1110. In Vivo Pharmacodynamics of Vancomycin Against Staphylococci in Young Infants

Background Coagulase-negative staphylococci are the predominant pathogen causing late onset sepsis in young infants, however, the pharmacodynamic target for vancomycin therapy is unknown. This study aimed to determine the pharmacodynamic target of vancomycin in young infants with staphylococcal infections. Methods Retrospective data were collected for infants aged 0-90 days with methicillin-resistant Staphylococcus aureus (MRSA or coagulase-negative staphylococci (CoNS) bacteraemia over a 4-year period at the Royal Children’s Hospital Melbourne, Australia. Vancomycin broth microdilution minimum inhibitory concentrations (MIC) were determined. A published pharmacokinetic model was externally validated using the study dataset and a time-to-event pharmacodynamic model developed using non-linear mixed effects modelling, with the event being the first negative blood culture. Simulations were performed to determine the 24-hour trough vancomycin concentration correlating with a 90% probability target attainment (PTA) of the area under the curve in the first 24-hours (AUC0-24) exceeding the identified target. Results Thirty infants, 28 with CoNS and two with MRSA bacteraemia, who had 165 vancomycin concentrations determined were included. The vancomycin broth microdilution MIC was determined for 24 CoNS and one MRSA isolate, both with a median MIC of 1 mg/L (CoNS range 0.5 to 4). An AUC0-24 ≥3 00 mg/L·h was associated with a 7.8-fold increase in the chance of bacteriological cure for all staphylococci at any time point compared to an AUC0-24 < 300 mg/L·h (hazard ratio 95% CI: 3.21-18.8). The 24-hour trough concentrations associated with a 90% PTA of achieving this target were > 13-16 mg/L and > 8-12 mg/L for 6 and 12-hourly dosing, respectively. Conclusion Our study found that an AUC0-24 ≥ 300 mg/L·h was associated with a 7.8-fold increase in bacteriological cure in young infants with staphylococcal bloodstream infections. Disclosures All Authors: No reported disclosures

Anti-Inflammatory and Antibacterial Potential of Qicao Rukang Powder in Bovine Subclinical Mastitis

Background. Subclinical mastitis is one of the most common reproductive diseases in dairy cows. Qicao Rukang powder is a Chinese herbal compound mixture developed to treat subclinical mastitis in dairy cows by clearing heat, tonifying qi, and improving blood and milk circulation. The study aimed to determine the anti-inflammatory and antimicrobial efficacy of Qicao Rukang powder in treating subclinical mastitis in dairy cows at the manufacturer’s recommended dose. Methods. Forty (40) Holstein dairy cows with milk somatic cell count (SCC) ≥ 500,000 cellml−1 were randomly assigned to treatment (n = 20) and control (n = 20) groups. Cows in the treatment group were administered with 150 grams of Qicao Rukang powder orally for five days, while the control group received no treatment. The authors analyzed the milk SCC, milk composition, bacteriological cure rate of the drug, blood serum levels of interleukins (IL-6, IL-1β, and IL-8), tumor necrosis factor (TNF-α), and interferon gamma (INF-γ) quantified by using ELISA kits on day 0 and day 6. Results. SCC of the treated group reduced very significantly ( P < 0.001 ) compared with the control group. Milk fat, protein, and total solids increased significantly ( P < 0.05 ) after treatment, whereas lactose and milk urea nitrogen levels showed a nonsubstantial rise. The bacteriological cure percentage of Qicao Rukang powder therapy was 77.8% for Aeromonas spp. (14 of 18), 75% for Pseudomonas spp. (6 of 8), and 100% for Acinetobacter spp. and Enterococcus spp. giving 81.8% cured for all isolates (27 of 33). Only 26.7% (8 of 30) of untreated cows recovered spontaneously. Analysis of IL-1β, IL-6, and INF-γ in the blood serum of the treated group revealed a significant decrease ( P < 0.01 ) with nonsignificant rises in TNF-α and IL-8 levels. Conclusions. This research demonstrates that Qicao Rukang powder has potent antibacterial and anti-inflammatory actions, supporting its use as an alternative to conventional treatment for subclinical dairy cow mastitis. However, further investigations will be required to explain the role of the active ingredients and the mechanisms involved in the pharmacological activities of the Qicao Rukang powder.

The Clinical Efficacy of Nitrofurantoin for Treating Uncomplicated Urinary Tract Infection in Adults: A Systematic Review of Randomized Control Trials

<b><i>Objective:</i></b> To provide an updated systematic review of randomized control trials (RCTs) to investigate the clinical and microbiological efficacy of nitrofurantoin compared to other antibiotics or placebo for treatment of uncomplicated urinary tract infections (uUTI). A secondary aim is to assess whether nitrofurantoin use is associated with increased side effects compared to other treatment regimens. <b><i>Summary:</i></b> The review was performed according to PRISMA guidelines. We searched 4 databases for articles published from database inception to May 6, 2020: (1) PubMed electronic database of the National Library of Medicine, (2) Web of Science, (3) Embase, and (4) Cochrane Library. Nine RCTs were selected for the review. RCTs were a mixture of double-blind, single-blind, and open-label trials. The most common comparators were trimethoprim-sulfamethoxazole and fosfomycin tromethamine. Overall study quality was poor with a high risk of bias. The clinical cure rates in nitrofurantoin ranged from 51 to 94% depending on the length of follow-up, and bacteriological cure rates ranged from 61 to 92%. Overall the evidence suggests that nitrofurantoin is at least comparable with other uUTI treatments in terms of efficacy. Patients taking nitrofurantoin reported fewer side effects than other drugs and the most commonly reported were gastrointestinal and central nervous system symptoms. <b><i>Key Messages:</i></b> Evidence on the clinical and bacteriological efficacy of nitrofurantoin is sparse, with a lack of new data, and hampered by high risk of bias. Although no firm conclusions can be made on the current base of evidence, the studies generally suggest that nitrofurantoin is at least comparable to other common uUTI treatments in terms of clinical and bacteriological cure. More robust research with well-designed double-blinded RCTs is needed.

Responding to questions about clinical mastitis treatment failure on farm: improving the outcome

The treatment of clinical mastitis on farm is always under the spotlight for veterinary surgeons due to the financial penalty of withholding milk from the bulk tank, the challenge of achieving a bacteriological cure during lactation compared with during a dry period and the importance of antibiotic use in dairy herds. This article focuses on the management of the FIRST clinical mastitis case in a cow's lactation, as this not only represents the best chance of achieving a bacteriological cure as well as a symptomatic one, but also puts emphasis on the need to measure the outcome of treatment approaches for first cases and the likely origin of first cases so that treatment can be avoided in the future.

Treatment of uncomplicated UTI in males: a systematic review of the literature.

Background: Urinary tract infections (UTI) affect around 20% of the male population in their lifetime. The incidence of UTI in men in the community is 0.9 to 2.4 cases per 1,000 under the age of 55 years and 7.7 per 1,000 over 85 years. Aim: To evaluate the outcomes of randomised controlled trials (RCTs) comparing the effectiveness of different antimicrobial treatments and durations for uncomplicated UTIs in adult males in outpatient settings. Method: RCTs of adult male patients with an uncomplicated UTI treated with oral antimicrobials in any outpatient setting. The outcomes were symptom resolution within two weeks of starting treatment, duration until symptom resolution, clinical cure, bacteriological cure and frequency of adverse events. Results: From the 1041 abstract screened, 3 provided sufficient information on outcomes. One study compared trimethoprim-sulfamethoxazole for 14 days with 42 days in 2*21 males. Fluoroquinolones were compared in the two other studies: lomefloxacin (10 males) with norfloxacin (11 males), and ciprofloxacin for 7 and 14 days (2*19 males). Combining the results from the three studies shows that for 75% males with a UTI (76/101) bacteriological cure was reported at the end of the study. Of the 59 patients receiving a fluoroquinolone, 57 (97%) reported bacteriological and clinical cure within 2 weeks after treatment. Conclusion: The evidence available is insufficient to make any recommendations in relation to type and duration of antimicrobial treatment for male UTIs. Sufficiently powered RCTs are needed to identify best treatment type and duration for male UTIs in primary care.

Evaluation of fully oxidized β-carotene as a feed ingredient to reduce bacterial infection and somatic cell counts in cows with subclinical mastitis

AimsTo assess the effect of oral supplementation with fully oxidised β-carotene (OxBC) on bacteriological cure, incidence of clinical mastitis, and somatic cell counts (SCC) in cows with subclinical intramammary infection.MethodsCows from four dairy herds were enrolled in early lactation if they had quarter-level SCC >200,000 cells/mL and they had a recognised bacterial intramammary pathogen in one or more quarters. They were randomly assigned to be individually fed from Day 0, for an average of 40 days, with 0.5 kg of a cereal-based supplementary feed that either contained 300 mg of OxBC (treatment; n=129 quarters) or did not (control; n=135 quarters). Quarter-milk samples were collected on Days 21 and 42 for microbiology and SCC assessment. Bacteriological cure was defined as having occurred when the bacteria present on Day 0 were not isolated from samples collected on Days 21 or 42. Clinical mastitis was diagnosed and recorded by herdowners up to Day 42.ResultsThe bacteriological cure rate was greater for quarters from cows in the treatment group (13.9 (95% CI=4.1–23.7)%) than for quarters from cows in the control group (6.9 (95% CI=4.8–9.1)%; p=0.02). The prevalence of quarters that were infected on Day 42 was less in cows in the treatment group (79.9 (95% CI=62.3-97.6)%) than the control group (88.2 (95% CI=78.4-97.9)%; p=0.009). The incidence of quarters diagnosed with clinical mastitis by Day 42 was lower in cows from the treatment group (1/129 (0.78 (95% CI=0.02-4.24)%) than in cows from the control group (6/135 (4.44 (95% CI=1.65-9.42)%; p=0.03). Mean quarter-level SCC did not differ between treatment groups (p=0.34).Conclusions and Clinical RelevanceFeeding 300 mg/cow/day of fully oxidised β-carotene resulted in a higher bacteriological cure rate, a lower prevalence of intramammary infection following 6 weeks of feeding, and a lower incidence of clinical mastitis compared to untreated controls. This offers a non-antimicrobial approach to reducing prevalence of intramammary infection in dairy cows.

Internal Teat Sealant Administered at Drying off Reduces Intramammary Infections during the Dry and Early Lactation Periods of Dairy Cows

The effect of an internal teat sealant (ITS) on subsequent infection of the mammary gland was evaluated on the following mammary gland health indicators: (a) bacteriological cure of preexisting intramammary infections at drying off, (b) risk of postpartum new intramammary infections (NIMI), (c) cure and risk of new cases of subclinical mastitis (SCM), and (d) risk of postpartum clinical mastitis (CM). A total of 553 cows during late gestation were randomly assigned into two treatment protocols at drying off: (a) Dry cow therapy with 0.25 g of intramammary anhydrous cefalonium (ADCT; Cepravin®, MSD Animal Health); or (b) ADCT combined with ITS (SDCT; 4 g bismuth subnitrate; Masti-Seal®, MSD Animal Health, São Paulo, Brazil). Mammary quarter (MQ) milk samples were collected for microbiological culture and somatic cell count (SCC) at drying off and early lactation, and data from 1756 MQ were used in the multivariate logistic regression. There was no effect on the risk of bacteriological cure, SCM cure, and new cases of postpartum SCM. Still, SDCT reduced the risk of CM up to 60 days postpartum (DPP), overall NIMI risk, and the NIMI caused by major pathogens compared to ADCT. Thus, the DCT combined with ITS at drying off is effective for preventing NIMI during the dry period and CM up to 60 DPP.

Factors associated with microbiological and clinical cure of mastitis in dairy cows

ABSTRACT 709 clinical mastitis cases were analyzed and treated with antimicrobial combination cephalexin-neomycin and the anti-inflammatory prednisolone. A sample of milk was collected to perform a microbiological culture before starting the treatment and 14 days later. Somatic cell count (SCC) was obtained from samples collected on the day of the clinical case (D0), 14 days after (D14) and 28 days after (D28). Of the total, 435 (61.4%) at the D0 exhibited growth of microorganisms. Of the isolated agents, 365 (84%) were Gram-positive, and 66 (16%) were Gram-negative. A clinical cure was achieved in 63% of cases. Bacteriological cure occurred in 75% of cases. Only at D28 after the clinical case a significant SCC reduction was verified. The logistic regression for clinical cure showed significant effects for days in milk and parity (P< 0.05). For bacteriological cure, there were significant effects of Log (SCC) D0; clinical cure and quarter affected (P< 0.05). In the principal component analysis, the Temperature-Humidity Index was associated with reduced clinical cure of clinical mastitis cases.