Successful Long-Term Treatment of Cerebral Nocardiosis with Unexpectedly Low Doses of Linezolid in an Immunocompromised Patient Receiving Complex Polytherapy

Abstract

Cerebral nocardiosis is a severe infection that carries the highest mortality rate among all bacterial cerebral abscesses. We report on a case in an immunocompromised patient which was successfully treated with unexpectedly low doses of linezolid. Therapeutic drug monitoring was very helpful in highlighting issues of poor compliance and of drug-drug interactions. N ocardiosis is a rare but severe infectious disease which usually affects patients with deficient cell-mediated immunity (1). Although the primary site of infection is usually the lung, general dissemination with secondary involvement of the central nervous system (CNS) may sometimes occur (11), with abscess formation as a sign of microorganism tissue indwelling. The first-line treatment of CNS nocardiosis is trimethoprim-sulfamethoxazole, even for up to 1 year, but antibiotic discontinuation due to a high incidence of adverse drug reactions or to breakthrough resistance to sulfonamides is frequently needed (1). In these cases, neurosurgery to save the patient's life is often unavoidable, sometimes with relevant sequelae (11).Linezolid, an oxazolidinone with time-dependent activity, has proved effective for the treatment of Nocardia infections, even in the presence of cerebral dissemination (9). Although no dosage adjustment in the presence of renal or hepatic failure is required, in the last few years, it has been reported that some drug-drug interactions may alter its pharmacokinetic behavior, so that therapeutic drug monitoring (TDM) for optimization of drug exposure has been advocated (13). This may be especially useful in prolonged antimicrobial courses when drug-related adverse events like anemia, thrombocytopenia, and lactic acidosis may raise concerns (16).Here we describe a case of cerebral nocardiosis successfully treated for a long time with unexpectedly low doses of linezolid in a patient receiving complex polytherapy.A 67-year-old woman was diagnosed with cavitary pneumonia while undergoing treatment with cyclosporine plus prednisone because of cold agglutinin haemolytic anemia. After 3 weeks of wide-spectrum antibiotic therapy (with piperacillin-tazobactam plus vancomycin) with no radiological or clinical response and because of negative bronchoalveolar lavage fluid cultures, Aspergillus pneumonia was suspected and treatment with voriconazole was started. At that time, a diagnostic workup confirmed that no other body site was involved in any infective process.Approximately 1 month later, while on antimicrobial treatment, she was admitted to the emergency department because of aphasia and confusion, and while being examined, she experienced an epileptic seizure which resolved spontaneously. Brain computed tomography imaging revealed a single left posterior temporo-parietal plurinodular abscess with a perilesional edematous area, which was subsequently confirmed by nuclear magnetic resonance (NMR) imaging (Fig. 1A). A stereotactic brain biopsy of the aforementioned lesion allowed the identification of modified acid-fast variable branching f...

A 1 year retrospective audit of quality indicators of clinical pharmacological advice for personalized linezolid dosing: one stone for two birds?

“…Moreover, it must be recognized that the proposed therapeutic range for linezolid C min was not validated against atypical pathogens and Nocardia . However, favourable clinical outcome in a patient with cerebral nocardiosis was previously reported with this strategy by our group . Lastly, we did not consider in the cost balance analysis other potential sources for additional costs, such as those related to the time for CPA elaboration by the clinical pharmacologist or that related to the pharmacist's time for making the required dose adjustments for the intravenous route.…”

A 10‐Year Experience of Therapeutic Drug Monitoring (TDM) of Linezolid in a Hospital‐wide Population of Patients Receiving Conventional Dosing: Is there Enough Evidence for Suggesting TDM in the Majority of Patients?

“…While waiting for a better definition of the leading causes of the linezolid variability, these data should further strengthen the conviction that TDM might be a great opportunity for personalizing linezolid therapy in the majority of patients. This could be especially valuable in preventing toxicity among patients who are experiencing drug overexposure and in preventing therapeutic failure among patients who are experiencing drug underexposure . TDM might be of utmost importance for preventing drug‐related toxicity during long‐term treatment with linezolid, as, for example, for prosthetic and/or bone and joint infections and/or for MDR tuberculosis .…”

How do we use therapeutic drug monitoring to improve outcomes from severe infections in critically ill patients?

“…Consequently standard doses may result in a variable pharmacodynamic exposure [ 122 ], and are reported in the critically ill population with burns injuries [ 123 , 124 ]. Elevated plasma concentration and associated risk of toxicity have also been reported [ 125 – 127 ]. In general, data to date indicates that TDM may be required in about 30 to 40% of patients to avoid dose-dependent toxicity as well as therapeutic failure [ 24 , 122 ].…”