USO INDISCRIMINADO DE ANTIBIÓTICOS NA CLÍNICA VETERINÁRIA, SELEÇÃO DE BACTÉRIAS MULTIRRESISTENTES E RISCO PARA A SAÚDE PÚBLICA – ESTUDO DE CASO

Introdução. A resistência aos antibióticos em pets é crescente. Prescrições indevidas, utilizando medicamentos não indicados, em dosagem ou por tempo inadequado e automedicação são realidades comuns. Alguns trabalhos vêm monitorando a resistência microbiana em cães saudáveis ou doentes. Objetivo. Investigar e relatar o caso clínico de infecção urinária canina multirresistente por Corynebacterium urealyticum com consequente contaminação humana. Material e métodos. O cão contaminado era macho, castrado, de 1 ano. Fez uso de antibiótico apenas no pós cirúrgico da castração, com 2 meses e, com 1 ano, em uma cirurgia de grande porte. No último episódio, na internação foi administrada ceftriaxona e posterior amoxicilina com clavulanato. Ambos os medicamentos de amplo espectro foram utilizados por período inadequado, onde já apresentou sintomas de cistite. Em casa, uma semana após a retirada do último antibiótico, foi realizada ultrassonografia com cistocentese e iniciado o tratamento com enrofloxacino e posteriormente, com a manutenção dos sintomas, com doxiciclina até o resultado do teste de suceptibilidade a antibióticos (TSA). Além disso, foram coletadas amostras de esfregaço nasofaríngico de coabitantes humanos da casa desses animais. Resultados. Na urina do cão foi isolada Corynebacterium urealyticum, bactéria de prevalência baixa, normalmente restrita a infecções em humanos imunocomprometidos. Recentemente foi relatado em cães e gatos domésticos. A cistite era necro-hemorrágica crônica difusa grave, com demasiados depósitos, obstruções e hidronefrose. O TSA indicou resistência a ampicilina, ciprofloxacina, clindamicina, doxiciclina, enrofloxacina, eritromicina, gentamicina, levofloxacina, marbofloxacina, norfloxacina, penicilina, rifampicina, tetraciclina e sensibilidade apenas à vancomicina, amicacina e linezolida. O tratamento clínico com amicacina não foi eficaz, havendo piora do paciente, necessitando de intervenção cirúrgica, onde se verificou ruptura vesical e peritonite. Posterior, o tratamento com vancomicina foi eficiente. Além disso, a bactéria encontrada no animal, com os mesmos padrões de resistência, também contaminava um dos humanos da residência, assintomática. Conclusão. O caso clínico exemplifica um grave caso de resistência antimicrobiana e que o risco do uso indiscriminado de antibióticos na veterinária é também para a saúde pública.

Vasovagal reaction secondary to bladder overdistension in a dog undergoing a unique timeline of medical and surgical treatment for Corynebacterium urealyticum encrusting cystitis: a case report

Background Corynebacterium urealyticum urinary tract infections can result in a rarely reported condition called encrusting cystitis whereby plaque lesions form on and within the urinary bladder mucosa. Chronic lower urinary tract signs manifest subsequent to the infection-induced cystitis and plaque-induced decreased bladder wall distensibility. Because of the organism’s multidrug resistance and plaque forming capability, infection eradication can be difficult. While systemic antimicrobial therapy is the mainstay of treatment, adjunctive surgical debridement of plaques has been used with relative paucity in such cases, thereby limiting our understanding of this modality’s indications and success rate. Consequently, this report describes the successful eradication of Corynebacterium urealyticum encrusting cystitis utilizing a unique timeline of medical and surgical treatments. Additionally, this represents the first reported veterinary case of a vasovagal reaction due to bladder overdistension. Case presentation A 6-year-old female spayed Miniature Schnauzer was evaluated for lower urinary tract clinical signs and diagnosed with Corynebacterium urealyticum encrusting cystitis. The infection was persistent despite prolonged courses of numerous oral antimicrobials and urinary acidification. A unique treatment timeline of intravenous vancomycin, intravesical gentamicin, and mid-course surgical debridement ultimately resulted in infection resolution. During surgery, while the urinary bladder was copiously flushed and distended with saline, the dog experienced an acute vasovagal reaction from which it fully recovered. Conclusions Surgical debridement of bladder wall plaques should be considered a viable adjunctive therapy for Corynebacterium urealyticum encrusting cystitis cases failing to respond to systemic antibiotic therapy. The timing in which surgery was employed in this case, relative to concurrent treatment modalities, may be applicable in future cases of this disease as dictated on a case-by-case basis. If surgery is ultimately pursued, overdistension of the urinary bladder should be avoided, or at least minimized as much as possible, so as to prevent the possibility of a vasovagal reaction.

Encrusted Uropathy: A Comprehensive Overview—To the Bottom of the Crust

Encrusted uropathy is a rare subacute to chronic inflammatory disorder caused by infection with urease-producing bacteria, mainly Corynebacterium urealyticum. The disorder is characterized by urothelial deposition of struvite and carbonated apatite, resulting in encrustations and ulceronecrotic inflammation of the urothelium and surrounding tissues. Most commonly, encrusted uropathy is encountered in patients with predisposing conditions. The disease remains underdiagnosed. High urinary pH and negative conventional urine cultures should raise suspicion of the diagnosis. Prognosis is dependent on timely diagnosis and treatment installment, which consists of urological removal of encrustations in combination with urinary acidification and long-term antibiotic therapy.

Antimicrobial Susceptibility and Characterization of Resistance Mechanisms of Corynebacterium urealyticum Clinical Isolates

Corynebacterium urealyticum is a non-diphtherial urease-producing clinically relevant corynebacterial, most frequently involved in urinary tract infections. Most of the C. urealyticum clinical isolates are frequently resistant to several antibiotics. We investigated the susceptibility of 40 C. urealyticum isolated in our institution during the period 2005–2017 to eight compounds representative of the main clinically relevant classes of antimicrobial agents. Antimicrobial susceptibility was determined by the Epsilometer test. Resistance genes were searched by PCR. All strains were susceptible to vancomycin whereas linezolid and rifampicin also showed good activity (MICs90 = 1 and 0.4 mg/L, respectively). Almost all isolates (39/40, 97.5%) were multidrug resistant. The highest resistance rate was observed for ampicillin (100%), followed by erythromycin (95%) and levofloxacin (95%). Ampicillin resistance was associated with the presence of the blaA gene, encoding a class A β-lactamase. The two rifampicin-resistant strains showed point mutations driving amino acid replacements in conserved residues of RNA polymerase subunit β (RpoB). Tetracycline resistance was due to an efflux-mediated mechanism. Thirty-nine PFGE patterns were identified among the 40 C. urealyticum, indicating that they were not clonally related, but producing sporadic infections. These findings raise the need of maintaining surveillance strategies among this multidrug resistant pathogen.

Preliminary In Vitro Studies on Corynebacterium urealyticum Pathogenetic Mechanisms, a Possible Candidate for Chronic Idiopathic Prostatitis?

Corynebacterium urealyticum is a well-known opportunistic uropathogen that can occur with cystitis, pyelonephritis, and urinary sepsis. Although a wide variety of coryneform bacteria have been found from the male genital tract of prostatitis patients, only one clinical case of prostatitis caused by C. urealyticum has been reported. The aim of this study was to evaluate the in vitro tropism of C. urealyticum towards LNCaP (lymph node carcinoma of the prostate) human cells line and the influence of acetohydroxamic acid as an irreversible urease inhibitor on different aspects of its pathogenicity by means of several in vitro tests, such as the determination and analysis of growth curves, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, the production of biofilms, and adhesion to LNCaP and HeLa cell lines. Results have brought new pieces of evidence on the in vitro tropism of C. urealyticum for the human prostate cell line LNCaP and the therapeutic use of the irreversible urease inhibitors such as acetohydroxamic acid (AHA), not only as enzyme blockers to facilitate the removal of encrustations but also as modulators of some pathogenic mechanisms. These interesting preliminary data allow us to assert that there is a real possibility that C. urealyticum is a new candidate for chronic idiopathic prostatitis.

Novel mutations in the QRDR region gyrA gene in multidrug-resistance Corynebacterium spp. isolates from intravenous sites

The resistance to fluoroquinolones in corynebacteria is due to mutations occurring in the quinolone-resistance-determining region (QRDR) of the gyrA gene encoding the enzyme gyrase A subunit. In recent years we can observe an increasing number of infections caused by multidrug-resistant Corynebacterium striatum, Corynebacterium jeikeium and Corynebacterium urealyticum, including wide range of disorders, such as invasive infections. In this study 14 Corynebacterium spp. isolated from intravenous sites were sequenced and new combinations of mutations in the QRDR of the gyrA gene were found in C. jeikeium and C. urealyticum. Nowadays, no study comparing mutations in this region and the susceptibility to fluoroquinolones in C. jeikeium and C. urealyticum has been described. All the isolates that showed double mutation (position 87 and 91) in the QRDR gyrA gene had high MIC to the fluoroquinolones tested.