Cystic fibrosis (CF) is characterized by recurrent airway infections with antibiotic-resistant bacteria and chronic inflammation. Chicken cathelicin-2 (CATH-2) has been shown to exhibit antimicrobial activity against antibiotic-resistant bacteria and to reduce inflammation. In addition, exogenous pulmonary surfactant has been suggested to enhance pulmonary drug delivery. It was hypothesized that CATH-2 when combined with an exogenous surfactant delivery vehicle, bovine lipid extract surfactant (BLES), would exhibit antimicrobial activity against CF-derived bacteria and downregulate inflammation. Twelve strains of CF-pathogens were exposed to BLES+CATH-2 in vitro and killing curves were obtained to determine bactericidal activity. Secondly, heat-killed bacteria were administered in vivo to elicit a pro-inflammatory response with either a co-administration or delayed administration of BLES+CATH-2 to assess the antimicrobial-independent, anti-inflammatory properties of BLES+CATH-2. CATH-2 alone exhibited potent antimicrobial activity against all clinical strains of antibiotic-resistant bacteria, while BLES+CATH-2 demonstrated a reduction, but significant antimicrobial activity against bacterial isolates. Furthermore, BLES+CATH-2 reduced inflammation in vivo when either co-administered with killed bacteria or after delayed administration. The use of a host-defense peptide combined with an exogenous surfactant compound, BLES+CATH-2, is shown to exhibit antimicrobial activity against antibiotic-resistant CF bacterial isolates and reduce inflammation.

Background: Antimicrobial resistance is a growing threat to the world’s ability to prevent and treat infections. Links between quantitative antibiotic use and the emergence of bacterial resistance are well documented. This study presents benchmark antimicrobial use (AMU) rates for inpatient adult populations in acute-care hospitals across Canada. Methods: In this retrospective surveillance study, acute-care adult hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP) submitted annual AMU data on all systemic antimicrobials from 2009 to 2016. Information specific to intensive care units (ICUs) and non-ICU wards were available for 2014–2016. Data were analyzed using defined daily doses (DDD) per 1000 patient days (DDD/1000pd). Results: Between 2009 and 2016, 16–18 CNISP adult hospitals participated each year and provided their AMU data (22 hospitals participated in ≥1 year of surveillance; 11 in all years). From 2009 to 2016, there was a significant reduction in use (12%) (from 654 to 573 DDD/1000pd, p = 0.03). Fluoroquinolones accounted for the majority of this decrease (47% reduction in combined oral and intravenous use, from 129 to 68 DDD/1000pd, p < 0.002). The top five antimicrobials used in 2016 were cefazolin (78 DDD/1000pd), piperacillin-tazobactam (53 DDD/1000pd), ceftriaxone (49 DDD/1000pd), vancomycin (combined oral and intravenous use was 44 DDD/1000pd; 7% of vancomycin use was oral), and ciprofloxacin (combined oral and intravenous use: 42 DDD/1000pd). Among the top 10 antimicrobials used in 2016, ciprofloxacin and metronidazole use decreased significantly between 2009 and 2016 by 46% (p = 0.002) and 26% (p = 0.002) respectively. Ceftriaxone (85% increase, p = 0.0008) and oral amoxicillin-clavulanate (140% increase, p < 0.0001) use increased significantly but contributed only a small component (8.6 and 5.0%, respectively) of overall use. Conclusions: This study represents the largest collection of dispensed antimicrobial use data among inpatients in Canada to date. Between 2009 and 2016, there was a significant 12% decrease in AMU, driven primarily by a 47% decrease in fluoroquinolone use. Modest absolute increases in parenteral ceftriaxone and oral amoxicillin-clavulanate use were noted but contributed a small amount of total AMU. Ongoing national surveillance is crucial for establishing benchmarks and antimicrobial stewardship guidelines.

Sepsis has seen an incremental increase in cases of about 13% annually in the USA and accounts for approximately 4400 deaths among pediatric patients. Early identification of the specific pathogen allows the clinician to ensure that the antibiotic coverage is optimal, an intervention that has been shown to improve patient outcomes in sepsis. Our study’s objective was to assess the impact of a rapid Bruker MALDI-Tof identification protocol on pediatric sepsis cases by assessing various indicators. We assessed the quality of care by measuring the following indicators; time to identification of the pathogen, initiation of the most appropriate antibiotic, length of stay (LOS) in hospital and patient outcomes, using a retrospective review over three consecutive years. In total 92 pediatric patients, similar in age and gender distributions were assessed; 37 in 2012, 33 in 2013 and 22 in 2014. The introduction of MALDI-TOF identification in 2013 led to a significant decrease in time to identify a pathogen by 21.03 hours (p = 1.95E-05). A short incubation MALDI-TOF identification protocol in 2014 further reduced time to identification by 17.75 hours (p = 2.48E-3). Overall in 2014 this led to a trend to earlier optimization of antibiotics by 20.2 hours (p = 0.14) and a reduction in length of stay after the implementation of MALDI-ToF identification in 2013 of 3.07 days and a further reduction of 8.92 days after the introduction of the rapid short incubation identification protocol using MALDI-Tof in 2014 (P = 0.12). By evaluating the subgroup of patients where antibiotics were changed, our study confirmed that patients received appropriate therapy 48.8% (20.2 hours) earlier compared to conventional methods leading to a decrease in length of stay of 23.65 days after the implementation of MALDI-ToF identification and a further reduction of 9.82 days in 2014 compared to 2012 (p = 0.02). In 2014 outcomes between the patients needing a change in their antibiotic compared to the patients where the empirical therapy was considered to be optimal were similar with respect to length of stay; 13.04 and 10.93 days (p = 0.34). In the 2012 group there was a significant increase in the length of stay in the group needing change in excess of 30 days (p = 0.02) compared to the group where empirical therapy was considered to be optimal, this clearly showed an improvement in the quality of care received after the rapid identification was instituted in 2014. The 2012 group had a four times overall increased sepsis associated mortality risk compared to the 2014 group and when empirical antibiotics needed to be optimized this risk was 7 times compared to the 2014 group. We conclude that rapid identification of bacterial pathogens in pediatric blood cultures with a rapid incubation MALDI-TOF identification protocol plays an important role in improving quality of care as part of a multidisciplinary approach to pediatric bacteremia and sepsis.

Fournier’s gangrene is a rare necrotizing soft tissue infection of the scrotum and penis. We report, to our knowledge, the first case of Fournier’s gangrene caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE), a strain of pyogenic β-hemolytic streptococci that is increasingly being recognized as an important human pathogen.

Renal infarction is a rare finding in children. Associations between SARS-CoV-2 infections and thromboembolic events including renal infarcts have been described in adults. Although a similar association in children has not yet been described with this pandemic, the pediatric literature is still evolving with the recognition of new manifestations including the post-infectious Multisystem Inflammatory Syndrome in Children (MIS-C). We report the rare event of multiple renal infarcts in a 6-year-old boy manifesting several features of MIS-C 9 weeks following a self-limiting febrile illness characteristic of COVID-19. An underlying Factor V Leiden mutation was identified in this child but felt to be insufficient on its own to explain his clinical presentation. As SARS-CoV-2 testing was delayed, the failure to identify viral RNA or antibodies may not exclude the virus' potential role in precipitating the infarct in this host. Given that renal infarcts have been described in adult patients with COVID-19, reporting this perplexing case where SARS-CoV-2 may have played a role, may help identify this potential complication.