Hospital-Acquired Bloodstream Infections in Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 Infection (Coronavirus Disease 2019): Association With Immunosuppressive Therapies.

BACKGROUND: Immunosuppressive therapies proposed for Coronavirus disease 2019 (COVID-19) management may predispose to secondary infections. We evaluated the association of immunosuppressive therapies with bloodstream-infections (BSIs) in hospitalized COVID-19 patients. METHODS: This was an institutional review board-approved retrospective, multicenter, cohort study of adults hospitalized with COVID-19 over a 5-month period. We obtained clinical, microbiologic and laboratory data from electronic medical records. Propensity-score-matching helped create balanced exposure groups. Demographic characteristics were compared across outcome groups (BSI/no BSI) using two-sample t-test and Chi-Square test for continuous and categorical variables respectively, while immunosuppressive therapy use was compared using McNemar's test. Conditional logistic regression helped assess the association between immunosuppressive therapies and BSIs. RESULTS: 13,007 patients were originally included, with propensity-score-matching producing a sample of 6,520 patients. 3.74% and 3.97% were diagnosed with clinically significant BSIs in the original and propensity-score-matched populations respectively. COVID-19 patients with BSIs had significantly longer hospitalizations, higher intensive care unit admission and mortality rates compared to those without BSIs. On univariable analysis, combinations of corticosteroids/anakinra [odds-ratio (OR) 2.00, 95% confidence intervals (C.I.) 1.05-3.80, P value.0342] and corticosteroids/tocilizumab [OR 2.13, 95% C.I. 1.16-3.94, P value .0155] were significantly associated with BSIs. On multivariable analysis (adjusting for confounders), combination corticosteroids/tocilizumab were significantly associated with any BSI [OR 1.97, 95% C.I. 1.04-3.73, P value.0386] and with bacterial BSIs [OR 2.13, 95% C.I. 1.12-4.05, p-value 0.0217]. CONCLUSIONS: Combination immunosuppressive therapies were significantly associated with BSI occurrence in COVID-19 patients; their use warrants increased BSI surveillance. Further studies are needed to establish their causative role.

Risk of Nephrotoxicity Associated With Nonrenally Adjusted Intravenous Polymyxin B Compared to Traditional Dosing.

BACKGROUND: Polymyxin B's package insert recommends renal adjustment. Contemporary studies suggest it does not require renal adjustment. OBJECTIVE: To determine whether time to acute kidney injury (AKI) differs between renally adjusted and nonadjusted intravenous (IV) polymyxin B. METHODS: This retrospective chart review compared time to AKI after renally adjusted and nonadjusted IV polymyxin B administration. It included patients who were 18 years or older, received IV polymyxin B, and had creatinine clearance below 80 mL/min, and excluded ones who had AKI, received renal replacement therapy, or were pregnant. RESULTS: Fifty-four patients were included. There was not any statistical association between dosing type and time to AKI (P = .13). Incidence of nephrotoxicity, mortality, and length of stay (LOS) were higher in the renally adjusted arm (21.7% vs 6.5%, 17.4% vs 6.5%, and 16 vs 14 days, respectively). Four patients received concomitant ascorbic acid; not one developed AKI. CONCLUSION: A significant association between IV polymyxin B dosing type and time to AKI was not found. Adverse events were higher in the renally adjusted arm. This suggests that nonadjusted IV polymyxin B may be preferred in patients with renal impairment. Ascorbic acid may mitigate IV polymyxin B's nephrotoxic potential. Further studies are needed to corroborate these findings.

Antimicrobial Resistant Streptococcus pneumoniae: Prevalence, Mechanisms, and Clinical Implications.

BACKGROUND: Streptococcus pneumoniae is a major cause of pneumonia, meningitis, sepsis, bacteremia, and otitis media. S. pneumoniae has developed increased resistance to multiple classes of antibiotics. STUDY DESIGN: Systematic literature review of prevalence, mechanisms, and clinical implications in S. pneumoniae resistance. AREAS OF UNCERTAINTY: Since S. pneumoniae resistance to penicillin was first reported with subsequent development of resistance to other classes of drugs, selection of appropriate antibiotic treatment is challenging. DATA SOURCES: We searched PubMed (English language) for citations to antibiotic resistance in S. pneumoniae published before March 1, 2016. RESULTS: We present a review of S. pneumoniae resistance to beta-lactams, macrolides, lincosamides, fluoroquinolones, tetracyclines, and trimethoprim-sulfamethoxazole (TMP-SMX). There has been a steady decline in susceptibility of S. pneumoniae to commonly used beta-lactams. Phenotypic expression of penicillin resistance occurs as a result of a genetic structural modification in penicillin-binding proteins. Between 20% and 40% of S. pneumoniae isolates are resistant to macrolides. Macrolide resistance mechanisms include ribosomal target site alteration, alteration in antibiotic transport, and modification of the antibiotic. Approximately 22% of S. pneumoniae isolates are resistant to clindamycin. Similar to macrolide resistance, clindamycin involves a target site alteration. The prevalence of fluoroquinolone resistance is low, although increasing. S. pneumoniae resistance to fluoroquinolones occurs by accumulated mutations within the bacterial genome, increased efflux, or acquisition of plasmid-encoded genes. S. pneumoniae resistance has also increased for the tetracyclines. The primary mechanism is mediated by 2 genes that confer ribosomal protection. The prevalence of TMP-SMX resistance is around 35%. As with fluoroquinolones, resistance to TMP-SMX is secondary to mutations in the bacterial genome. CONCLUSIONS: Effective treatment of resistant S. pneumoniae is a growing concern. New classes of drugs, newer formulations of older drugs, combination antibiotic therapy, nonantibiotic modalities, better oversight of antibiotic usage, and enhanced preventive measures hold promise.

Infections in alcoholic liver disease.

Alcoholic individuals are at increased risk of infection in general, in part because of immune defects. In addition, associated situations, such as depressed mental status, increase risk to specific syndromes such as lung abscess related to depressed consciousness and aspiration. Social factors related to hygiene and living situations are also linked to specific microorganisms, such as Mycobacteria tuberculosis, Bartonella quintana, Vibrio vulnificus, and Capnocytophaga canimorus..

Daptomycin-induced eosinophilia without pulmonary involvement.

PURPOSE: The case of a patient who developed peripheral eosinophilia associated with the use of daptomycin is described. SUMMARY: A 63-year-old man with a history of rheumatic fever during childhood arrived at the emergency department with a chief complaint of left knee pain and swelling. One week before his arrival, the patient received a corticosteroid injection for worsening pain, with minimal relief. The patient's medical history also included type 2 diabetes mellitus, hypertension, coronary artery disease, and hypercholesterolemia. The patient had a documented allergy to cephalexin (skin rash). His initial white blood cell (WBC) count was 16,500 cells/mm(3) (normal, 4,000-10,600 cells/mm(3)), with 89% neutrophils (normal, 40-80%), 5.6% lymphocytes (normal,15-45%), and 0% eosinophils (normal, 0-6%). On hospital day 2, blood cultures and aspiration cultures from the patient's knee were positive for methicillin-sensitive Staphylococcus aureus. Nafcillin and gentamicin were initiated, but on hospital day 7 the patient developed a diffuse, pruritic, macular rash believed to be secondary to nafcillin. At this point, nafcillin treatment was discontinued and daptomycin was initiated. Six days into his treatment, a routine complete blood count revealed a WBC count of 7,620 cells/mm(3), with 11.8% eosinophils. The eosinophils continued to increase, peaking at 34.1% after 26 days of treatment with daptomycin. After cessation of daptomycin, the peripheral eosinophilia resolved. At no point during his hospitalization did the patient have evidence of pulmonary involvement. CONCLUSION: A 63-year-old man developed peripheral eosinophilia without evidence of pulmonary involvement while being treated with daptomycin.

Neurotoxicity in patients treated with intravenous polymyxin B: Two case reports.

PURPOSE: Two cases of reversible neurotoxicity associated with the administration of intravenous polymyxin B are described. SUMMARY: In the first case, a 60-year-old, obese, white woman with a medical history of recurring urinary tract infections, nephrolithiasis, and chronic renal insufficiency was admitted for parenteral antibiotics for dysuria and hematuria despite outpatient management with oral antibiotics. Her urinalysis revealed pyuria and large blood content. The corresponding urine culture contained >or=100,000 colony-forming units/mL of multidrug-resistant (MDR) Klebsiella pneumoniae. The patient was treated with polymyxin B at 20,000 units/kg i.v. as a loading dose and then 10,000 units/kg i.v. daily based on her renal function. The patient experienced oral paresthesia that resolved upon discontinuation of the infusion with no further complications. In the second case, a 57-year-old white man with hypertension and ascending cholangitis was admitted. He required percutaneous drainage of an infected pancreatic cyst and received polymyxin B at 25,000 units/kg i.v. as a loading dose and then 15,000 units/kg i.v. daily in addition to imipenem-cilastatin based on the sensitivities of two organisms (Escherichia coli and MDR K. pneumoniae) isolated from the abdominal drainage. For his pancreatic abscess, the patient received a prolonged course of polymyxin B, which was well tolerated for the first four weeks. On day 30 of the polymyxin B, the patient reported oral and lower extremity paresthesias. The symptoms resolved upon discontinuation of the polymyxin B. CONCLUSION: Two patients developed symptoms of neurotoxicity after receiving intravenous polymyxin B for the treatment of MDR gram-negative infections.

Tigecycline: a glycylcycline antimicrobial agent.

BACKGROUND: Tigecycline, the first glycylcycline to be approved by the US Food and Drug Administration, is a structural analogue of minocycline that was designed to avoid tetracycline resistance mediated by ribosomal protection and drug efflux. It is indicated for the treatment of complicated skin and skin-structure infections and complicated intra-abdominal infections and is available for intravenous administration only. OBJECTIVE: This article summarizes the in vitro and in vivo activities and pharmacologic and pharmacokinetic properties of tigecycline, and reviews its clinical efficacy and tolerability profile. METHODS: Relevant information was identified through a search of MEDLINE (1966-April 2006), Iowa Drug Information Service (1966-April 2006), and International Pharmaceutical Abstracts (1970-April 2006) using the terms tigecycline, GAR-936, and glycylcycline. Also consulted were abstracts and posters from meetings of the Infectious Diseases Society of America and the Interscience Conference on Antimicrobial Agents and Chemotherapy (1999-2006) and documents provided for formulary consideration by the US manufacturer of tigecycline. RESULTS: Like the tetracyclines, tigecycline binds to the 30S subunit of bacterial ribosomes and inhibits protein synthesis by preventing the incorporation of amino acid residues into elongating peptide chains. In vitro, tigecycline exhibits activity against a wide range of clinically significant gram-positive and gram-negative bacteria, including multidrug-resistant strains (eg, oxacillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Enterobacteriaceae), and anaerobes (eg, Bacteroides spp). In pharmacokinetic studies in human adults, tigecycline had a large Vd (7-9 L/kg), was moderately bound to plasma protein (71%-89%), had an elimination t(1/2) of 42.4 hours, and was eliminated primarily by biliary/fecal (59%) and renal (33%) excretion. Dose adjustment did not appear to be necessary based on age, sex, renal function, or mild to moderate hepatic impairment (Child-Pugh class A-B). In patients with severe hepatic impairment (Child-Pugh class C), the maintenance dose should be reduced by 50%. In 4 Phase III clinical trials in patients with complicated skin and skin-structure infections and complicated intra-abdominal infections, tigecycline was reported to be noninferior to its comparators (vancomycin + aztreonam in 2 studies and imipenem/cilastatin in 2 studies), with clinical cure rates among clinically evaluable patients of >80% (P < 0.001 for noninferiority). The most frequently reported (> or =5 %) adverse events with tigecycline were nausea (28.5%), vomiting (19.4%), diarrhea (11.6%), local IV-site reaction (8.2%), infection (6.7%), fever (6.3%), abdominal pain (6.0%), and headache (5.6%). The recommended dosage of tigecycline is 100 mg IV given as a loading dose, followed by 50 mg IV g12h for 5 to 14 days. CONCLUSIONS: In clinical trials, tigecycline was effective for the treatment of complicated skin and skin-structure infections and complicated intra-abdominal infections. With the exception of gastrointestinal adverse events, tigecycline was generally well tolerated. With a broad spectrum of activity that includes multidrug-resistant gram-positive and gram-negative pathogens, tigecycline may be useful in the treatment of conditions caused by these pathogens.

Tinidazole: a nitroimidazole antiprotozoal agent.

BACKGROUND: Tinidazole, a structural analogue of metrondazole, is an antiprotozoal agent that has been widely used in Europe and developing countries for >2 decades with established efficacy and acceptable tolerability. It was recently approved by the US Food and Drug Administration for the treatment of trichomoniasis, giardiasis, amebiasis, and amebic liver abscess. OBJECTIVE: This article reviews the pharmacologic and pharmacokinetic properties and clinical usefulness of tinidazole. METHODS: Relevant information was identified through a search of MEDLINE (1966-August 2005), Iowa Drug Information Service (1966-August 2005), and International Pharmaceutical Abstracts (1970-August 2005) using the terms tinidazole, Fasigyn, and nitroimidazole. RESULTS: In vitro, tinidazole exhibits activity against pathogenic protozoa (eg, Tricbomonas vaginalis, Entamoeba bistolytica, Giardia duodenalis), a wide range of clinically significant anaerobic bacteria (eg, Bacteroides fragilis, Clostridium difficile), and the microaerophilic bacterium Helicobacter pylori. In susceptible protozoal and bacterial cells, tinidazole is reduced to cytotoxic intermediates that covalently bind to DNA, causing irreversible damage. In human adults, tinidazole had a bioavailability of 100% and a V(d) of 50.7 L, was minimally bound to plasma protein (12%), had a plasma elimination t((1/2)) of 12.3 hours, and was eliminated primarily by hepatic metabolism (approximately 63%). Dose adjustment does not appear to be necessary on the basis of race, sex, or renal function. No data were found on the disposition of tinidazole in patients with hepatic insufficiency; therefore, use of tinidazole in patients with severe hepatic impairment (Child-Pugh class C) is not recommended. Clinical cure rates in patients with trichomoniasis, giardiasis, amebiasis, and amebic liver abscess were generally >90%. In comparative trials, tinidazole was as effective as metronidazole in the treatment of trichomoniasis and was significantly more effective than metronidazole in the treatment of giardiasis (P < 0.05) and amebiasis (P < 0.05). The most commonly reported (>1%) adverse effects included bitter taste, nausea, abdominal discomfort, anorexia, vomiting, and fatigue. The recommended dosage of tinidazole is a single dose of 2 g for trichomoniasis and giardiasis, and 2 g/d for 3 to 5 days for amebiasis. CONCLUSIONS: Tinidazole appears to be a promising agent for the treatment of trichomoniasis, giardiasis, amebiasis, and amebic liver abscess. Clinical studies are needed to evaluate the use of tinidazole against anaerobic bacteria and H pylori.