The Addition of Intravenous Metronidazole to Oral Vancomycin is Associated With Improved Mortality in Critically Ill Patients With Clostridium difficile Infection.

BACKGROUND: The optimal therapy for critically ill patients with Clostridium difficile infection (CDI) is not known. We aimed to evaluate mortality among critically ill patients with CDI who received oral vancomycin (monotherapy) vs oral vancomycin with intravenous (IV) metronidazole (combination therapy). METHODS: A single-center, retrospective, observational, comparative study was performed. Patients with a positive C. difficile assay who received oral vancomycin while bedded in an intensive care unit (ICU) between June 2007 and September 2012 were evaluated. Patients meeting ≥3 of the following criteria were included: albumin <2.5 g/dL, heart rate >90 bpm, mean arterial pressure <60 mmHg, white blood cell count ≥15 000 cells/mL, age >60 years, serum creatinine ≥1.5 times baseline, or temperature ≥100.4°F. Patients in the combination therapy group received IV metronidazole within 48 hours after initiating vancomycin. Patients <18 years or with unrelated gastrointestinal disease were excluded. The primary outcome was in-hospital mortality. Patients were matched using Acute Physiology and Chronic Health Evaluation II scores. RESULTS: Eighty-eight patients were included, 44 in each group. Patient characteristics were similar although more patients in the combination group had renal disease. Mortality was 36.4% and 15.9% in the monotherapy and combination therapy groups, respectively (P = .03). Secondary outcomes of clinical success, length of stay, and length of ICU stay did not differ between groups. CONCLUSIONS: Our data are supportive of the use of combination therapy with oral vancomycin and IV metronidazole in critically ill patients with CDI. However, prospective, randomized studies are required to define optimal treatment regimens in this limited population of CDI patients.

Morbidity and mortality of Serratia marcescens bacteraemia during the substance use epidemic.

BACKGROUND: Serratia marcescens (S. marcescens) is an Enterobacterales species present throughout the environment and causes a range of infections. Historically, S. marcescens has been associated with persons who inject drugs (PWID), but literature is scarce. This study aimed to compare treatment characteristics and clinical outcomes between PWID and non-PWID with Serratia marcescens bacteraemia. METHODS: This was a retrospective cohort study of patients hospitalised with S. marcescens bacteraemia from 1 January 2013 to 31 December 2019 at a tertiary medical centre. Patients were included if they were aged ≥ 18 years and had at least one positive blood culture for S. marcescens. RESULTS: Of the 67 patients who met inclusion criteria, 14 were identified as PWID (21%) and 53 were non-PWID (79%). Persons who inject drugs were younger (median age: PWID 32 years, non-PWID 67 years) and less likely to have renal disease (PWID 7%, non-PWID 34%). Persons who inject drugs had a higher incidence of infective endocarditis (IE) (PWID 48%, non-PWID 0%) and were more likely to receive combination antimicrobial therapy (PWID 29%, non-PWID 2%). All-cause mortality at 12 months was comparable between groups (PWID 21%, non-PWID 21%). CONCLUSION: This study demonstrates that long-term outcomes of PWID are comparable with non-PWID, despite PWID being a younger cohort with fewer comorbidities. Clinicians should have high suspicion of IE in PWID with S. marcescens bacteraemia.

Uncomplicated Streptococcal Bacteremia: The Era of Oral Antibiotic Step-down Therapy?

BACKGROUND: The purpose of this study was to compare the clinical outcomes of adults with uncomplicated streptococcal bacteremia who received either oral (PO) step-down or continued intravenous (IV) therapy. METHODS: This was a retrospective, single-center, cohort study, including adults admitted with Streptococcal bloodstream infection between January 1, 2013, and December 31, 2020. Only patients with uncomplicated Streptococcal bloodstream infections were included. Patients who transitioned to PO therapy within 5 days from bacteremia onset were compared to patients receiving continued IV therapy. The primary outcome was clinical failure, defined by either 90-day hospital readmission or mortality. Secondary outcomes included hospital length of stay (LOS) and antibiotic-related adverse events (AAEs). RESULTS: Of the 264 patients included, 42% were transitioned to PO therapy. Group B Streptococcus (22.7%) was the most common isolate. The most common sources of infection were skin and soft tissue (35%) and pulmonary (25%). Intensive care unit (ICU) stay was more common in the continued IV therapy group (22.2%) than in the PO step-down group (5.4%). The frequency of clinical failure was similar in the IV and PO groups (24.2% vs. 18.0%, P=0.23). The IV group had longer hospital LOS (median, [interquartile range (IQR)]) compared with the PO group (7 [5-13.5] vs. 4 [3-5] days, P<0.001). The incidence of AAEs was similar in the IV and PO groups (1.3% vs. 1.8%, P=0.74). CONCLUSION: Oral antibiotic step-down therapy may be appropriate for the treatment of uncomplicated Streptococcal bacteremia, with consideration of factors such as patient comorbidities, type of infection, source control and clinical progress.

Role of raltegravir in HIV-1 management.

OBJECTIVE: To review the literature concerning the role of raltegravir in the treatment of HIV-1 in antiretroviral (ARV)-experienced and ARV-naïve patients. DATA SOURCES: A PubMed search was conducted for published data through March 2012 using the search terms raltegravir, MK-0518, and integrase strand transfer inhibitor. An additional search of International Pharmaceutical Abstracts for unpublished data, including data from the Infectious Diseases Society of America, the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society, and the Interscience Conference on Antimicrobial Agents and Chemotherapy, was conducted using similar search terms. STUDY SELECTION AND DATA EXTRACTION: In vitro and in vivo Phase 2, Phase 3, and postmarketing studies available in English, evaluating antiretroviral regimens that contain raltegravir for the treatment of HIV-1 infection in both ARV-naïve and ARV-experienced patients, were evaluated. Studies assessing raltegravir pharmacokinetics and pharmacodynamics were included for review. DATA SYNTHESIS: The nucleoside-based regimen of raltegravir with tenofovir/emtricitabine provides an effective first-line treatment option. However, nucleoside-sparing regimens appear unfavorable in ARV-naïve subjects and should be reserved for patients with limited treatment options. Raltegravir used with optimized background therapy provides an alternative regimen for ARV-experienced patients. This review describes the available in vitro and in vivo data on raltegravir potency, defined as the ability to achieve undetectable viral load, and safety profile, as well as comparison to standard HIV-1 therapies. CONCLUSIONS: Raltegravir has demonstrated potent antiretroviral activity against HIV-1 in both ARV-naïve and ARV-experienced subjects, with the benefits of a favorable adverse effect profile and minimal drug interactions. Raltegravir must be dosed twice daily, as once daily raltegravir displays decreased virologic efficacy compared to twice daily dosing. However, the ongoing development of new integrase strand transfer inhibitors may provide potent once daily regimens.

Update on raltegravir and the development of new integrase strand transfer inhibitors.

Raltegravir (RAL) is the first antiretroviral in the integrase strand transfer inhibitors (INSTI) class. The use of RAL has expanded since its approval in October 2007 for multidrug-resistant human immunodeficiency virus type 1 infection in adults. RAL is now a guideline-preferred treatment option for antiretroviral-naïve patients, indicated for treatment in adolescents, and is being studied as an integral part of nucleoside sparing regimens. The development of resistance and the need for a once-daily dosing option has led to the development of new INSTIs, including elvitegravir and dolutegravir. Elvitegravir is being studied in a promising once-daily single-tablet regimen with tenofovir, emtricitabine, and the investigational pharmacoenhancer cobicistat. The development of cobicistat and the new once-daily INSTIs may revolutionize the treatment of human immunodeficiency virus type 1 infection. This article reviews the current literature on raltegravir and new developments in the INSTI class.

Candida Infective Endocarditis During the Infectious Diseases and Substance Use Disorder Syndemic: A Six-Year Case Series.

Treatment for Candida infective endocarditis (IE) has not been extensively studied in the setting of rising injection drug use. There were 12 cases of Candida IE at the Maine Medical Center between 2013 and 2018. The patient characteristics, treatment regimens, and outcomes were retrospectively analyzed.

Limited Clinical Utility of Follow-up Blood Cultures in Patients With Streptococcal Bacteremia: An Opportunity for Blood Culture Stewardship.

BACKGROUND: The value of positive follow-up blood cultures (FUBCs) in streptococcal bacteremia has not been well defined. Therefore, we explored the frequency of and risk factors for positive FUBC in a retrospective cohort of patients with streptococcal bacteremia. METHODS: Adults ≥18 years of age, admitted with at least 1 positive blood culture for Streptococcus spp between 2013 and 2018 followed by at least 1 FUBC, were potentially eligible. Positive FUBCs were defined as cultures positive for the same streptococcal species drawn >24 hours after the index culture. We excluded patients with polymicrobial bacteremia. We compared the characteristics of patients with and without a positive FUBC. RESULTS: In our single-center cohort, we identified 590 patients with streptococcal bacteremia, and 314 patients met inclusion criteria. Ten patients had FUBC with Streptococcus spp (3.2%), 4 (1.3%) had a contaminant identified, and 3 (1.0%) had a new pathogen isolated. Endocarditis (5 of 10 [50.0%] vs 35 of 304 [11.5%]), epidural abscess (2 of 10 [20%] vs 4 of 304 [1.3%]), and discitis or vertebral osteomyelitis (3 of 10 [30.0%] vs 14 of 304 [4.6%]) were associated with positive FUBC. Patients with positive FUBC had a longer median length of stay (12.9 vs 7.1 days, P = .004) and longer duration of antibiotic treatment (14.9 vs 43.2 days, P = .03). CONCLUSIONS: Follow-up blood cultures among patients with streptococcal BSI are rarely positive. Clinicians could consider limiting follow-up blood cultures in patients at low risk for deep-seated streptococcal infections, persistent bacteremia, or endovascular infection.

Mortality, morbidity, and cardiac surgery in Injection Drug Use (IDU)-associated versus non-IDU infective endocarditis: The need to expand substance use disorder treatment and harm reduction services.

BACKGROUND: The addiction crisis is widespread, and unsafe injection practices among people who inject drugs (PWID) can lead to infective endocarditis. METHODS: A retrospective analysis of adult patients with definite or possible infective endocarditis admitted to a tertiary care center in Portland, Maine was performed over three-year period. Our primary objective was to examine differences in demographics, health characteristics, and health service utilization between injection drug use (IDU)-associated infective endocarditis and non-IDU infective endocarditis. The association between IDU and mortality, morbidity (defined as emergency department visits within 3 months of discharge), and cardiac surgery was examined. Bivariate and multivariate analyses were performed. A subgroup descriptive analysis of PWID was also performed to better examine substance use disorder (SUD) characteristics, treatment with medication for opioid use disorder (MOUD) and health service utilization. RESULTS: One-hundred and seven patients were included in the study, of which 39.2% (n = 42) had IDU-associated infective endocarditis. PWID were more likely to be homeless, uninsured, and lack a primary care provider. PWID were notably younger and had less documented comorbidities, however had similar in-hospital mortality rates (10% vs. 14%, p = 0.30), ED visits (50% vs. 54%, p = 0.70) and cardiac surgery (33% vs. 26%, p = 0.42) compared to those with non-IDU infective endocarditis. Ninety-day mortality was less among PWID (19.0% vs. 36.9%, p = 0.05). IDU was not associated with morbidity (adjusted odds ratio (AOR) 0.73, 95% CI 0.18-3.36), 90-day mortality (AOR 0.72, 95% CI 0.17-3.01), or cardiac surgery (AOR 0.15, 95% CI 0.03-0.69). Ninety-day mortality among PWID who received MOUD was lower (3% vs 15%, p = 0.45), as were ED visits (10% vs. 41%, p = 0.42) compared to those who did not receive MOUD. CONCLUSIONS: Our results highlight existing differences in health characteristics and social determinants of health in people with IDU-associated versus non-IDU infective endocarditis. PWID had less comorbidities and were significantly younger than those with non-IDU infective endocarditis and yet still had similar rates of cardiac surgery, ED visits, and in-hospital mortality. These findings emphasize the need to deliver comprehensive health services, particularly MOUD and other harm reduction services, to this marginalized population.

Stability and compatibility of antimicrobial lock solutions.

PURPOSE: Published stability and compatibility data on a growing array of solutions used for antimicrobial lock therapy (ALT) are reviewed. SUMMARY: ALT involves the instillation of a highly concentrated antimicrobial, often in combination with an anticoagulant, into a central venous catheter (CVC) lumen; this technique is often used for prophylaxis after CVC insertion or as an adjunctive treatment in cases of central line-associated bloodstream infection (CLABSI) if catheter removal is not feasible. Optimal selection of stable and compatible antimicrobials and additives can maximize catheter dwell times, streamline pharmacy compounding practices, and help ensure patient safety. Of 98 articles on ALT solutions identified in a literature search, 17 met the prespecified criteria for the use of validated stability and compatibility methodology. Antimicrobials active against common CLABSI pathogens that may be appropriate for ALT include cefazolin, cefotaxime, ceftazidime, ciprofloxacin, daptomycin, gentamicin, linezolid, telavancin, ticarcillin-clavulanic acid, and vancomycin; validated data demonstrate the stability of these agents in solution with heparin or nonheparin anticoagulants over 72-96 hours or longer. Other antifungal agents and antiinfectives (e.g., ethyl alcohol) have been used in specific patients and ALT situations. The prolonged stability of several antimicrobial-additive combinations may allow for extended dwell times and less frequent lock solution exchanges. CONCLUSION: Pharmacists' knowledge of diverse combinations of antimicrobial agents and additives in lock solutions, including several shown to be stable and compatible for extended periods, can help expand and optimize the use of ALT in both treatment and prophylactic modalities.