Case Report: Subtherapeutic Vancomycin and Meropenem Concentrations due to Augmented Renal Clearance in a Patient With Intracranial Infection Caused by Streptococcus intermedius.

Streptococcus intermedius occasionally causes brain abscesses that can be life-threatening, requiring prompt antibiotic and neurosurgical treatment. The source is often dental, and it may spread to the eye or the brain parenchyma. We report the case of a 34-year-old man with signs of apical periodontitis, endophthalmitis, and multiple brain abscesses caused by Streptococcus intermedius. Initial treatment with meropenem and vancomycin was unsuccessful due to subtherapeutic concentrations, despite recommended dosages. Adequate concentrations could be reached only after increasing the dose of meropenem to 16 g/day and vancomycin to 1.5 g × 4. The patient exhibited high creatinine clearance consistent with augmented renal clearance, although iohexol and cystatin C clearances were normal. Plasma free vancomycin clearance followed that of creatinine. A one-day dose of trimethoprim-sulfamethoxazole led to an increase in serum creatinine and a decrease in both creatinine and urea clearances. These results indicate that increased tubular secretion of the drugs was the cause of suboptimal antibiotic treatment. The patient eventually recovered, but his left eye needed enucleation. Our case illustrates that augmented renal clearance can jeopardize the treatment of serious bacterial infections and that high doses of antibiotics are needed to achieve therapeutic concentrations in such cases. The mechanisms for regulation of kidney tubular transporters of creatinine, urea, vancomycin, and meropenem in critically ill patients are discussed.

The importance of correct estimation of renal function for drug treatment in hospitalized elderly patients, especially women: A prospective observational study
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AIM: To compare renal function by several GFR formulas (particularly cystatin C eGFR-"CAPA") in relation to renal risk drugs (RRDs) in patients admitted to two geriatric wards in a university geriatric department. MATERIALS AND METHODS: This was a prospective quality improvement study including 108 patients, 2/3 women, age ≥ 75 years, admitted with multimorbidity. Renal function tests were performed with Cockcroft & Gault with uncalibrated (C&Guc) and calibrated creatinine (C&Gcc), and 3 - 4 points' iohexol clearance (mGFR) in mL/min, and eGFR with MDRD4, CKD-EPI, CAPA, and BIS2 clearance in mL/min/1.73m2. Agreement was tested by Bland & Altman analysis. The number and type of RRDs were analyzed. RESULTS: Measured GFR, C&Gcc, and C&Guc were mean 37, 39, and 32 mL/min, respectively. Estimated GFR by MDRD4, CKD-EPI, CAPA, and BIS2 were mean 56, 52, 45, and 40 mL/min/1.73m2, respectively. Compared to mGFR, women had significantly higher clearance for all estimates except for C&Gcc and C&Guc. C&Gcc, C&Guc, and BIS2 showed the lowest bias. 38 RRDs were identified. 96 patients used a mean of 2.3 RRDs per patient, and 1.7 RRDs needed dose adjustments. Cardiovascular drugs and analgesics were the most frequent RRDs. DISCUSSION: The C&Gcc, C&Guc, and BIS2 equations gave the best estimate of kidney function in relation to mGFR for drug dosing in the elderly. The eGFR methods showed significantly higher clearance than mGFR, C&Gcc, C&Guc, and BIS2. RRDs that needed dose adjustment were common in this geriatric population. If the eGFR formulas (MDRD4, CKD-EPI, and CAPA) are used instead of C&Gcc, C&Guc, and BIS2, higher and potentially more risky doses of RRDs may be administered to geriatric patients over 75 years, women in particular.

Ganciclovir concentrations in the cerebral extracellular space after valganciclovir treatment; a case study.

Nearly all glioblastomas (GBMs), brain tumours with very poor prognosis, are infected with human cytomegalovirus (CMV). The anti-CMV drug valganciclovir (VGCV) has shown promise as a treatment option for patients with GBM, but its penetration into the central nervous system (CNS) is unknown. Here we describe a patient with GMB receiving VGCV in whom an intracerebral microdialysis catheter was implanted and ganciclovir (GCV) concentrations in brain extracellular fluid (BECF) and serum were monitored. GCV was rapidly absorbed. Cmax values (at 3 h) in serum and BECF were 19.6 and 10.2 µmol/L, T½ values were 3.2 and 4.5 h, and plasma and BECF AUC0-∞ values were 90.7 and 75.9 µmol h/L, respectively. Thus, VGCV treatment results in significant intracerebral levels of GCV that may be sufficient for therapeutic effects. Further studies of this drug in patients with GBM are warranted.

Adverse drug reactions and impaired renal function in elderly patients admitted to the emergency department: a retrospective study.

BACKGROUND: Adverse drug reactions (ADRs) are common in elderly patients. There are various reasons for this, including age- and disease-related alterations in pharmacokinetics and pharmacodynamics as well as the common practice of polypharmacy. The decline in renal function in elderly patients may also predispose them to pharmacological ADRs (type A, augmented). Patients receiving home healthcare may be at even higher risk. OBJECTIVES: To study ADRs as a cause of acute hospital admissions in a defined cohort of elderly patients (aged >or=65 years) registered to receive home healthcare services, with special reference to impaired renal function as a possible risk factor. METHODS: This was a retrospective study of 154 elderly patients aged >or=65 years admitted to the emergency department of a university hospital in Stockholm, Sweden, in October-November 2002. Estimated creatinine clearance (eCL(CR)) was calculated from the Cockcroft-Gault formula, and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation. ADRs were defined according to WHO criteria. All medications administered to patients at admission and at discharge were collated. These and other data were collected from computerized hospital records. RESULTS: ADRs were judged to contribute to or be the primary cause of hospitalization in 22 patients, i.e. 14% of 154 patients registered to receive home healthcare. Eleven of the 22 patients were women. All but one ADR were type A. Excessive doses or drugs unsuitable in renal insufficiency were present in seven patients in the ADR group compared with only four patients in the group without ADRs (p = 0.0001). Patients with ADRs did not differ significantly from those without ADRs in relation to age, plasma creatinine, eCL(CR), weight or number of drugs prescribed at admission. However, women with ADRs were significantly older than women without ADRs (mean +/- SD age 88.8 +/- 5.7 years vs 82.5 +/- 8.0 years, respectively; p = 0.014) and had significantly lower mean +/- SD eCL(CR) values (25.5 +/- 10.8 and 37.1 +/- 17.1 mL/min, respectively; p = 0.035). Median MDRD eGFR was significantly higher than median eCL(CR) (59 [range 6-172] mL/min/1.73 m2 vs 38 [range 5-117] mL/min, respectively; p = 0.0001). CONCLUSIONS: In elderly patients registered to receive home healthcare, 14% of hospital admissions were primarily caused by ADRs. One-third of these ADRs were related to impaired renal function, generally in very old women. These ADRs may be avoided by close monitoring of renal function and adjustments to pharmacotherapy (drug selection and dose), particularly in very elderly women.