio of area under the curve (AUC) to minimum inhibitory concentration. We aimed to determine vancomycin trough concentration and AUC that induce nephrotoxicity and evaluate predictive factors associated with a high serum vancomycin trough level according to the initial dosing strategy. MethodsWe conducted a retrospective cohort study in patients administered intravenous vancomycin from June 2013 to February 2017. Totally, 346 patients were included. Results38 experienced nephrotoxicity during therapy. The both trough level and AUC were significant risk factors for the occurrence of vancomycin induced-nephrotoxicity (p < 0.001, p = 0.001). The exposure–response analysis revealed that the trough level of 15 μg/mL was associated with 12.0% nephrotoxicity incidence and AUC of 600 was associated with 12.9% nephrotoxicity incidence. During the treatment, 90 patients had an initial trough concentration of ≥15 μg/mL, and 124 patients had AUC of ≥600 μg h/mL. The multiple logistic regression analysis revealed body weight (p = 0.001), serum creatinine level (p = 0.028), daily vancomycin dose (p = 0.001), and ICU (p = 0.015) were independent predictive factors for a high trough concentration. And same factors were selected for the high AUC. ConclusionThe risk factors for vancomycin induced nephrotoxicity were comparable in both trough concentration and AUC. The incidence of nephrotoxicity can be reduced by controlling vancomycin trough concentration similarly AUC and promoting antimicrobial stewardship.

Prediction of Vancomycin Levels Using Cystatin C in Overweight and Obese Patients: a Retrospective Cohort Study of Hospitalized Patients.

The use of the kidney function biomarker cystatin C (cysC) can improve the accuracy of vancomycin dosing for target trough attainment in nonobese patients. It is unknown whether cysC can also improve vancomycin target trough attainment in overweight and obese patients. We conducted a retrospective observational study of overweight or obese hospitalized adults with stable renal function administered intravenous vancomycin between January 2011 and July 2019. Linear regression models were used to predict initial steady-state vancomycin troughs using several factors, including various cysC- and serum creatinine (SCr)-based estimates of kidney function. We compared the predicted proportion of patients within the target trough range (10 to 20 mg/liter) using the derived models to that observed from usual care. Of the 200 included patients, the mean trough level was 15 ± 6.3 mg/liter. The optimal model to predict the initial trough included both cysC and SCr (R2 = 0.48) rather than either biomarker alone. This model predicted that 79% (95% confidence interval [CI], 73% to 85%) of troughs could be between 10 and 20 mg/liter compared to the 62% observed in clinical practice (P < 0.001), a 1.3-fold increase. This study is the first to examine the role of cysC in predicting vancomycin levels in an exclusively overweight or obese population. While dosing models based on cysC appear promising in this setting, prospective validation is needed.

The comparative risk of acute kidney injury of vancomycin relative to other common antibiotics

The glycopeptide antibiotic vancomycin is a mainstay in the treatment of Gram-positive infection. While its association with acute kidney injury (AKI) has waxed and waned, recent data suggest nephrotoxicity, even as mono-therapy. Our study aimed to evaluate the 2-week risk of AKI after at least 3 days of intravenous vancomycin mono-therapy initiated within 5 days of hospitalization compared to other intravenous antibiotics used for similar indications. We used a new user-active comparator study design and identified patients with a first hospitalization during which they received vancomycin or comparator, from commercial claims based in the United States. We estimated incidence rates, hazard ratios using adjusted cox-regression models, and standardized mortality/morbidity ratio weighted cox-regression models. In the 32,997 patients vancomycin was used in 17% of patients and 129 cases of AKI were observed. Overall incidence of AKI was 9.3 (95% CI 0.78–1.22) per 100 person-years. The adjusted hazard ratio for vancomycin versus all other comparators was 0.74 (95% CI 0.45–1.21). Separate models for respective comparators resulted in hazard ratios below the null, except for vancomycin vs. cefazolin. Intravenous vancomycin mono-therapy does not increase the risk of AKI compared to other intravenous antibiotics used for similar indication in this cohort of hospitalized patients.

Population Pharmacokinetics of Vancomycin in Kidney Transplant Recipients: Model Building and Parameter Optimization.

BackgroundDepending on the renal function of patients and many other influencing factors, studies on vancomycin pharmacokinetics show significant inter- and intra-individual variability. The present study was conducted using a population pharmacokinetics method to investigate the pharmacokinetic parameters and identified their influencing covariates for intravenous vancomycin in adult kidney transplant recipients.MethodsThe drug monitoring data included 56 adult renal transplant recipients who received intravenous vancomycin as prophylactic medication. The analysis was performed by a population approach with NONMEM. Data were collected mainly during the first week after transplantation. Monitoring of vancomycin trough concentration in blood was initiated mainly 3–5 days after the initial administration.ResultsThe one-compartment open model was optimal and adequately described the data. Body weight (WT) and estimated glomerular filtration rate (GFR) were identified as significant covariates of the pharmacokinetic parameters CL and V of intravenous vancomycin in the kidney transplant patients. The typical values of vancomycin CL and V were 2.08 L h-1 and 63.2 L, respectively. A dosage strategy scheme according to model results was also designed.ConclusionBoth WT and GFR of the kidney transplant patients positively influence the pharmacokinetic parameters CL and V for intravenous vancomycin. Our population pharmacokinetic model provides a reference for vancomycin dosage adjustment in kidney transplant recipients.

NOCARDIOSIS PRESENTING LIKE A METASTATIC LUNG CANCER

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Nocardia is a gram-positive, weakly acid-fast, branching rod which is ubiquitous environmental saprophytes that cause localized or disseminated disease in both immunocompetent and immunocompromised patients. We present here a case of a 55-year-old male who was found to have right middle lobe lung abscess as well as right cerebellar abscess secondary to disseminated Nocardiosis from the pulmonary source. CASE PRESENTATION: A 55-year-old male with a past medical history of hypertension, hyperlipidemia, migraines, 30 pack-year smoking history, and emphysematous COPD presented to the hospital with 5 days of cough productive of clear sputum, headache and multiple episodes of emesis. He also reported 30 pounds weight loss over the last 1 year due to poor appetite. On presentation, he was hypoxic and tachypneic requiring 5 liters of oxygen by nasal cannula. Physical examination showed a cachectic male with decreased breath sounds bilaterally and crackles in the right lower lung field. The neurological exam showed nystagmus with right-sided gaze and square wave jerks as well as dysdiadochokinesia. Labs showed elevated WBC count at 17.6*10^3 with Neutrophilic pleocytosis. Chest CT showed right middle lobe lung mass, multiple bilateral pulmonary nodules as well as right lower lobe pneumonia. CT head showed right-sided cerebellar mass. Hence an emergent MRI was obtained to assess the mass which showed a large multiseptated cerebellar mass measuring 4.7 * 5.8 * 3.2 cm with mild vasogenic edema centered in the right cerebellar hemisphere crossing midline and producing severe stenosis of the fourth ventricle and resultant obstructive hydrocephalus. The patient was taken to the Operating room STAT and when the right cerebellum was entered a green-tinged fluid started draining which was sent for a culture that grew Nocardia cyriacigeorgica. The patient also had a bronchoscopic biopsy of the right-sided lung mass a day later which also grew the same organism. The patient was initially treated with Intravenous vancomycin, ceftriaxone and levofloxacin for broad-spectrum coverage for pneumonia and after the cultures grew Nocardia was switched to intravenous trimethoprim-sulfamethoxazole and meropenem after infectious disease consultation. However, he failed to respond to the therapy and was made comfort care and passed away. DISCUSSION: Disseminated disease with Nocardia involving brain and lung has been reported in both immunocompromised and immunocompetent patients. However, most of the cases reported in the literature are of elderly patients or immunocompromised patients. As the population of the United States is aging with many patients on immunomodulators it is imperative to raise awareness about disseminated nocardiosis CONCLUSIONS: Physicians must be aware that disseminated nocardiosis can mimic the presentation of metastatic lung carcinoma: early surgical intervention in brain abscess improves outcomes. Reference #1: Karan M, Vučković N, Vuleković P, Rotim A, Lasica N, Rasulić L. Acta Clin Croat. 2019 Sep;58(3):540-545. doi: 10.20471/acc.2019.58.03.20. Reference #2: Schlaberg R, Huard RC, Della-Latta P. Nocardia cyriacigeorgica, an emerging pathogen in the United States. J Clin Microbiol. 2008. Jan;46(1):265–73. 10.1128/JCM.00937-07 Reference #3: Lee GY, Daniel RT, Brophy BP, Reilly PL. Surgical treatment of nocardial brain abscesses. Neurosurgery. 2002. Sep;51(3):668–71, discussion 671–2. 10.1097/00006123-200209000-00010 DISCLOSURES: No relevant relationships by Fazal Raziq, source=Web Response No relevant relationships by Muhammad Usama, source=Web Response

Appropriateness of Anti-MRSA Therapy in Hospitalized Patients With Suspected Community-Onset Infections

Background: Inappropriate use of MRSA-spectrum antibiotics is an important antimicrobial stewardship target. Contributors to inappropriate use include empiric treatment of patients who are determined to not be infected or who are infected but lack MRSA risk factors, and by excessive treatment duration when suspected MRSA infection is disproven. To characterize opportunities for improvement, we conducted a medical use evaluation (MUE) in 27 VA medical centers. The primary objectives were to assess the following proportions: (1) courses of unjustified empiric vancomycin therapy (patients in whom all antibacterials were halted within 2 days or without a principal or secondary discharge infection diagnosis); (2) courses of unjustified continuation of anti-MRSA therapy beyond day 4 (no MRSA risk factors or proven MRSA infection); and (3) excess anti-MRSA days of therapy (DOT), that is, DOT in unjustified empiric courses plus DOT after day 4 in unjustified continued courses. Methods: Clinical pharmacists performed retrospective, structured, manual record reviews of patients started on intravenous vancomycin on day 1 or 2 of hospitalization from June 2017 to May 2018. Exclusion criteria included surgical prophylaxis, recent MRSA infection, β-lactam allergy, renal insufficiency, severe immunosuppression, or infection that warranted anti-MRSA therapy other than vancomycin. Results: Of 2,493 evaluated patients, 1,320 met the inclusion criteria. Among them, 44% of courses were initiated in the emergency department, 37% of patients had ≥1 risk factor for healthcare-associated infections, and 50% of patients had ≥2 SIRS criteria or required vasopressor support. The most common admission diagnoses were skin and soft-tissue infection (SSTI, 40%; 68% nonpurulent) and pneumonia (27%; 46% without healthcare risk factors). Clinical cultures recovered MRSA from 8% of patients. Empiric therapy was not justified in 342 patients (26%; 57% were clinically stable). Continued therapy was unjustified in 46% of the 320 patients who received &gt;4 days of anti-MRSA therapy. Of all days of anti-MRSA therapy, 23% were unjustified; 65% of these were due to unjustified empiric therapy. Site-specific variations in unjustified empiric therapy better correlated with the proportion of unjustified DOT than did unjustified continuation of therapy (Pearson correlation coefficients [PCC], 0.75 and 0.54, respectively) (Fig. 1). Facility-specific proportions of unjustified DOT modestly correlated with anti-MRSA DOT (PCC, 0.45; n = 27) (Fig. 2) but not the anti-MRSA standardized antimicrobial administration ratio (PCC, 0.15; n = 21). Conclusions: In this multicenter MUE, 26% of all days of anti-MRSA therapy lacked justification; this rate correlated with total facility-specific anti-MRSA DOT. Unnecessary empiric therapy, largely in the ED and for nonpurulent SSTIs and pneumonia without risk factors, was the principal contributor to unjustified DOT.Funding: NoneDisclosures: None

Hospital Microbiologic Culture Results to Predict the Use of Anti–methicillin-Resistant Staphylococcus aureus (MRSA)

Background: To provide a standardized, risk-adjusted method for summarizing antimicrobial use (AU), the Centers for Disease Control and Prevention developed the standardized antimicrobial administration ratio, an observed-to-predicted use ratio in which predicted use is estimated from a statistical model accounting for patient locations and hospital characteristics. The infection burden, which could drive AU, was not available for assessment. To inform AU risk adjustment, we evaluated the relationship between the burden of drug-resistant gram-positive infections and the use of anti-MRSA agents. Methods: We analyzed data from acute-care hospitals that reported ≥10 months of hospital-wide AU and microbiologic data to the National Healthcare Safety Network (NHSN) from January 2018 through June 2019. Hospital infection burden was estimated using the prevalence of deduplicated positive cultures per 1,000 admissions. Eligible cultures included blood and lower respiratory specimens that yielded oxacillin/cefoxitin–resistant Staphylococcus aureus (SA) and ampicillin-nonsusceptible enterococci, and cerebrospinal fluid that yielded SA. The anti-MRSA use rate is the total antimicrobial days of ceftaroline, dalbavancin, daptomycin, linezolid, oritavancin, quinupristin/dalfopristin, tedizolid, telavancin, and intravenous vancomycin per 1,000 days patients were present. AU rates were modeled using negative binomial regression assessing its association with infection burden and hospital characteristics. Results: Among 182 hospitals, the median (interquartile range, IQR) of anti-MRSA use rate was 86.3 (59.9–105.0), and the median (IQR) prevalence of drug-resistant gram-positive infections was 3.4 (2.1–4.8). Higher prevalence of drug-resistant gram-positive infections was associated with higher use of anti-MRSA agents after adjusting for facility type and percentage of beds in intensive care units (Table 1). Number of hospital beds, average length of stay, and medical school affiliation were nonsignificant. Conclusions: Prevalence of drug-resistant gram-positive infections was independently associated with the use of anti-MRSA agents. Infection burden should be used for risk adjustment in predicting the use of anti-MRSA agents. To make this possible, we recommend that hospitals reporting to NHSN’s AU Option also report microbiologic culture results.Funding: NoneDisclosures: None

S2781 A Case of Clostridium difficile Enteritis

INTRODUCTION: Clostridium difficile (C. difficile) is the cause of 20–25% of antibiotic-associated diarrhea. Extracolonic manifestations of C. difficile are rare but include osteomyelitis and reactive arthritis. More rarely, the bacteria can colonize the small bowel and cause active small bowel enteritis with mortality reported as high as 25%. We present a case of C. difficile enteritis. CASE DESCRIPTION/METHODS: A 39-year-old woman with history of alcoholic liver cirrhosis and splenic embolization for thrombocytopenia one week prior to presentation was admitted for abdominal pain after paracentesis. Her labs were notable for leukocytosis, thrombocytopenia, elevated lactate and elevated INR. Computed-tomography of the abdomen revealed thickening of the proximal small bowel and right colon consistent with enterocolitis, splenomegaly and ascites. Ultrasound showed portal vein thrombosis. Her course was complicated by hepatic encephalopathy and spontaneous bacterial peritonitis. She was transferred to the intensive care unit and an indwelling intraperitoneal catheter was inserted to drain the ascites. The WBC of the peritoneal fluid peaked at 55,000/ml and cultures grew C. difficile. The serum WBC peaked at 66,500/ml and blood cultures also grew C. difficile. Stool was positive for toxigenic C. difficile PCR. Oral vancomycin, intravenous vancomycin and intravenous metronidazole were started. On the 10th day of admission, a donor liver became available and she was taken to the operating room (OR) for transplant. Multiple splenic and intra-abdominal abscesses were noted during the exploration phase of surgery and the surgery was cancelled. Decision was made to take the patient back to the OR for abdominal wash out and possible splenectomy. Unfortunately, she had cardiac arrest intraoperatively and expired after failed resuscitative efforts. DISCUSSION: The exact pathophysiology of C. difficile enteritis is not well-understood, especially in patients with intact small bowel. Majority of patients had prior gastrointestinal surgery such as colectomy. Our patient, however, had no prior abdominal surgeries or intervention. We presume that as a complication of her splenic embolization and raging peritonitis, she developed a portal vein thrombosis causing small bowel wall edema, allowing for translocation of C. difficile from her bloodstream into her small bowel and peritoneal cavity. There must be a high index of suspicion for C. difficile enteritis, as it is not a common entity and has a high mortality rate.

De-escalation of Antibiotics in Severe Sepsis and Septic Shock at a Large Municipal Hospital

Background: Early de-escalation of antibiotics in sepsis may be safe and effective. In our study, we performed a retrospective chart review of patients admitted to a large municipal hospital who were treated for severe sepsis or septic shock to compare outcomes in patients who experienced early de-escalation (DEG) with outcomes of those who did not (NDG).Methods: The observational study was conducted at Bellevue Hospital Center (an 850-bed municipal hospital affiliated with New York University School of Medicine, New York, NY). Patients admitted from January 1 to December 31, 2015, who were treated for severe sepsis or septic shock during any time of their hospital stay were reviewed for the study. De-escalation was defined as narrowing or discontinuation of 1 or more antimicrobial therapies &lt; 3 days after sepsis onset. Results: Overall, 277 patients were included (DEG, 90 patients, 32%; NDG, 187 patients, 68%). The groups were similar in terms of sex, comorbidities, length of stay, and severity of illness: septic shock (47% DEG vs 49% NDG; P = .693) and ICU stay (27% DEG vs 32% NDG; P = .406). DEG patients were slightly older than NDG patients: (DEG age, 63+16 years vs NDE age, 58+16 years; P = .028). There was no difference in hospital mortality (8% DEG vs 12% NDE; P = .257). Nearly half of the patients in both groups (46% DEG and 47% NDG) had no causative microorganisms identified using conventional microbiology culture. The common sources of primary infection were respiratory, urinary tract, and gastrointestinal infections, and these were not different between groups. Also, 69% of DEG patients and 79% of NDG patients received antibiotics for &gt;7 days (P = .002). Empiric intravenous vancomycin was initiated in 83% in DEG patients and 74% in NDG patients at sepsis diagnosis. Although organisms covered by intravenous vancomycin were isolated from only 17% of patients in DEG and 23% in NDG, vancomycin was continued for &gt;5 days in 34% of DEG patients and 50.3% of NDG patients (P &lt; .001). 60% of patients in DEG and 61% in NDG were seen by infectious diseases specialists (ID). Patients with infectious diseases consultations had significantly more comorbidities, were more frequently in the ICU, had higher MDRO isolation and longer hospital stays, but they were still de-escalated without a difference in mortality. Conclusions: Microbiology data did not contribute to early de-escalation of antibiotics in this study. This finding may be related to the high percentage of negative culture and unavailability of rapid molecular diagnostic tests. Shorter duration of antibiotics (including vancomycin) was not associated with worse outcome in these severely ill patients.Funding: NoneDisclosures: None

AN UNUSUAL CASE OF TRICUSPID VALVE INFECTIVE ENDOCARDITIS CAUSED BY ERYSIPELOTHRIX RHUSIOPATHIAE

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Erysipelothrix rhusiopathiae is an uncommon cause of endocarditis. We present a case of Erysipelothrix rhusiopathiae in a patient with tricuspid valve involvement. CASE PRESENTATION: This is a 47-year-old male with a history of hypertension who presented with a four-week history of bilateral lower extremity edema. The patient is a lumberjack by occupation and was having difficulty working. His swelling extended to his knees, prompting a visit to his primary physician. The patient was started on oral furosemide but reported no improvement. On admission, the patient was afebrile. The patient was fluid overloaded with bibasilar lung crackles and 3+ pitting edema in bilateral lower extremities. Labs revealed leucocytosis, creatinine of 3.8, and an NT-pro-BNP level of 29,959. CT of the chest revealed pulmonary edema. The patient was started on intravenous diuretic therapy and oral beta-blockers in view of his acute decompensated heart failure. The patient's blood cultures were positive for gram-positive rods and started on empiric treatment with intravenous vancomycin. Echocardiogram revealed severe tricuspid regurgitation and multiple tricuspid valve vegetations. The most significant vegetation was noted to be 2.6 cm x 1.6 cm in size. A trans-esophageal echocardiogram revealed severe tricuspid regurgitation with significant vegetations visible on all three leaflets of the tricuspid valve. After 6 days, repeat blood cultures showed gram-positive rods with sensitivities revealing Erysipelothrix rhusiopathiae as the causative agent. The patient's antibiotic regimen was converted to intravenous Penicillin G. DISCUSSION: Erysipelothrix rhusiopathiae is a gram-positive, rod-shaped, non-sporing bacillus. It is a zoonotic disease known for its association with occupations involving close exposure to animals [1]. Patients who are diagnosed with this infection manifest with skin infections or systemic organ involvement. Our patient presented with systemic bacteremia, with common involvement of the aortic valve [1]. The clinical presentation of our patient was unique, given that in the absence of heart disease, he presented with overt volume overload and acute renal failure. He lacked the more classic symptoms of infective endocarditis, including fever, chills, and skin lesions. Our patient did not have any significant past medical conditions increasing his risk for infective endocarditis. In past literature, reported cases of Erysipelothrix rhusiopathiae and endocarditis had shown a proclivity towards the aortic valve [1,2]. In our case, we felt the most astonishing feature was the isolated involvement of the tricuspid valve. Its mortality rate is higher when compared to the more common etiological pathogens of infective endocarditis [1]. CONCLUSIONS: Physicians should not only observe clinical symptoms but aim to holistically assess the patient to reach a timely diagnosis and initiate appropriate therapy. Reference #1: Reboli, A.C. and W. Farrar, Erysipelothrix rhusiopathiae. Principles and practice of infectious diseases, 2010. 5: p. 2226-7. Reference #2: Veraldi, S., et al., Erysipeloid: a review. Clinical and Experimental Dermatology: Clinical dermatology, 2009. 34(8): p. 859-862. DISCLOSURES: No relevant relationships by Karthik Gonuguntla, source=Web Response No relevant relationships by Pranav Karambelkar, source=Web Response No relevant relationships by Shivaraj Patil, source=Web Response No relevant relationships by Chaitanya Rojulpote, source=Web Response

Impact of Screening for Methicillin-Resistant Staphylococcus aureus (MRSA) in Pneumonia on Vancomycin Utilization

Background: Methicillin-Resistant Staphylococcus aureus (MRSA) is frequently targeted with empiric treatment for pneumonia in the hospital. Obtaining quality lower respiratory tract cultures to promote appropriate de-escalation can be difficult or impractical. Nasal screening for MRSA has a high negative predictive value for MRSA pneumonia and can be an effective tool for early de-escalation. Methods: A pharmacist-driven process for nasopharyngeal MRSA screening of patients prescribed intravenous vancomycin was implemented in October 2018. Vancomycin utilization was extracted from the electronic medical record (EMR) and summarized as days of therapy per 1,000 patient days (DOT/1,000 PD). Vancomycin utilization data for the 6 months following process implementation (November 2018–April 2019) were compared to the same period from the previous year (November 2017–April 2018). Specific patient outcomes data were manually collected for patients prescribed vancomycin for pneumonia during the first 2 months following process implementation (November–December 2018; postintervention group) and comparable months (November–December 2017; preintervention group). Data were analyzed using the 2 test (nominal data) and Mann–Whitney U test (continuous data). Results: Total vancomycin utilization decreased from a monthly average of 114 to 95 DOT/1,000 PD (17% reduction) and from 27 to 14 DOT/1,000 PD for pneumonia (48% reduction). In-patient mortality was unchanged following process implementation at 17.2% versus 17.5% in the pre- and postintervention groups, respectively. Other clinical outcomes were also similar between the pre- and postintervention groups (Table 1). Fewer vancomycin levels were obtained following implementation with 34.4% of patients (0.61 levels per patient) having a level obtained in the preintervention group compared to 21.6% (0.30 levels per patient; P .001) in the postintervention group. Conclusions: Nasopharyngeal MRSA screening of patients prescribed vancomycin for pneumonia is an effective antimicrobial stewardship strategy to reduce unnecessary use of anti-MRSA therapy without negatively impacting clinical outcomes.Funding: NoneDisclosures: None

Vancomycin in ICU Patients with Gram-Positive Infections: Initial Trough Levels and Mortality.

BackgroundVancomycin is one of the most common therapeutic agents for treating gram-positive infections, particularly in critically ill patients. The aim of this study was to identify factors associated with initial therapeutic vancomycin trough levels and mortality in a tertiary-care intensive care unit (ICU).MethodsThis retrospective study evaluated 301 adult ICU patients admitted to King Abdulaziz Medical City in Riyadh between October 1, 2017 and December 31, 2018 with confirmed gram-positive infections and received intravenous vancomycin. Vancomycin trough levels of 15–20 mg/L for severe infections and 10–15 mg/L for less severe infections were considered therapeutic.ResultsThe patients were relatively older with a mean age of 60 (SD ±20) years. Initial vancomycin trough levels were therapeutic in 168 (55.8%). Factors associated with initial therapeutic vancomycin trough levels were female gender (adjusted odds ratio [aOR]=2.575), older age (aOR=1.024), receiving a loading dose (aOR=2.445), having bacteremia (aOR=2.061), and high platelet count (aOR=1.003). On the other hand, the increase of estimated glomerular filtration rate (eGFR) (aOR=0.993) and albumin levels (aOR=0.944) were associated with lower odds of initial therapeutic vancomycin trough levels. Factors associated with higher mortality were female gender (adjusted hazard ratio [aHR]=2.630), increased body weight (aHR=1.021), cancer (aHR=3.451), and high APACHE II score (aHR=1.068).ConclusionThe study identified several factors associated with achieving initial therapeutic vancomycin trough levels (i.e. older age, female gender, receiving a loading dose, bacteremia, high platelets count, low eGFR and albumin level). These factors should be considered in the dosing of vancomycin in critically ill patients with gram-positive infections.

Post-procedural Bacillus cereus septic arthritis in a patient with systemic lupus erythematosus.

IntroductionBacillus species are often considered as contaminants when cultured from clinical samples. Bacillus cereus may be a pathogen in certain circumstances and is known to cause musculoskeletal infections. This report aims to educate clinicians and clinical microbiology laboratories on B. cereus musculoskeletal infections and to heighten awareness that Bacillus species should not always be dismissed as contaminants.Case presentationWe report the case of a patient who presented to a tertiary hospital in Pretoria, South Africa, in November 2018 with B. cereus septic arthritis and underlying systemic lupus erythematosus (SLE). The isolate would otherwise have been dismissed as a contaminant had it not been for the crucial interaction between the laboratory and the treating clinicians. To our knowledge, this is the first case report of septic arthritis caused by B. cereus in an SLE patient where the organism was cultured from the joint specimen. Identification of the organism was performed using matrix-assisted laser desorption/ionisation mass spectrometry.Management and outcomeDefinitive treatment was with intravenous vancomycin, continued for four weeks, in addition to arthroscopy and management of the underlying SLE. The patient had a good clinical outcome and regained full mobility.ConclusionMusculoskeletal infections, specifically septic arthritis caused by B. cereus, are exceedingly rare infections. Immune suppression, trauma, prosthetic implants and invasive procedures are important risk factors for B. cereus musculoskeletal infections. Close collaboration with a multi-disciplinary team approach will effect the best outcome for complicated patients with B. cereus infections.

Assessing the accuracy of two Bayesian forecasting programs in estimating vancomycin drug exposure.

Current guidelines for intravenous vancomycin identify drug exposure (as indicated by the AUC) as the best pharmacokinetic (PK) indicator of therapeutic outcome. To assess the accuracy of two Bayesian forecasting programs in estimating vancomycin AUC0-∞ in adults with limited blood concentration sampling. The application of seven vancomycin population PK models in two Bayesian forecasting programs was examined in non-obese adults (n = 22) with stable renal function. Patients were intensively sampled following a single (1000 mg or 15 mg/kg) dose. For each patient, AUC was calculated by fitting all vancomycin concentrations to a two-compartment model (defined as AUCTRUE). AUCTRUE was then compared with the Bayesian-estimated AUC0-∞ values using a single vancomycin concentration sampled at various times post-infusion. Optimal sampling times varied across different models. AUCTRUE was generally overestimated at earlier sampling times and underestimated at sampling times after 4 h post-infusion. The models by Goti et al. (Ther Drug Monit 2018. 212-21) and Thomson et al. (J Antimicrob Chemother 2009. 1050-7) had precise and unbiased sampling times (defined as mean imprecision <25% and <38 mg·h/L, with 95% CI for mean bias containing zero) between 1.5 and 6 h and between 0.75 and 2 h post-infusion, respectively. Precise but biased sampling times for Thomson et al. were between 4 and 6 h post-infusion. When using a single vancomycin concentration for Bayesian estimation of vancomycin drug exposure (AUC), the predictive performance was generally most accurate with sample collection between 1.5 and 6 h after infusion, though optimal sampling times varied across different population PK models.

Staphylococcal endocarditis in a quadricuspid aortic valve following uncomplicated dengue infection: a case report

BackgroundDengue fever is endemic and a leading health problem in Sri Lanka. Increased incidence of concurrent bacteremia in patients with dengue infection is a recognized complication. However, Staphylococcal endocarditis following dengue fever is uncommon. Quadricuspid aortic valve (QAV) is a rare congenital anomaly and few cases of infective endocarditis have been reported in QAV.Case presentationA 32-year-old Sri Lankan male presented to the National Hospital of Sri Lanka with recurrence of fever and acute left hemiplegia following an uncomplicated recovery of dengue fever. He was diagnosed to have Staphylococcal infective endocarditis of quadricuspid aortic valve, with septic emboli to brain and spleen. He was managed with intravenous vancomycin initially, however, due to inadequate response, intravenous linezolid was added. He developed rhabdomyolysis with very high creatine phosphokinase leading to acute kidney injury, which settled with the cessation of linezolid. The patient succumbed to his illness despite aggressive antimicrobial therapy and maximum supportive care while being assessed for aortic valve replacement.ConclusionsThis case illustrates three clinical issues that a clinician should be aware of. Firstly, the possibility of a serious secondary bacterial infection as a cause for recurrence of fever following dengue infection. Secondly, this case highlights the importance of identifying QAV as a cause for complicated infective endocarditis of increased severity. The report also denotes the value of being vigilant of linezolid induced rhabdomyolysis which had a causal relationship with the commencement of the drug and its cessation.

Delafloxacin: A Review in Acute Bacterial Skin and Skin Structure Infections.

The global spread of antibacterial-resistant strains, especially methicillin-resistant Staphylococcus aureus (MRSA) for acute bacterial skin and skin structure infections (ABSSSIs), has driven the need for novel antibacterials. Delafloxacin [Quofenix™ (EU); Baxdela® (USA)], a new fluoroquinolone (FQ), has a unique chemical structure that enhances its antibacterial activity in acidic environments such as occurs in ABSSSIs (including S. aureus infections). Delafloxacin (intravenous and oral formulations) is approved in several countries for the treatment of adults with ABSSSIs (featured indication). In intent-to-treat analyses in pivotal phase 3 trials in adults with ABSSSIs, including those with comorbid disease, intravenous delafloxacin monotherapy (± oral switch after six doses) twice daily was noninferior to intravenous vancomycin + aztreonam for primary endpoints, as specified by the FDA (objective response rate at 48–78 h after initiation of therapy) and the EMA [investigator-assessed clinical cure rate at the follow-up visit at day 14 (± 1 day)]. Delafloxacin was generally well tolerated, with most treatment-related adverse events mild to moderate in severity and few patients discontinuing treatment because of these events. Relative to vancomycin + aztreonam (a non-FQ regimen), delafloxacin treatment was not associated with an increased risk of FQ-associated AEs of special interest. Given its unique chemical structure that confers novel properties relative to other FQ and its broad spectrum of activity against common clinically relevant Gram-positive pathogens, including against MRSA strains (± FQ-resistance mutations), and Gram-negative pathogens, intravenous delafloxacin (± oral switch) provides a novel emerging option for the treatment of adult patients with ABSSSIs.

Baseline Characteristics and Outcomes Among Patients with Complicated Skin and Soft Tissue Infections Admitted to the Intensive Care Unit: Analysis of the Phase 3 COVERS Randomized Trial of Ceftaroline Fosamil Versus Vancomycin Plus Aztreonam.

AimExploratory analyses evaluated patient characteristics and outcomes among patients with complicated skin and soft tissue infection (cSSTI) in the phase 3 COVERS study who were admitted to an intensive care unit (ICU).MethodsAdults with cSSTI (surface area ≥ 75 cm2) and evidence of systemic inflammation and/or underlying comorbidities were randomized 2:1 to intravenous ceftaroline fosamil (600 mg every 8 h [q8h]) or vancomycin (15 mg/kg every 12 h) plus aztreonam (1 g q8h) for 5–14 days. Clinical response and ICU length of stay (LOS) within first hospitalization were evaluated in the modified intent-to-treat (MITT) and clinically evaluable (CE) populations; a Cox proportional hazards model identified factors associated with increased hospital LOS.ResultsOverall, 42 of 761 randomized patients were admitted to the ICU (ceftaroline fosamil, n = 32; vancomycin plus aztreonam, n = 10) prior to, or at start of, study treatment. Baseline differences between the ICU and non-ICU populations were indicative of more severe disease in ICU patients; within this subset, there were also some notable imbalances between treatment groups. Clinical cure rates at test-of-cure (ceftaroline fosamil vs. vancomycin plus aztreonam) were generally similar in the non-ICU and ICU subsets (MITT population 79% vs. 79% and 69% vs. 90.0%, respectively; CE population 87% vs. 85% and 80% vs. 89%, respectively). Median ICU LOS was 8 vs. 13 days, respectively. ICU admission was a risk factor predicting increased hospital LOS (P < 0.001).ConclusionsClinical outcomes for patients admitted to the ICU were generally similar to non-ICU patients, despite more severe baseline disease, with shorter median treatment duration in the ceftaroline fosamil group. ICU admission was associated with longer hospital LOS. Given the small sample size and unbalanced patient and disease characteristics within the ICU subgroup, differences between treatment groups should be interpreted with caution.Trial registrationClinicalTrials.gov identifier, NCT01499277.Electronic supplementary materialThe online version of this article (10.1007/s40121-020-00297-3) contains supplementary material, which is available to authorized users.

Abiotrophia and Granulicatella Infections in Cancer Patients: A Single-Center Chart Review Study

Objectives: Nutritionally Variant Streptococci (NVS) comprise two primary genera that have been identified from human specimens, particularly the Abiotrophia and Granulicatella species. These infections are often complicated to manage due to the difficulty identifying these organisms, indolent course of disease, and variable resistance to common antimicrobial agents. The wide breadth of disease presentations involving these organisms has not been fully elucidated, particularly in the immunosuppressed cancer patient population. Method: We performed a retrospective chart review on 28 patients from an academic cancer center with positive NVS cultures, from January 2012 to July 2018. We reviewed patient characteristics, culture data, immunodeficiency status, response to antibiotic therapy, and outcomes of infection. Results: Of twenty-eight patients, fifteen patients developed bacteremia from either Abiotrophia or Granulicatella species, while thirteen patients had positive wound or body fluid cultures. Most patients with bacteremia had underlying hematologic malignancies and neutropenia. Patients with positive wound or body fluid cultures had an invasive procedure at the related site. Intravenous (IV) vancomycin was the most common agent used, and all but two patients were treated with multiple antibiotic regimens. Conclusions: Infections with NVS have been reported with a variety of clinically infectious presentations and should be considered in cancer patients with neutropenia or in patients who have undergone invasive procedures. Bacteremia was the most common complication, especially in the setting of hematologic malignancy and neutropenia. Focal body site infection was also a common complication related to invasive procedures in immunocompetent patients. Overall mortality was low and related to complications of septic shock. J Microbiol Infect Dis 2020; 10(2):89-97.