Management and Outcomes in Children with Third-Generation Cephalosporin-Resistant Urinary Tract Infections.

BACKGROUND: Third-generation cephalosporin-resistant urinary tract infections (UTIs) often have limited oral antibiotic options with some children receiving prolonged parenteral courses. Our objectives were to determine predictors of long parenteral therapy and the association between parenteral therapy duration and UTI relapse in children with third-generation cephalosporin-resistant UTIs. METHODS: We conducted a multisite retrospective cohort study of children <18 years presenting to acute care at 5 children's hospitals and a large managed care organization from 2012 to 2017 with a third-generation cephalosporin-resistant UTI from Escherichia coli or Klebsiella spp. Long parenteral therapy was ≥3 days and short/no parenteral therapy was 0-2 days of concordant parenteral antibiotics. Discordant therapy was antibiotics to which the pathogen was non-susceptible. Relapse was a UTI from the same organism within 30 days. RESULTS: Of the 482 children included, 81% were female and the median age was 3.3 years (interquartile range: 0.8-8). Fifty-four children (11.2%) received long parenteral therapy (median duration: 7 days). Predictors of long parenteral therapy included age <2 months (adjusted odds ratio [aOR] 67.3; 95% confidence interval [CI]: 16.4-275.7), limited oral antibiotic options (aOR 5.9; 95% CI: 2.8-12.3), and genitourinary abnormalities (aOR 5.4; 95% CI: 1.8-15.9). UTI relapse occurred in 1 of the 54 (1.9%) children treated with long parenteral therapy and in 6 of the 428 (1.5%) children treated with short/no parenteral therapy (P = .57). Of the 105 children treated exclusively with discordant antibiotics, 3 (2.9%, 95% CI: 0.6%-8.1%) experienced UTI relapse. CONCLUSIONS: Long parenteral therapy was associated with age <2 months, limited oral antibiotic options, and genitourinary abnormalities. UTI relapse was rare and not associated with duration of parenteral therapy. For UTIs with limited oral options, further research is needed on the effectiveness of continued discordant therapy.

Clinical Response to Discordant Therapy in Third-Generation Cephalosporin-Resistant UTIs.

OBJECTIVES: To describe the initial clinical response and care escalation needs for children with urinary tract infections (UTIs) resistant to third-generation cephalosporins while on discordant antibiotics. METHODS: We performed a retrospective study of children <18 years old presenting to an acute care setting of 5 children's hospitals and a large managed care organization from 2012 to 2017 with third-generation cephalosporin-resistant UTIs (defined as the growth of ≥50 000 colony-forming units per mL of Escherichia coli or Klebsiella spp. nonsusceptible to ceftriaxone with a positive urinalysis). We included children started on discordant antibiotics who had follow-up when culture susceptibilities resulted. Outcomes were escalation of care (emergency department visit, hospital admission, or ICU transfer while on discordant therapy) and clinical response at follow-up (classified as improved or not improved). RESULTS: Of the 316 children included, 78% were girls and the median age was 2.4 years (interquartile range 0.6-6.5). Children were evaluated in the emergency department (56%) or clinic (43%), and 90% were started on a cephalosporin. A total of 7 of 316 children (2.2%; 95% confidence interval 0.8%-4.5%) experienced escalation of care. For the 230 children (73%) with clinical response recorded, 192 of 230 (83.5%; 95% confidence interval 78.0%-88.0%) experienced clinical improvement. In children with repeat urine testing while on discordant therapy, pyuria improved or resolved in 16 of 19 (84%) and urine cultures sterilized in 11 of 17 (65%). CONCLUSIONS: Most children with third-generation cephalosporin-resistant UTIs started on discordant antibiotics experienced initial clinical improvement, and few required escalation of care. Our findings suggest that narrow-spectrum empiric therapy is appropriate while awaiting final urine culture results.

HEPATIC OSTEODYSTROPHY IN A GOLDEN LION TAMARIN (LEONTOPITHECUS ROSALIA).

An 8-yr-old, captive, female golden lion tamarin ( Leontopithecus rosalia ) with a 6-yr history of hyperbilirubinemia was examined for inappetence and weight loss. Physical examination and blood pressure monitoring under anesthesia revealed hypothermia and hypotension, and blood work revealed hypoglycemia, markedly elevated liver enzymes, including serum alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase, and confirmed the hyperbilirubinemia. A complete blood count suggested chronic lymphoid leukemia. The animal's condition deteriorated during recovery, and the animal died despite aggressive treatment. Grossly, there was micronodular cirrhosis of the liver, severe icterus, and diffuse osteopenia of all examined bones. Microscopic examination of the liver confirmed the micronodular cirrhosis and bone lesions were compatible with diffuse osteopenia and osteomalacia. This brief communication presents a case of chronic liver disease and lesions indicative of metabolic bone disease, also known as hepatic osteodystrophy. To the authors' knowledge, this is the first documented case of hepatic osteodystrophy in the veterinary literature.

Differences in the rumen methanogen populations of lactating Jersey and Holstein dairy cows under the same diet regimen.

In the dairy cattle industry, Holstein and Jersey are the breeds most commonly used for production. They differ in performance by various traits, such as body size, milk production, and milk composition. With increased concerns about the impact of agriculture on climate change, potential differences in other traits, such as methane emission, also need to be characterized further. Since methane is produced in the rumen by methanogenic archaea, we investigated whether the population structure of methanogen communities would differ between Holsteins and Jerseys. Breed-specific rumen methanogen 16S rRNA gene clone libraries were constructed from pooled PCR products obtained from lactating Holstein and Jersey cows, generating 180 and 185 clones, respectively. The combined 365 sequences were assigned to 55 species-level operational taxonomic units (OTUs). Twenty OTUs, representing 85% of the combined library sequences, were common to both breeds, while 23 OTUs (36 sequences) were found only in the Holstein library and 12 OTUs (18 sequences) were found only in the Jersey library, highlighting increased diversity in the Holstein library. Other differences included the observation that sequences with species-like sequence identity to Methanobrevibacter millerae were represented more highly in the Jersey breed, while Methanosphaera-related sequences and novel uncultured methanogen clones were more frequent in the Holstein library. In contrast, OTU sequences with species-level sequence identity to Methanobrevibacter ruminantium were represented similarly in both libraries. Since the sampled animals were from a single herd consisting of two breeds which were fed the same diet and maintained under the same environmental conditions, the differences we observed may be due to differences in host breed genetics.

A comparison of the polycation receptors of Paramecium tetraurelia and Tetrahymena thermophila.

Chemorepellents are compounds that cause ciliated protozoans to reorient their swimming direction. A number of chemorepellents have been studied in the ciliated protozoans, Paramecium and Tetrahymena. Chemorepellents, such as polycations, cause the organism to exhibit "avoidance behavior," a swimming behavior characterized by jerky movements and other deviations from normal forward swimming, which result from ciliary reversal. One well-characterized chemorepellent pathway in Tetrahymena is that of the proposed polycation receptor that is activated by lysozyme and pituitary adenylate cyclase activating polypeptide (PACAP). In this study, we compare the response of Paramecium to the chemorepellents lysozyme, vasoactive intestinal peptide (VIP), and PACAP to the previously studied polycation response in Tetrahymena. Our results indicate that lysozyme, VIP, and PACAP are all chemorepellents in Paramecium, just as they are in Tetrahymena. However, the signaling pathways involved appear to be different. While previous pharmacological characterization indicates that G-proteins are involved in polycation signaling in Tetrahymena, we present evidence that similar reception in Paramecium involves activation of a tyrosine kinase pathway in order for lysozyme avoidance to occur. Polycation responses of both organisms are inhibited by neomycin sulfate. While PACAP is the most effective of the three chemorepellents in Tetrahymena, lysozyme is the most effective chemorepellent in Paramecium.