Critical Aspects in the Preparation of Extemporaneous Flecainide Acetate Oral Solution for Paediatrics

The availability of liquid oral preparations compounded by pharmacists is essential to meet paediatric needs which remain unanswered by the pharmaceutical industry. Unfortunately, compendial monographs are often not available and, in many cases, pre-formulation studies (e.g., compatibility with other excipients and solubility evaluations) are not performed in-depth, leading, in some rare cases, to the inadvertent administration of a toxic dose. In this study, the preparation of an oral liquid formulation for paediatric use, containing flecainide acetate at different strengths, was considered, taking into account the possible effects of conventionally used excipients. First, the optimal vehicle was selected based on a solubility study, evidencing some unexpected formations of precipitates. As a matter of fact, the buffers commonly used for oral solutions significantly reduced flecainide solubility, and the concomitant presence of citrate buffer and methylparaben even caused the formation of non-resuspendable crystals. Then, chemical, physical, and microbiological stability were assessed. Solutions at strengths of 10 and 20 mg/mL flecainide acetate were stable up to 8 weeks when compounded by using a 40% sucrose solution as a vehicle. Microbiological data showed that the use of methylparaben was not necessary over this time period.

222. Clinical and Microbiological Characteristics of Common Bacterial Bloodstream Infections in the US Military Health System

Background Bloodstream infections (BSI) are associated with inpatient morbidity in the United States. We sought to characterize the epidemiology of common bacterial BSIs in individuals receiving care within the US Military Health System (MHS), which actively prospectively captures clinical and microbiological data from both retired and active-duty US Uniformed Service members and their beneficiaries. Methods We performed a retrospective cohort study analyzing MHS patients with blood cultures positive for all bacterial pathogens, between January 2010 and December 2019. Microbiological data captured by the Navy and Marine Corpse Public Health Center, excluding cultures isolating contaminants, were retrospectively collated with clinical and demographic data from the MHS Data Repository. Results The most frequent nine bacterial pathogens, as well as Acinetobacter spp. represented 17,206 episodes of BSI from 14,531 individuals. The cohort was predominantly male (59.4%) and ≥65 years old (48.7%). Most individuals were retired (N=5,249) or active duty (N=1,418) service members and their dependents (N=5,236). Median Updated Charlson Comorbidity Index Score was 2. Chronic pulmonary disease was the most frequent comorbid condition. Hospital admission was associated with 13,733 (79.8%) BSI episodes, including 5,870 admissions to the ICU. Overall, inpatient mortality was 8.3%. E. coli (29.7%, N= 5,114) was isolated with the highest frequency, followed by S. aureus (22.4%, N=3,853). Further, 9.5% of E. coli and 36.9% of S. aureus isolates were resistant to ceftriaxone and oxacillin, respectively. Beta-hemolytic streptococci represented the highest percentage (6.3%) of recurrent BSI episodes occurring at least 14 days post-initial BSI. Males or Native American race were most commonly infected with S. aureus. E. coli BSI was most common in all other demographic categories. Frequency of Bacterial Blood Stream Infections in the US Military Health System The most frequent nine bacterial pathogens, as well as Acinetobacter spp. in the US Military Health System. Conclusion We assessed the epidemiologic features of all individuals with BSI receiving care in the MHS over a 10-year period. We noted demographic differences in the occurrence of microbiological causes of BSI including S. aureus. Further assessments are underway into BSI-related risk factors for occurrence, antimicrobial resistance and mortality, after controlling for comorbidities and disease severity. Disclosures All Authors: No reported disclosures

304. Impact of Antibiotic Prophylaxis Prior to Treatment with Steroids and Tocilizumab in COVID-19 Patients

Background The incidence of bacterial or fungal coinfections in COVID-19 patients is low. The incidence of nosocomial superinfections is higher, especially related to ICU admission. Treating COVID-19 with steroids plus tocilizumab (TCZ) has been associated with superinfections. Therefore, the use of antibiotic prophylaxis prior to infusion of TCZ could be considered to reduce the risk of life-threatening superinfections in critically ill patients. Methods Retrospective, single center cohort study. COVID-19 patients older than 14 years, admitted to Hospital Central de la Defensa (Madrid, Spain) from Mar 5th to Nov 24th, 2020 with a diagnosis of COVID-19 were included. Local protocols suggested antimicrobial prophylaxis before the infusion of TCZ. Medical records, treatments received, and microbiological data of all patients who received TCZ were reviewed. Microbiological isolates were considered in the 14 days following the administration of TCZ. Two ID specialists independently reviewed the medical record and decided to qualify the isolate as superinfection or colonization. Results 2,069 patient records were analyzed. 70 patients received TCZ; all of them were admitted to ID wards and under steroid treatment. 45 (64,5%) patients received antibiotic prophylaxis. The preferred antibiotics were ceftriaxone (N = 18) and ceftobiprole (N = 14). No significant differences were found in age, Charlson index or COVID-19 SEIMC-Score. 24 isolates were detected in 14 patients (18 bacterial, 6 fungal). 17 isolates were considered superinfections; the most frequent isolates were C. albicans (N=5), E. faecalis (N=3) and S. epidermidis (N=2). There were no statistically significant differences between the different prophylaxis strategies in terms of in-hospital mortality or ICU admission. However, patients who received ceftobiprole tended to have fewer isolates and fewer superinfections than those receiving ceftriaxone (ceftobiprole group: 2 isolates in 1 patient, 1 (7,1%) patient with superinfection; ceftriaxone 11 isolates in 5 patients, 4 (22,2%) patients with superinfection) (p= 0,35, Fisher exact test). Table 1. Characteristics of study population. Table 2. Outcomes according to antimicrobial prophylaxis prior to Tocilizumab. Table 3. Description of isolates. Conclusion Antibiotic prophylaxis prior to infusion of TCZ in patients with COVID-19 and receiving steroids could determine the profile of bacterial and fungal superinfections. Disclosures All Authors: No reported disclosures

A Survey of Cheese from Small-Scale Artisanal Producers in Western Cape, South Africa

The objective of this study was to assess cow milk cheese from small-scale producers in the Western Cape Province, South Africa. Forty cheeses were selected, and microbiological data of the samples were analyzed with age (1, 3, 6 months), cheese type (Cheddar, Gouda, other), and milk type (raw and pasteurized) as main factors. Rapid sensory characterization was done using the sorting technique. The results indicated that the available cheese types were diverse, with minority (20.0%) in the Gouda group followed by Cheddar (32.5%) and “other” (47.5%). Most of these cheeses (45%) were aged three months and produced using pasteurized milk (92.5%). Five cheese samples did not meet the European Union standards for coliforms, and four samples tested positive for Escherichia coli. Sensory analysis results showed a clear differentiation between mature and young cheese. In conclusion, the current market presents more diverse milder cheeses, and there is a need to follow proper hygiene protocols to reduce cross-contamination.

Heatwave-associated Vibrio infections in Germany, 2018 and 2019

Background Vibrio spp. are aquatic bacteria that prefer warm seawater with moderate salinity. In humans, they can cause gastroenteritis, wound infections, and ear infections. During the summers of 2018 and 2019, unprecedented high sea surface temperatures were recorded in the German Baltic Sea. Aim We aimed to describe the clinical course and microbiological characteristics of Vibrio infections in Germany in 2018 and 2019. Methods We performed an observational retrospective multi-centre cohort study of patients diagnosed with domestically-acquired Vibrio infections in Germany in 2018 and 2019. Demographic, clinical, and microbiological data were assessed, and isolates were subjected to whole genome sequencing and antimicrobial susceptibility testing. Results Of the 63 patients with Vibrio infections, most contracted the virus between June and September, primarily in the Baltic Sea: 44 (70%) were male and the median age was 65 years (range: 2–93 years). Thirty-eight patients presented with wound infections, 16 with ear infections, six with gastroenteritis, two with pneumonia (after seawater aspiration) and one with primary septicaemia. The majority of infections were attributed to V. cholerae (non–O1/non-O139) (n = 30; 48%) or V. vulnificus (n = 22; 38%). Phylogenetic analyses of 12 available isolates showed clusters of three identical strains of V. vulnificus, which caused wound infections, suggesting that some clonal lines can spread across the Baltic Sea. Conclusions During the summers of 2018 and 2019, severe heatwaves facilitated increased numbers of Vibrio infections in Germany. Since climate change is likely to favour the proliferation of these bacteria, a further increase in Vibrio-associated diseases is expected.

Infections of scleroderma digital ulcers: a single center cohort retrospective study

BACKGROUNDS: Systemic Sclerosis (SSc) is a complex autoimmune and up to fifty percent of patients develop digital ulcers. AIMS: Understand how much infections influence scleroderma digital ulcers’ healing. METHODS: We revised fifty consecutive patients with SSc-related DUs who referred to our Scleroderma Unit. Thirty-five of them who showed clear signs of DUs infection underwent to cutaneous swab and microbiological data collection. We performed 87 cutaneous swabs overall. RESULTS: DUs were recurrent in 58% of the patients and multiple in 60% of patients. Fourty-four swabs (53%) were positive for Staphylococcus Aureus (13% Methicillin-Resistant), 9 were positive for Pseudomonas Aeruginosa (Pseudomonas A.) (10%), and then the others less frequently isolated. Twenty-fifth percent of patients needed hospitalization. CONCLUSIONS: Our data support a patient-tailored approached to DUs, particularly those infected. Self-hygiene and asepsis during dressing procedures are mandatory. Patient must be trained to avoid dangerous behaviors and reduce the risk of infection.

Mapping of physical-chemical, microbiological, and chemical component characteristics of water samples from Nile tilapia slaughterhouses

The aim of this study was to analyze the physicochemical and microbiological characteristics of the water used in fish processing and tilapia fillets in slaughterhouses. The study analyzed the processing water from nine slaughterhouses. The water samples for analysis were collected at three points: process water (PW), it is the water used inside the slaughterhouses in direct contact with the fish; clean water entering the purification tank (EPT) and water leaving the purification tank (LPT). The processing waters of the nine tilapia slaughterhouses were analyzed and characterized according to their microbiological and physical-chemical characteristics. The results of microbiological analyzes meet the values indicated by legislation, in most cases. Regarding microbiological data, we can highlight that there was an increase in the total coliforms of the water entering the purification tank to the water leaving the purification tank in five slaughterhouses. Still, there was an increase in the aerobic mesophilic bacteria content observed in the outgoing water in relation to the inlet water of the purification tank in seven slaughterhouses. In relation to the physical chemical analyzes for the process water samples, the results show that the evaluated indices are in accordance with the values indicated by the legislation. The levels of Cd, Mg, Sc and Cd were below that detectable by the analysis in all slaughterhouses. The levels of Al, Sc, As, Rb, Ba, Pb, Mn, As, Se, Rb, Ag, Sb, Ba and Pb were detected only in one or two slaughterhouses. It is concluded that although some abattoirs have water characteristics outside the limits indicated by the legislation, the observed changes were not significant and small adjustments are necessary for the adequacy.

Stormwater Monitoring Using On-line UV-Vis Spectroscopy for Surrogate Measurements of Chemical Contaminants and Compared With Microbiological Data

Stormwater runoff contains a myriad of pollutants, including faecal microbes, and can pose a threat to urban water supplies, impacting both economic development and public health. Therefore, it is a necessity to implement a real-time hazard detection system that can collect a substantial amount of data, assisting water authorities to develop preventive strategies to ensure the control of hazards entering drinking water sources. An on-line UV-Vis spectrophotometer was applied in the field to collect real-time continuous data for various water quality parameters (nitrate, DOC, turbidity and total suspended solids) during three storm events in Mannum, Adelaide, Australia. This study demonstrated that the trends for on-line and comparative laboratory analysed samples were complimentary through the events. Nitrate and DOC showed a negative correlation with water level while turbidity and total suspended solids indicated a positive correlation with water level during the high rainfall intensity. The correlations among nitrate, DOC, turbidity, total suspended solids, and water level are the opposite during the low rainfall intensity. Nitrate, one of the main pollutants in stormwater, was investigated and used as a surrogate parameter for microbial detection. However, the microbiological data (E.coli) from captured storm events showed poor correlations to nitrate and other typical on-line parameters in this study, possibly explained by the nature of the stormwater catchment outside of rain events, where the sources of bacteria and nutrients may be physically separate until mixed during surface runoff as a result of rainfall. In addition, the poor correlations among the microbiological data and on-line parameters can be due to the different sources of bacteria and nutrients that end up into the stormwater drain.

Microbial profile in infectious keratitis over 8 years in Sao Paulo, Brazil: pathogens and microbial resistance

Objective Infectious keratitis remains a sight-threatening disease and its prompt diagnosis and treatment are critical. This study investigated the microbiological patterns of isolates in corneal ulcers in a tertiary health center in an 8-year period. Methods Retrospective analysis of scrapes of microbial keratitis performed from January 2013 to December 2020. Demographics and microbiological data were collected. Results A total of 446 scrapes were performed on eyes of 433 patients, 270 male (62.4%), mean age 51.7 years. 304 organisms were isolated from 248 (55.6%) positive samples. Polymicrobial infections occurred in 47 samples (19.0%). Bacterial isolates represented 86.8%: 53.3% gram-positive (GP), 33.5% gram-negative (GN). Cutibacterium acnes (12.2%) and Pseudomonas aeruginosa (9.9%) were the most common bacteria. Fungal keratitis comprised 11.8% of the isolates; Fusarium sp (6.2%) was the main fungus isolated. GP tested were sensitive to vancomycin, 98.7% of the GN were sensitive to ceftazidime. All Pseudomonas aeruginosa were sensitive to gentamicin and ciprofloxacin. Conclusion Gram-positive bacteria were predominant in keratitis isolates. In severe bacterial keratitis in our area, vancomycin should be considered as empirical treatment.