Rapid Evolution of Multidrug Resistance in a Candida lusitaniae Infection during Micafungin Monotherapy.

Candida (Clavispora) lusitaniae is a rare, emerging non-albicans Candida species that can cause life-threatening invasive infections, spread within hospital settings, and rapidly acquire antifungal drug resistance, including multidrug resistance. The frequency and spectrum of mutations causing antifungal drug resistance in C. lusitaniae are poorly understood. Analyses of serial clinical isolates of any Candida species are uncommon and often analyze a limited number of samples collected over months of antifungal therapy with multiple drug classes, limiting the ability to understand relationships between drug classes and specific mutations. Here, we performed comparative genomic and phenotypic analysis of 20 serial C. lusitaniae bloodstream isolates collected daily from an individual patient treated with micafungin monotherapy during a single 11-day hospital admission. We identified isolates with decreased micafungin susceptibility 4 days after initiation of antifungal therapy and a single isolate with increased cross-resistance to micafungin and fluconazole, despite no history of azole therapy in this patient. Only 14 unique single nucleotide polymorphisms (SNPs) were identified between all 20 samples, including three different FKS1 alleles among isolates with decreased micafungin susceptibility and an ERG3 missense mutation found only in the isolate with increased cross-resistance to both micafungin and fluconazole. This is the first clinical evidence of an ERG3 mutation in C. lusitaniae that occurred during echinocandin monotherapy and is associated with cross-resistance to multiple drug classes. Overall, the evolution of multidrug resistance in C. lusitaniae is rapid and can emerge during treatment with only first-line antifungal therapy.

Treatment of traumatic cervical myelopathy with surgery, prolonged positive-pressure ventilation, and physical therapy in a dog.

CASE DESCRIPTION: A 9-year-old dog was evaluated for traumatic cervical myelopathy after a surgical attempt to realign and stabilize the C2 and C3 vertebrae. CLINICAL FINDINGS: The dog could not ventilate spontaneously and was tetraplegic; positive-pressure ventilation (PPV) was maintained. Myelography and computed tomography revealed spinal cord compression with subluxation of the C2 and C3 vertebrae and extrusion of the C2-3 intervertebral disk. TREATMENT AND OUTCOME: Surgically, the protruding disk material was removed and the vertebrae were realigned with screws and wire. For PPV, assist control ventilation in volume control mode and then in pressure control mode was used in the first 6 days; this was followed by synchronized intermittent mandatory ventilation until 33 days after the injury; then only continuous positive airway pressure was provided until the dog could breathe unassisted, 37 days after the injury. Physical therapy that included passive range of motion exercises, neuromuscular electrical stimulation, and functional weight-bearing positions was administered until the dog was discharged 46 days after injury; the dog was severely ataxic and tetraparetic but could walk. Therapy was continued at home, and 1 year later, the dog could run and had moderate ataxia and tetraparesis. CLINICAL RELEVANCE: Hypoventilation with tetraparesis in traumatic spinal cord injury can be successfully treated with PPV exceeding 30 days, surgery, and physical therapy.

Comparison of measured oxyhemoglobin saturation and oxygen content with analyzer-calculated values and hand-calculated values obtained in unsedated healthy dogs.

OBJECTIVE: To compare direct measurements of canine oxyhemoglobin (HbO2) saturation and blood oxygen content (ContO2) in healthy dogs with analyzer-calculated values derived by use of a human HbO2 relationship and with hand-calculated values derived by use of a canine HbO2 relationship. ANIMALS: 17 healthy dogs. PROCEDURE: 3-mL samples of heparinized arterial and jugular venous blood were collected from each dog. The pH, Pco2, Po2, hemoglobin, HbO2, carboxyhemoglobin, methemoglobin, and ContO2 were measured; HbO2 and ContO2 were calculated automatically by analyzers and also hand-calculated. Blood gas analyzer-calculated and hand-calculated HbO2 values were compared with co-oximeter-measured HbO2 values. Analyzer-calculated and hand-calculated ContO2 values were compared with oxygen content analyzer-measured values. RESULTS: Hand-calculated HbO2 values for arterial and jugular venous samples were slightly but significantly lower than those calculated by a blood gas analyzer or obtained from a co-oximeter. Hand-calculated and analyzer-calculated arterial and venous ContO2 were similar to measured values. CONCLUSIONS AND CLINICAL RELEVANCE: Although certain HbO2 and ContO2 values generated by use of the different methods were significantly different, these differences are unlikely to be clinically important in healthy dogs.