Background Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) management remains challenging for clinicians. Numerous in vitro studies report synergy when vancomycin (VAN)/daptomycin (DAP) were combined with beta-lactams (BL), which has led to clinical implementation of these combinations. While shorter durations of bacteremia have often been reported, there has been no significant impact on mortality. Methods The Detroit Medical Center (DMC) developed and implemented a clinical pathway algorithm for MRSA BSI treatment in 2016 that included the early use of BL combination therapy with standard-of-care (VAN or DAP) and a mandatory infectious diseases consultation. This was a retrospective, quasi-experimental study at the DMC between 2013-2020. Multivariable logistic regression was used to assess the independent association between pathway implementation and 30-day mortality while adjusting for confounding variables. Results Overall, 813 adult patients treated for MRSA BSI were evaluated. Compared to pre-pathway (PRE) patients (n=379), those treated post-pathway (POST) (n=434) had a significant reduction in 30-day and 90-day mortality; 9.7% in POST vs. 15.6% in PRE (p=0.011) and 12.2% in POST vs. 19.0% in PRE (p=0.007), respectively. The incidence of acute kidney injury (AKI) was higher in the PRE compared to POST; 9.6% vs. 7.2% (p=0.282), respectively. After adjusting for confounding variables including infectious diseases consult, POST was independently associated with a reduction in 30-day mortality (adjusted odds ratio [aOR], 0.608; 95% confidence interval [CI], 0.375-0.986). Conclusions Implementation of a MRSA BSI treatment pathway with early use of BL reduced mortality with no increased in AKI. Further prospective evaluation of this pathway approach is warranted.
Introduction Inappropriate antibiotic use in COVID-19 is often due to treatment of presumed bacterial coinfection. Predictive factors to distinguish COVID-19 from COVID-19 with bacterial coinfection or bloodstream infection are limited. Methods We conducted a retrospective cohort study of 595 COVID-19 patients admitted between March 8, 2020, and April 4, 2020, to describe factors associated with a bacterial bloodstream coinfection (BSI). The primary outcome was any characteristic associated with BSI in COVID-19, with secondary outcomes including 30-day mortality and days of antibiotic therapy (DOT) by antibiotic consumption (DOT/1000 patient-days). Variables of interest were compared between true BSI ( n = 25) and all other COVID-19 cases ( n = 570). A secondary comparison was performed between positive blood cultures with true BSI ( n = 25) and contaminants ( n = 33) on antibiotic use. Results Fever (> 38 °C) (as a COVID-19 symptom) was not different between true BSI ( n = 25) and all other COVID-19 patients ( n = 570) ( p = 0.93), although it was different as a reason for emergency department (ED) admission ( p = 0.01). Neurological symptoms (ED reason or COVID-19 symptom) were significantly higher in the true BSI group ( p < 0.01, p < 0.01) and were independently associated with true BSI (ED reason: OR = 3.27, p < 0.01; COVID-19 symptom: OR = 2.69, p = 0.03) on multivariate logistic regression. High (15–19.9 × 10 9 /L) white blood cell (WBC) count at admission was also higher in the true BSI group ( p < 0.01) and was independently associated with true BSI (OR = 2.56, p = 0.06) though was not statistically significant. Thirty-day mortality was higher among true BSI ( p < 0.01). Antibiotic consumption (DOT/1000 patient-days) between true BSI and contaminants was not different ( p = 0.34). True bloodstream coinfection was 4.2% (25/595) over the 28-day period. Conclusion True BSI in COVID-19 was associated with neurological symptoms and nonsignificant higher WBC, and led to overall higher 30-day mortality and worse patient outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-022-00636-6.
Stenotrophomonas maltophilia is an opportunistic pathogen and frequent cause of serious nosocomial infections. Patient populations at greatest risk for these infections include the immunocompromised and those with chronic respiratory illnesses and prior antibiotic exposure, notably to carbapenems. Its complex virulence and resistance profile drastically limit available antibiotics, and incomplete breakpoint and pharmacokinetic/pharmacodynamic (PK/PD) data to inform dose optimization further complicates therapeutic approaches. Clinical comparison data of first‐line agents, including trimethoprim‐sulfamethoxazole (TMP‐SMX), quinolones, and minocycline, are limited to conflicting observational data with no clear benefit of a single agent or combination therapy. Newer antibiotic approaches, including cefiderocol and aztreonam‐ avibactam, are promising alternatives for extensively drug‐resistant isolates; however, clinical outcomes data are needed. The potential clinical utility of bacteriophage for compassionate use in treating S. maltophilia infections remains to be determined since data is limited to in‐vitro and sparse in‐vivo work. This article provides a review of available literature for S. maltophilia infection management focused on related epidemiology, resistance mechanisms, identification, susceptibility testing, antimicrobial PK/PD, and emerging therapeutic strategies.
Introduction Reducing infection in burn patients can have a major impact on clinical outcomes. The purpose of this study is to evaluate the rate of bacteremia pre/post the implementation of a line change and nasal decolonization protocol. Methods This quasi-experimental study assessed adult patients admitted to a single center ABA verified burn center from August 2019 - August 2020 (pre-intervention group) versus September 2020 - September 2021 (post-intervention group). Patients must have received at least 1 round of intranasal decolonization treatment (mupirocin intranasal twice a day for 5 days and repeated every 30 days during hospital stay) during the post-protocol period. A line change policy was also implemented post protocol period for central and peripheral lines. Patients were excluded if they had a total loss of nasal alae, injury deemed nonsurvivable, or transitioned to comfort care within 72 hours of admission. Results A total of 558 burn patients were included, 324 patients in the pre-group and 234 post-group. There was no significant difference in comorbidities between the two groups. The majority of patients were admitted for an integumentary burn (87.6%) with the most common cause being flame (49.8%) or hot water contact (19.0%). Compliance with the decolonization protocol was appropriate for 87.6% of patients post-intervention. During the pre-intervention period, there were 18 (7.7%) positive blood cultures versus only 9 (3.8%) in the post-group (p=0.426). Gram-positive infections occurred in 44.4% of the pre-group and only 11.1% in the post-group (p=0.087). The rate of Gram-negative infections was similar between the pre and post-groups at 44.4% and 55.6%, p = 0.695. MRSA bacteremia was 44.4% of total Gram-positive bacteremia, with pre and post-intervention 4 (50%) vs. 0 (0%), p = 0.1. The median time of line placement to bacteremia pre-intervention was 7(5-12) days vs. post-intervention 11(6-14) days (p = 0.220). Hospital mortality between both periods was 9(3.8%) vs. 5(2.1%), p = 0.786. No significant difference was found in hospital LOS, ICU LOS, or discharge disposition. Conclusions Overall, this study showed a 50% decreased rate of MRSA bacteremia with the implementation of an intranasal decolonization protocol and a delay in Gram-negative bacteremia post implementation of a line change policy, potentially leading to a decrease in morbidity and hospital bloodstream infection-related costs. Applicability of Research to Practice Reducing infection rates can have a major impact on burn patient outcomes and lead to significant cost savings.
Burn patients have numerous risk factors for multidrug resistant organisms (MDROs) and altered pharmacokinetics, which both independently increase the risk of treatment failure. Data on appropriate antimicrobial dosing are limited in this population and therapeutic drug monitoring (TDM) for beta-lactams is impractical at most facilities. 1-3 Technology is available that can detect genetic markers of resistance, but they are not all encompassing, and often require specialized facilities that can detect less common genetic markers. 4-5 Newer antimicrobials can help combat MDROs, but additional resistance patterns may evolve during treatment. Considering drug shortages and antimicrobial formularies, clinicians must remain vigilant when treating infections. This case report describes the development of resistance to ceftazidime-avibactam in a burn patient. The patient was a 54- year-old burn victim with a 58% total body surface area (TBSA) thermal burn who underwent multiple courses of antibiotics for various Pseudomonal infections. The initial Pseudomonal wound infection was sensitive to cefepime, aminoglycosides, and meropenem. A subsequent resistant pseudomonal pneumonia was treated with ceftazidime-avibactam 2.5 grams every 6 hours due to the elevated MIC to cefepime (16mcg/mL) and meropenem (>8mcg/mL). Although, the patient improved over 7 days, the patient again spiked fevers and had increased white blood counts (WBC). Repeat blood cultures demonstrated a multidrug resistant (MDR) Pseudomonas with a minimum inhibitory concentration (MIC) to ceftazidime-avibactam of 16mcg/mL, which is above the Clinical and Laboratory Standards Institute (CLSI) breakpoint of 8mcg/mL. At first, resistance was thought to have occurred due to inadequate dosing, but genetic work demonstrated multiple genes encoding beta-lactamases.
Background The Drug Resistance in Pneumonia (DRIP) score is a predictive model for identifying drug-resistant pathogens in community-acquired pneumonia (CAP). The Detroit Medical Center adopted DRIP documentation at time of antimicrobial order entry for CAP in 2017. The purpose of this study was to identify the difference in overall consumption of antibiotics used for the treatment of CAP after the implementation of DRIP documentation. Methods A retrospective analysis of adult patients with an antimicrobial order with a documented indication of pneumonia between Jun 1-Oct 31, 2017 and Jun 1-Oct 31, 2018, was conducted. Days of antimicrobial therapy per 1000 adjusted patient days (DOT/1000 pt days) was assessed in patients before and after implementation of DRIP documentation at time of order entry. The percent concordance with institutional guidelines for empiric CAP treatment post-implementation of DRIP documentation was also evaluated. Results The DOT/1000 pt days increased in the post-DRIP group for ceftriaxone (36.5 vs. 76.3), doxycycline (22.3 vs. 44.5), and azithromycin (29.5 vs. 53.4). The DOT/1000 pt days decreased for carbapenems in the post-DRIP group (14.0 vs. 8.5). There was no change in vancomycin or linezolid use. Empiric therapy after implementation of DRIP documentation was concordant with institutional guidelines in 34.7% and 11.2% of patients with documented DRIP< 4 and DRIP≥4, respectively. Overall, the most common reason for non-concordance was lack of atypical coverage. Use of expanded Gram-negative coverage (i.e. cefepime) for documented DRIP< 4, and lack of expanded Gram-negative coverage with aminoglycosides in ICU patients with documented DRIP≥4 were also common Conclusion An increase in guideline-directed therapy and a decrease in use of carbapenems were seen after implementation of DRIP score documentation at time of order entry. Overall concordance with guidelines was low, and additional review is needed to identify if providers are accurately documenting the DRIP score. Future directions should focus on education of clinicians on the importance of accurate DRIP documentation in order to improve compliance with institutional guidelines. Disclosures All Authors: No reported disclosures
Background Inpatient antibiotic use early on in the COVID-19 pandemic may have increased due to the inability to distinguish between bacterial and COVID-19 pneumonia. The purpose of this study was to determine the impact of COVID-19 on antimicrobial usage during three separate waves of the COVID-19 pandemic. Methods We conducted a retrospective review of patients admitted to Detroit Medical Center between 3/10/19 to 4/24/21. Median days of therapy per 1000 adjusted patient days (DOT/1000 pt days) was evaluated for all administered antibiotics included in our pneumonia guidelines during 4 separate time periods: pre-COVID (3/3/19-4/27/19); 1st wave (3/8/20-5/2/20); 2nd wave (12/6/21-1/30/21); and 3rd wave (3/7/21-4/24/21). Antibiotics included in our pneumonia guidelines include: amoxicillin, azithromycin, aztreonam, ceftriaxone, cefepime, ciprofloxacin, doxycycline, linezolid, meropenem, moxifloxacin, piperacillin-tazobactam, tobramycin, and vancomycin. The percent change in antibiotic use between the separate time periods was also evaluated. Results An increase in antibiotics was seen during the 1st wave compared to the pre-COVID period (2639 [IQR 2339-3439] DOT/1000 pt days vs. 2432 [IQR 2291-2499] DOT/1000 pt days, p=0.08). This corresponded to an increase of 8.5% during the 1st wave. This increase did not persist during the 2nd and 3rd waves of the pandemic, and the use decreased by 8% and 16%, respectively, compared to the pre-COVID period. There was an increased use of ceftriaxone (+6.5%, p=0.23), doxycycline (+46%, p=0.13), linezolid (+61%, p=0.014), cefepime (+50%, p=0.001), and meropenem (+29%, p=0.25) during the 1st wave compared to the pre-COVID period. Linezolid (+39%, p=0.013), cefepime (+47%, p=0.08) and tobramycin (+47%, p=0.05) use remained high during the 3rd wave compared to the pre-COVID period, but the use was lower when compared to the 1st and 2nd waves. Figure 1. Antibiotic Use 01/2019 to 04/2019 Conclusion Antibiotics used to treat bacterial pneumonia during the 1st wave of the pandemic increased and there was a shift to broader spectrum agents during that period. The increased use was not sustained during the 2nd and 3rd waves of the pandemic, possibly due to the increased awareness of the differences between patients who present with COVID-19 pneumonia and bacterial pneumonia. Disclosures All Authors: No reported disclosures
Background Acinetobacter (ACB) infections are difficult to treat due to increasing drug resistance. The aim of this study is to evaluate the effectiveness of high-dose (HD) minocycline (MIN) 200mg q12h for the treatment of ACB infections Methods This is a retrospective study of pts with ACB from 1/1/19 to 10/31/20. Exclusions included non-susceptibility to MIN, age < 18 yrs, hospice care w/in 72 hrs of culture, or urine source. Use of HD MIN (IV or PO), was compared to alternative treatment (AT). Clinical and micro success at the end of therapy (EOT) was evaluated. Clinical success was elimination or improvement in signs and symptoms of infection. Micro success was eradication of ACB from the same site of infection at EOT. Length of stay (LOS), 30-day readmission (with or without ACB), isolation of a MIN non-susceptible ACB within 30 days of EOT, and adverse events related to MIN, were evaluated. Results A total of 320 pts were screened with the most common exclusion being MIN non-susceptible isolate. Of the 204 pts included, 38 received HD MIN and 166 received AT. The most common were cefepime (53/166) and meropenem (36/166). Median age (IQR) was 41 (30-50) yrs for HD MIN vs. 40 (27-48) yrs for AT. Both groups were mostly male (HD MIN: 63% vs. AT: 60%) and respiratory was the most common site (HD MIN: 61% vs. AT: 60%). HD MIN group had 74% of cultures that were polymicrobial vs. 86% in AT group. Lack of clinical response at the EOT occurred in 42% of pts on HD MIN and 37% on AT. Infection related mortality occurred in 24% on HD MIN vs. 15% on AT. In HD MIN group, 16 pts had a repeat culture from the same site after treatment with 25% still positive for ACB. In the AT group 61 pts had a repeat culture and 28% were positive for ACB. Duration of treatment (9 [6-11] days vs. 10 [2-18] days) and LOS (16 [18.25-26.75] vs. 29 [14-49]) were shorter in the HD MIN group. There was only one adverse event reported with the use of HD MIN Conclusion Pts in the HD MIN group had shorter treatment duration and a shorter LOS. Pts who received HD MIN had a lower rate of clinical cure and a higher mortality rate compared to pts in the AT group. Reasons for this difference will need to be investigated further. HD MIN should be reserved for pts who are unable to tolerate other treatment options or who have an ACB resistant to other treatment options. Disclosures All Authors: No reported disclosures
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