BackgroundLong‐duration beta‐lactam antibiotics are used for empirical treatment in female dogs with uncomplicated bacterial cystitis. However, women with bacterial cystitis are treated with short‐duration potentiated sulfonamides because longer courses of beta‐lactams result in lower cure and higher recurrence rates.Hypothesis/ObjectivesShort‐duration potentiated sulfonamide treatment is more efficacious than long‐duration beta‐lactam treatment in achieving clinical and microbiological cures in female dogs with uncomplicated bacterial cystitis.AnimalsThirty‐eight client‐owned female dogs.MethodsRandomized, double‐blinded, placebo‐controlled clinical trial. Dogs were treated with TMP‐SMX (15 mg/kg PO q12h for 3 days followed by a placebo capsule PO q12h for 7 days; Group SDS; n = 20) or cephalexin (20 mg/kg PO q12h for 10 days; Group LDBL; n = 18). Dogs were monitored for clinical and microbiological cure during treatment and at short‐ and long‐term follow‐up.ResultsNo statistically significant differences were found between treatment groups in clinical cure rates after 3 days of treatment (89% SDS, 94% LDBL; P = 1.00) and 4 days (85% SDS, 72% LDBL; P = .44) or >30 days (50% SDS, 65% LDBL; P = .50) after conclusion of treatment or in microbiological cure rates 4 days (59% SDS, 36% LDBL; P = .44) or >30 days (44% SDS, 20% LDBL; P = .40) after conclusion of treatment.Conclusions and Clinical ImportanceWe did not identify a difference in cure rates between short‐duration sulfonamide and long‐duration beta‐lactam treatments in female dogs with uncomplicated cystitis. Long‐term cure rates in both treatment groups were low. In some female dogs, “uncomplicated” bacterial cystitis may be more complicated than previously recognized.

Glutathione-S-transferase enzymes (GSTs) play an important role in the detoxification of environmental carcinogens. Defective GST genotypes are over-represented in human cancers; in particular, low activity GSTT1 genotypes are risk factors for non-Hodgkin lymphoma. We hypothesized that defective GSTT1 genotypes would be associated with lymphoma risk in dogs. To address this, we resequenced the exons, splice junctions, and 3'-UTR of canine GSTT1 in dogs with lymphoma (n = 93) and age-matched unaffected dogs (n = 86). Of 27 canine GSTT1 variants identified, the I2+28 G>A was significantly associated with lymphoma [odds ratio (OR) 6.26, 95% confidence interval (CI), 1.77-22.2], with the AA genotype found in 18.3% of affected dogs but only 3.5% of controls (P = 0.002). This intronic variant was predicted to perturb GSTT1 mRNA splicing, and may increase lymphoma risk by impairing detoxification of environmental chemicals. Confirmation of this finding in a larger population of dogs may support the inclusion of GSTT1 genotyping in epidemiologic studies of canine lymphoma risk.

Background Delayed hypersensitivity (HS) reactions to potentiated sulfonamide antimicrobials occur in both dogs and humans, and involve an intermediate hydroxylamine metabolite that is detoxified by cytochrome b5 and NADH cytochrome b5 reductase. Hypothesis/Objectives We hypothesized that polymorphisms in the genes (CYB5A and CYB5R3) encoding these 2 enzymes would be associated with risk of sulfonamide HS in dogs. Animals A total of 18 dogs with delayed HS to potentiated sulfonamide antimicrobials and 16 dogs that tolerated (TOL) a therapeutic course of these drugs without adverse effect. Methods CYB5A and CYB5R3 were sequenced from canine liver, and the promoter, exons, and 3′ untranslated regions of both genes were resequenced from genomic DNA obtained from all dogs. Results Multiple polymorphisms were found in both genes. When controlled for multiple comparisons, the 729GG variant in CYB5R3 was significantly overrepresented in dogs with sulfonamide HS (78% of dogs), compared to TOL dogs (31%; P = .003). Conclusions and Clinical Importance The CYB5R3 729GG variant may contribute to the risk of sulfonamide HS in dogs. Functional characterization of this polymorphism, as well as genotyping in a larger number of HS and TOL dogs, is warranted.

Cytochrome b(5) (b5) and NADH cytochrome b(5) reductase (b5R) detoxify reactive hydroxylamine (NHOH) metabolites of known arylamine and heterocyclic amine mammary carcinogens. The aim of this study was to determine whether NHOH reduction for the prototypic arylamine 4-aminobiphenyl (4-ABP) was present in human breast and to determine whether variability in activity was associated with single nucleotide polymorphisms (SNPs) in the coding, promoter, and 3'untranslated region (UTR) regions of the genes encoding b5 (CYB5A) and b5R (CYB5R3). 4-ABP-NHOH reduction was readily detected in pooled human breast microsomes, with a K(m) (280μM) similar to that found with recombinant b5 and b5R, and a V(max) of 1.12 ± 0.19 nmol/min/mg protein 4-ABP-NHOH reduction varied 75-fold across 70 individual breast samples and correlated significantly with both b5 (80-fold variability) and b5R (14-fold) immunoreactive protein. In addition, wide variability in b5 protein expression was significantly associated with variability in CYB5A transcript levels, with a trend toward the same association between b5R and CYB5R3. Although a sample with a novel coding SNP in CYB5A, His22Arg, was found with low reduction and b5 expression, no other SNPs in either gene were associated with outlier activity or protein expression. We conclude that b5 and b5R catalyze the reduction of 4-ABP-NHOH in breast tissue, with very low activity, protein, and messenger RNA expression in some samples, which cannot be attributed to promoter, coding, or 3'UTR SNPs. Further studies are underway to characterize the transcriptional regulation of CYB5A and CYB5R3 and begin to understand the mechanisms of individual variability in this detoxification pathway.

Streptococcus spp. are common causative organisms of endophthalmitis. Analysis of the clinical features, antibiotic susceptibilities, and outcomes of streptococcal endophthalmitis in children and adults may guide future management. Sixty-seven patients (67 eyes) with streptococcal endophthalmitis who were admitted to the Zhongshan Ophthalmic Center between January 2013 and December 2022 were retrospectively reviewed. The mean age was 20.7 ± 21.6 years, and 59.7% were children. Streptococcal infection accounted for 13.9% of culture-proven bacterial endophthalmitis cases; the proportion was higher in children than in adults (32.3% vs. 7.6%, p < 0.01) and increased from 8.1% in 2013–2017 to 20.1% in 2018–2022 (p < 0.01). Eye trauma was the most common etiology in both children and adults (82.5% and 66.7%, respectively). Viridans group streptococci were the most common isolates, followed by S. pneumoniae. The susceptibility rates of the streptococci to vancomycin, cefuroxime, and levofloxacin were 100%, 95.5%, and 93.0%, respectively. The overall mean best-corrected visual acuity increased from 2.74 ± 0.19 logMAR initially to 2.32 ± 0.75 logMAR at the last follow-up (p < 0.05). In conclusion, streptococcal infections have increased in cases of bacterial endophthalmitis in recent years and are more common in children. The commonly used antibiotics, vancomycin, cefuroxime, and fluoroquinolone, showed higher antibiotic susceptibility. After prompt treatment, visual outcomes improved.