An 82 year old man came to the Emergency Department for: dyspnoea, increased expectoration and somnolence. Relevant personal history: hypertension, diabetes mellitus, paroxysmal atrial fibrillation, Guillen-Barré syndrome and oropharyngeal epidermoid carcinoma T3N0M0 with associated paraneoplastic syndrome of inadequate secretion of antidiuretic hormone (SIADH), pending the start of radical radiotherapy. His usual treatment consists of acetylsalicylic acid 100 mg, lorazepam 1 mg, silidosin 8 mg and omeprazole 20 mg, all taken once a day; (tolvaptan discontinued after the last admission).
The patient was diagnosed with bilo-bar pneumonia due to bronchoaspiration associated with hypoosmolar hyponatraemia (sodium: 101 meq/L (normal range (R.N.) 135-145 meq/L), Osmolality 210 mOsm/kg (R.N. 280-300 mOsm/kg). He presented with severe dysphagia and bleeding associated with pharyngeal tumour, planning gastrostomy and initiating parenteral nutrition via peripheral route, empirical antibiotic treatment with meropenem 1000 mg/8 h and natraemia replacement by serum therapy (252 meq of sodium in 500 mL of 0.9% physiological saline solution every 12 hours); he had normal renal function (MDRD-4 IDMS: > 60 ml/min/1.73m2).
On admission to Internal Medicine, clinical and analytical improvement was observed (sodium: 130 meq/L), and the Nephrology Department assessed paraneoplastic SIADH with good response to natraemic replacement by means of serum therapy, which was suspended. Treatment was restarted at low doses of tolvaptan to avoid overcorrection (7.5 mg/24 h) and subsequently increased to the usual dose of 15 mg/24 h. The patient presented with febrile syndrome without a clear focus, and empirical treatment was started with cefepime 2000 mg/12 h, vancomycin 1000 mg/12 h and oseltamivir 75 mg/12 h. Blood cultures were requested, and the results were positive. Blood cultures were requested and were positive for methicillin-resistant Streptococcus epidermidis, sensitive to vancomycin (MIC = 2 mg/L), so antibiotic treatment was maintained, considering bacteraemia due to catheter, which was withdrawn. A transthoracic echocardiogram was performed, ruling out endocarditis. Subsequent blood cultures were negative.
Three days after starting treatment, the dose of vancomycin was increased to 1250 mg/12 h due to persistent febrile peaks, CRP: 9.6 mg/dL (R.N: 0.0-0.5 mg/dL) and procalcitonin: 4.01 mcg/L (R.N: 0.0-0.5 mcg/L). After two days, new plasma concentrations were extracted and were still lower (8.4 μg/mL) (the possibility of error in the extraction of the sample or in the accuracy and precision of the measurement was assessed), so a pharmacokinetic study was performed to predict the dose by Bayesian estimation, using the PKS® programme (Abbott Base Pharmacokinetic System, Abbott Diagnostics), calculating a t1/2 of 6.4 h and increasing the dose to 1000 mg/8 h.
Oral metronidazole 500 mg/8 h was added to the treatment due to persistent Clostridium difficile diarrhoea, and two days later, worsening renal function was observed due to digestive losses, causing pre-renal failure with hyponatraemia (sodium: 115 meq/L), which preceded the elevation of creatinine levels to 2.46 mg/dL and elevation of pre-dose plasma concentrations of vancomycin to 43.1 μg/mL, for which treatment was discontinued. Acute renal failure develops and creatinine values of 5.07 mg/dL are reached in the days following discontinuation of intravenous vancomycin treatment. Nine days after discontinuation, elimination remains very slow, with a t1/2 of 132 h and reaching a plasma concentration of 25.5 μg/mL. Concentrations below the therapeutic range are not reached until 15 days after discontinuation of antibiotic treatment.
The Nephrology Department suspended enteral nutrition to avoid promoting diarrhoea, and performed a new natraemic correction by suspending treatment with tolvaptan, increasing serum therapy and forcing diuresis (approximately 3000 mL/day) to eliminate plasma vancomycin. Vancomycin was administered via gastrostomy due to persistent Clostridium difficile diarrhoea despite treatment with oral metronidazole. Subsequently, the patient presented hypertension, with very abundant diuresis and very positive free water producing hypernatraemia (sodium: 157 meq/L) despite suspension of tolvaptan, so saline solutions were reduced to increase free water. He also presented metabolic acidosis, which was corrected with bicarbonate, and respiratory alkalosis, and a chest X-ray was performed due to suspected left pleural effusion. Due to persistent high plasma concentrations of vancomycin and hypernatremia, serum therapy was readjusted and desmopressin was added.
Finally, resolution of the bacteraemia associated with methicillin-resistant Streptococcus epidermidis, normal haematological formula and afebrile after resolution of the vancomycin intoxication, gradual resolution of the episode of diarrhoea, recovery of renal function and natraemia, reintroduction of enteral diet by gastrostomy and radiotherapy (36 sessions), discontinuation of metronidazole and oral vancomycin.