Rethinking Carbapenems: A Pharmacokinetic Approach for Antimicrobial Selection in Infected Necrotizing Pancreatitis.

OBJECTIVE: To provide an overview of pathophysiological changes to the pancreas during infected necrotizing pancreatitis (INP), optimal drug properties needed to penetrate the pancreas, human and animal studies supporting the use of antimicrobials, and carbapenem-sparing strategies in INP. DATA SOURCES: A literature analysis of PubMed/MEDLINE was performed (from 1960 to September 2020) using the following key terms: infected necrotizing pancreatitis, necrotizing acute pancreatitis, and infected pancreatitis antimicrobial concentration. Individual antimicrobials were investigated with these search terms. STUDY SELECTION AND DATA EXTRACTION: All relevant studies describing the management of INP, and human and animal pharmacokinetic (PK) data supporting antimicrobial use in the pancreas were reviewed for possible inclusion regardless of sample size or study design. DATA SYNTHESIS: Piperacillin/tazobactam and cefepime achieve adequate pancreatic tissue concentrations in INP studies. A majority of the literature supporting carbapenem use in INP involves imipenem, and meropenem Monte Carlo simulations suggest that standard dosing regimens of meropenem may not achieve PK targets to eradicate Pseudomonas aeruginosa. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Carbapenems are often utilized for INP treatment based on guideline recommendations. This review discusses PK data, the history of carbapenem use in INP, and the pathophysiology of pancreatitis to suggest carbapenem-sparing strategies and provides stewardship tactics such as when to start antimicrobials, which empirical antimicrobial to use, and when to discontinue antimicrobials in the INP setting. CONCLUSIONS: Noncarbapenem antipseudomonals, such as piperacillin/tazobactam and cefepime, are appropriate carbapenem-sparing options in INP, based on PK data, spectrum of activity, and risk of collateral damage.

Seasonal variation of macrolide resistance gene abundances in the South Fork Iowa River Watershed.

The Midwestern United States is dominated by agricultural production with high concentrations of swine, leading to application of swine manure onto lands with artificial subsurface drainage. Previous reports have indicated elevated levels of antibiotic resistance genes (ARGs) in surface water and groundwater around confined animal feeding operations which administer antimicrobials. While previous studies have examined the occurrence of ARGs around confined swine feeding operations, little information is known how their transport from tile-drained fields receiving swine manure application impacts downstream environments. To further our knowledge in this area, water samples were collected from five locations in the agriculturally dominated South Fork Iowa River Watershed with approximately 840,000 swine present in the 76,000ha basin. Samples were collected monthly from three stream sites and two main artificial subsurface drainage outlets. Samples were analyzed for macrolide resistance genes ermB, ermF and 16S rRNAgene abundance using qPCR. Abundance of erm genes ranged from below limits of quantification to >107 copies 100mL-1 water. Eighty-nine percent of stream water samples contained one of these two ARGs. Results indicate significantly more ermB and ermF in main drainage outlets than stream samples when normalized by 16S rRNA abundance (p<0.0001). Both artificial drainage locations revealed temporal trends for ermB and ermF abundance when normalized to 16S rRNA abundance. The higher resistance gene concentrations identified in artificial drainage samples occurring mid-Spring and late-Fall are likely due to manure application.

Effect of a Health Care System Respiratory Fluoroquinolone Restriction Program To Alter Utilization and Impact Rates of Clostridium difficile Infection.

Fluoroquinolones are one of the most commonly prescribed antibiotic classes in the United States despite their association with adverse consequences, including Clostridium difficile infection (CDI). We sought to evaluate the impact of a health care system antimicrobial stewardship-initiated respiratory fluoroquinolone restriction program on utilization, appropriateness of quinolone-based therapy based on institutional guidelines, and CDI rates. After implementation, respiratory fluoroquinolone utilization decreased from a monthly mean and standard deviation (SD) of 41.0 (SD = 4.4) days of therapy (DOT) per 1,000 patient days (PD) preintervention to 21.5 (SD = 6.4) DOT/1,000 PD and 4.8 (SD = 3.6) DOT/1,000 PD posteducation and postrestriction, respectively. Using segmented regression analysis, both education (14.5 DOT/1,000 PD per month decrease; P = 0.023) and restriction (24.5 DOT/1,000 PD per month decrease; P < 0.0001) were associated with decreased utilization. In addition, the CDI rates decreased significantly (P = 0.044) from preintervention using education (3.43 cases/10,000 PD) and restriction (2.2 cases/10,000 PD). Mean monthly CDI cases/10,000 PD decreased from 4.0 (SD = 2.1) preintervention to 2.2 (SD = 1.35) postrestriction. A significant increase in appropriate respiratory fluoroquinolone use occurred postrestriction versus preintervention in patients administered at least one dose (74/130 [57%] versus 74/232 [32%]; P < 0.001), as well as in those receiving two or more doses (47/65 [72%] versus 67/191 [35%]; P < 0.001). A significant reduction in the annual acquisition cost of moxifloxacin, the formulary respiratory fluoroquinolone, was observed postrestriction compared to preintervention within the health care system ($123,882 versus $12,273; P = 0.002). Implementation of a stewardship-initiated respiratory fluoroquinolone restriction program can increase appropriate use while reducing overall utilization, acquisition cost, and CDI rates within a health care system.

Group A streptococcal toxic shock syndrome secondary to necrotizing pelvic inflammatory disease in a postmenopausal woman.

Group A ß-hemolytic streptococcus (GAS) is well known to cause upper respiratory tract or cutaneous infections, but some more virulent species of GAS can lead to a rapidly progressive life threatening soft tissue necrotizing infection and streptococcal toxic shock syndrome (STSS). In the modern era, GAS infections within the female reproductive tract leading to STSS are unusual and are often the result of retained products of conception or intrauterine devices. This report describes a case of GAS necrotizing pelvic infection in a previously healthy menopausal woman with no obvious portal of entry. Her clinical course rapidly progressed to septic shock and multiorgan failure. She required multiple surgeries in addition to targeted antimicrobials and aggressive management of shock and organ failures. After a prolonged hospital stay, she had a full recovery.

Fukushima-derived radionuclides in the ocean and biota off Japan.

The Tohoku earthquake and tsunami of March 11, 2011, resulted in unprecedented radioactivity releases from the Fukushima Dai-ichi nuclear power plants to the Northwest Pacific Ocean. Results are presented here from an international study of radionuclide contaminants in surface and subsurface waters, as well as in zooplankton and fish, off Japan in June 2011. A major finding is detection of Fukushima-derived (134)Cs and (137)Cs throughout waters 30-600 km offshore, with the highest activities associated with near-shore eddies and the Kuroshio Current acting as a southern boundary for transport. Fukushima-derived Cs isotopes were also detected in zooplankton and mesopelagic fish, and unique to this study we also find (110 m)Ag in zooplankton. Vertical profiles are used to calculate a total inventory of ~2 PBq (137)Cs in an ocean area of 150,000 km(2). Our results can only be understood in the context of our drifter data and an oceanographic model that shows rapid advection of contaminants further out in the Pacific. Importantly, our data are consistent with higher estimates of the magnitude of Fukushima fallout and direct releases [Stohl et al. (2011) Atmos Chem Phys Discuss 11:28319-28394; Bailly du Bois et al. (2011) J Environ Radioact, 10.1016/j.jenvrad.2011.11.015]. We address risks to public health and marine biota by showing that though Cs isotopes are elevated 10-1,000× over prior levels in waters off Japan, radiation risks due to these radionuclides are below those generally considered harmful to marine animals and human consumers, and even below those from naturally occurring radionuclides.

Tricuspid valve gonococcal endocarditis: fourth case report.

Disseminated gonococcal infection (DGI) occurs in 1-3% of all gonococcal infections; endocarditis is a complication in 1-2% of patients with DGI. We present the fourth reported case of gonococcal tricuspid valve endocarditis, this one occurring in a 53-year-old male with a 2-month history of shortness of breath.