Outcomes of Clostridioides difficile in Patients with Vitamin D Deficiency: A Propensity-Matched National Inpatient Sample Analysis.

OBJECTIVES: We aimed to determine in-hospital outcomes, length of hospital stay, and resource utilization in a contemporary cohort of Clostridioides difficile infection (CDI) and vitamin D deficiency (VDD). METHODS: The National Inpatient Sample database for 2016 and 2017 was used for data analysis using International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System (ICD-10-CM/PCS) codes to identify the patients with the principal diagnosis of CDI and VDD. We assessed the all-cause in-hospital mortality, morbidity, length of hospital stay (LOS), and total costs between propensity-matched groups of CDI without VDD versus CDI with VDD. RESULTS: We identified 202,234 patients with CDI, 4515 of whom were patients with VDD and 197,719 of whom were without VDD. After propensity matching, there was no difference in the in-hospital mortality between the two groups (odds ratio [OR] 1.5, 95% confidence interval [CI] 0.58-4.3; P = 0.90). CDI with VDD has a higher odds of sepsis (OR 1.6, 95% CI 1.3-1.9; P = 0.0), and peritonitis (OR 1.6, 95% CI 1.4-3.8; P = 0.01). Mean LOS (5.9 ± 1.8 vs 5.4 ± 2, P < 0.01) and mean total charges ($11,500 vs $9971, P < 0.04) were higher in CDI with VDD. The factors affecting the LOS were acute coronary syndrome (P = 0.04), mechanical ventilation (P = 0.03), obesity (P = 0.004), acute kidney injury (P = 0.04), and sepsis (P = 0.05). CONCLUSIONS: In this large cohort in a propensity-matched analysis, VDD does not increase the in-hospital mortality in CDI. VDD increases the odds of complications with a higher LOS and resource utilization. These findings may be clinically relevant to guide clinicians to routinely monitor vitamin D status and supplement in patients at risk of CDI.

The association of a reduced susceptibility to moxifloxacin in causative Clostridium (Clostridioides) difficile strain with the clinical outcome of patients.

OBJECTIVES: To investigate the relationship between Clostridium (Clostridioides) difficile strain characteristics and C. difficile infection (CDI) outcome. METHODS: Between October and December 2017, 16 hospitals collected epidemiological data according to the European Centre for Disease Prevention and Control (ECDC) surveillance protocol for CDI. C. difficile isolates were characterized by ribotyping, toxin genes detection and antibiotic susceptibility testing to metronidazole, vancomycin and moxifloxacin. RESULTS: The overall mean CDI incidence density was 4.5 [95% CI 3.6-5.3] cases per 10,000 patient-days. From the 433 CDI cases, 330 (76.2%) were healthcare-associated, 52 (12.0%) cases were community-associated or of unknown origin and 51 (11.8%) CDI cases recurrent; a complicated course of CDI was reported in 65 cases (15.0%). Eighty-eight (20.3%) of patients died and 59 of them within 30 days after the CDI diagnosis. From the 379 C. difficile isolates, the most prevalent PCR ribotypes were 001 (n = 127, 33.5%) and 176 (n = 44, 11.6%). A total of 186 (49.1%) isolates showed a reduced susceptibility to moxifloxacin (> 4 mg/L) and 96.4% of them had Thr82Ile in the GyrA. Nineteen isolates revealed reduced susceptibility to metronidazole and two isolates to vancomycin (> 2 mg/L). A fatal outcome was associated with a reduced susceptibility to moxifloxacin, the advanced age of the patients and a complicated course of CDI (p<0.05). No association between ribotype, binary toxin and a reduced susceptibility to moxifloxacin and complicated course or recurrent CDI was found. CONCLUSIONS: A reduced susceptibility to moxifloxacin, in causative C. difficile strains was associated with fatal outcome of the patients, therefore it is an important marker in surveillance of CDI.

Efficacy of avilamycin for the prevention of necrotic enteritis caused by a pathogenic strain of Clostridium perfringens in broiler chickens.

The efficacy of avilamycin for the prevention of necrotic enteritis (NE) was investigated in a 35-day floor pen study of 2200 broiler cockerels using a Clostridium perfringens (Cp) feed inoculum challenge model. Treatments consisted of (1) nonmedicated, nonchallenged; (2) nonmedicated, challenged; (3) avilamycin at 15 ppm, challenged; (4) avilamycin at 30 ppm, challenged. Avilamycin was administered in the feed from day 7 to day 30 of the study. Challenge inoculum was administered on day 14 and delivered approximately 10(9) CFU Cp/bird. NE mortality rates from day 14-35 were significantly (P < 0.0001) lower in birds treated with avilamycin at 15 and 30 ppm when compared to nonmedicated, challenged birds. Treatment with avilamycin also resulted in a significant reduction in ileal Cp count on day 21 (P < 0.0001) and NE lesion scores on day 17 (P < 0.006) when compared to nonmedicated, challenged birds. The performance of birds treated with avilamycin was also improved when compared to nonmedicated, challenged birds. Cockerels that received either 15 or 30 ppm avilamycin had a significantly (P < 0.0001) increased body weight on day 35 and average daily gain from days 0-35 than nonmedicated, challenged birds. Furthermore, birds treated with avilamycin had an improved feed conversion rate from days 0-35 compared to both nonmedicated, nonchallenged birds and nonmedicated, challenged birds. This study confirms that avilamycin is effective at controlling mortality related to NE in growing broiler chickens.

In vitro and in vivo antibacterial evaluation of cadazolid, a new antibiotic for treatment of Clostridium difficile infections.

Clostridium difficile is a leading cause of health care-associated diarrhea with significant morbidity and mortality, and new options for the treatment of C. difficile-associated diarrhea (CDAD) are needed. Cadazolid is a new oxazolidinone-type antibiotic that is currently in clinical development for treatment of CDAD. Here, we report the in vitro and in vivo antibacterial evaluation of cadazolid against C. difficile. Cadazolid showed potent in vitro activity against C. difficile with a MIC range of 0.125 to 0.5 µg/ml, including strains resistant to linezolid and fluoroquinolones. In time-kill kinetics experiments, cadazolid showed a bactericidal effect against C. difficile isolates, with >99.9% killing in 24 h, and was more bactericidal than vancomycin. In contrast to metronidazole and vancomycin, cadazolid strongly inhibited de novo toxin A and B formation in stationary-phase cultures of toxigenic C. difficile. Cadazolid also inhibited C. difficile spore formation substantially at growth-inhibitory concentrations. In the hamster and mouse models for CDAD, cadazolid was active, conferring full protection from diarrhea and death with a potency similar to that of vancomycin. These findings support further investigations of cadazolid for the treatment of CDAD.

Clostridial myonecrosis.

Clostridial infections, particularly myonecrosis, can be fulminant and fatal; they often arise without an obvious history of trauma. The cardinal diagnostic clues (Figure 3) must be recognized so that specific therapy can be initiated promptly and mortality can be minimized. Aggressive medical care, including crystalloid fluid therapy and antibiotics, must be initiated quickly. Vasopressors should be avoided. Antitoxin has no role in contemporary care. Early hyperbaric oxygenation is beneficial, but it should be preceded by decompressive fasciotomy if limb edema is marked. Otherwise, definitive debridement or amputation is best delayed until after hyperbaric therapy is begun. Regionalization of care and long transport times also must be considered seriously in determining the therapeutic approach.