Rapid onset vancomycin-induced thrombocytopenia confirmed by vancomycin antibody test

We report a case of vancomycin-induced thrombocytopenia (VIT) with rapid onset after re-exposure to vancomycin. A 58-year-old man with cellulitis was initiated on vancomycin. Approximately 1 hour into the vancomycin infusion, the patient developed an infusion-related reaction. Vancomycin infusion was stopped. A complete blood count obtained 4 hours after discontinuation of the vancomycin infusion revealed a platelet count of 31 ×10­9/L. Investigations ruled out likely causes of thrombocytopenia. VIT was diagnosed based on clinical symptoms and confirmed with drug-dependent platelet antibody testing. Without complications, platelet counts recovered within 7 days after discontinuation of vancomycin. No correlation between vancomycin level and VIT was observed.

Assessment of Empiric Vancomycin Regimen in the Neonatal Intensive Care Unit

<p><strong>ABSTRACT</strong><br /><strong></strong></p><p><strong>Background:</strong> Vancomycin is used to treat serious gram-positive infections in neonates. Currently, there is no consensus on the preferred empiric dosing regimen or target trough vancomycin levels for neonates. The current Fraser Health empiric dosing regimen, implemented in 2010, was designed to achieve target trough levels of 5 to 15 mg/L. <br /><strong></strong></p><p><strong>Objectives:</strong> To determine the percentage of neonates receiving vancomycin in whom target trough levels of 5 to 15 mg/L were achieved, to identify the times to negative culture result and clinical resolution, and to determine the incidence of nephrotoxicity.<br /><strong></strong></p><p><strong>Methods:</strong> A chart review was completed for patients who had received vancomycin in the neonatal intensive care unit of either Surrey Memorial Hospital or Royal Columbian Hospital from June 2012 to May 2017 and for whom at least 1 interpretable vancomycin level was available. <br /><strong></strong></p><p><strong>Results:</strong> A total of 87 vancomycin encounters (in 78 neonates) were identified in which the drug had been given according to the Fraser Health empiric dosing regimen. Target trough vancomycin level (5 to 15 mg/L) was achieved in 75% of these encounters. The mean times to negative culture result and clinical resolution were 5 and 6 days, respectively. There was no statistically significant correlation between vancomycin level <br />and time to clinical resolution (rs = 0.366, p = 0.072). Among cases in which the trough vancomycin level exceeded 15 mg/L, the incidence of<br />nephrotoxicity was 22% (4/18). <br /><strong></strong></p><p><strong>Conclusions:</strong> The current Fraser Health empiric dosing regimen for vancomycin achieved target trough levels of the drug for most neonates in this study. Targeting trough levels less than 15 mg/L when appropriate to the infection type may limit nephrotoxicity associated with vancomycin in neonates. Further studies are needed to evaluate the clinical significance of various vancomycin levels.</p><p><strong>RÉSUMÉ</strong><br /><strong></strong></p><p><strong>Contexte :</strong> La vancomycine est utilisée dans le traitement d’infections graves à bactéries à Gram positif chez le nouveau-né. Il n’y a pour l’instant pas de consensus quant à la posologie empirique ou aux concentrations minimales visées de vancomycine à privilégier chez le nouveau-né. La posologie empirique actuelle de la Fraser Health, instaurée en 2010, visait des concentrations minimales de 5 à 15 mg/L. <br /><strong></strong></p><p><strong>Objectifs :</strong> Déterminer le pourcentage de nouveau-nés ayant reçu les concentrations minimales visées de 5 à 15 mg/L de vancomycine, établir le temps nécessaire à l’obtention d’un résultat de culture négatif et celui nécessaire à la disparition clinique des symptômes et déterminer l’incidence de la néphrotoxicité.</p><p><strong>Méthodes :</strong> Les investigateurs ont analysé des dossiers de patients ayant reçu de la vancomycine pendant leur séjour à l’unité de soins intensifs néonatals du Surrey Memorial Hospital ou du Royal Columbian Hospital entre juin 2012 et mai 2017, qui mentionnaient au moins une concentration de vancomycine interprétable. <br /><strong></strong></p><p><strong>Résultats :</strong> Ils ont répertorié 87 traitements de vancomycine (chez 78 nouveau-nés) administrés selon la posologie empirique de la Fraser Health. Les concentrations minimales visées de 5 à 15 mg/L ont été atteintes dans 75 % de ces traitements. Le temps moyen nécessaire à l’obtention d’un résultat de culture négatif ou à la disparition clinique des symptômes était respectivement de cinq et de six jours. Aucune corrélation statistiquement significative entre les concentrations de vancomycine et le temps nécessaire à la disparition clinique des symptômes n’a été relevée (rs = 0,366, p = 0,072). Parmi les cas où les concentrations minimales de vancomycine dépassaient 15 mg/L, l’incidence de néphrotoxicité était de 22 % (4/18). <br /><strong></strong></p><p><strong>Conclusions :</strong> La posologie empirique de vancomycine actuellement en place à la Fraser Health a permis d’atteindre les concentrations minimales visées de médicament pour la plupart des nouveau-nés de la présente étude. Cibler des concentrations minimales de moins de 15 mg/L lorsque cela est pertinent en fonction du type d’infection pourrait limiter le nombre de cas de néphrotoxicité associés à la vancomycine chez les nouveau-nés. De plus amples études sont nécessaires pour évaluer la portée clinique de différentes concentrations de vancomycine.</p>

An Unusual Case of Ototoxicity with Use of Oral Vancomycin

Introduction. Systemic absorption of oral vancomycin is poor due to the size of the molecule and its pharmacokinetics. It has an elimination half life of 5–11 hours in patients with normal renal function. We present a rare case of ototoxicity after oral vancomycin administration and detectable serum vancomycin levels 24 hours after cessation of vancomycin. Case Presentation. A 42-year-old woman with a history of hypertension, diabetes mellitus, and previously treated Clostridium difficile colitis presented with abdominal pain and diarrhea for two weeks. Clostridium difficile infection was confirmed by PCR, and at the time of diagnosis and initiation of therapy, the patient had normal renal function. Vancomycin was initiated at a dose of 125 mg po q6h. After the third dose of oral vancomycin, the patient reported new symptoms of lightheadedness, sensations of “buzzing” and whistling of bilateral ears, and decreased perception of hearing described as “clogged ears.” The patient reported to the emergency department the next day due to worsening of these symptoms, and vancomycin dosing was reduced to every 8 hours; however, the patient reported the auditory symptoms persisted. On day three, vancomycin was discontinued with gradual resolution of symptoms over the next 12 hours. On day four, a serum random vancomycin level obtained 24 hours after the last dose was detectable at 2 mcg/dl. Temporal association of the patient’s symptoms and improvement with cessation of therapy along with a detectable vancomycin level indicates systemic absorption of oral vancomycin with subsequent ototoxicity. Discussion. The potential for absorption of oral vancomycin is not well described and is attributed to compromised intestinal epithelium allowing for increased drug absorption. Few studies suggested that oral vancomycin may result in therapeutic or even potentially toxic levels of serum vancomycin in patients with impaired renal function. Ototoxicity may be a transient or permanent side effect of vancomycin therapy and is related to high serum levels. Symptoms usually resolve after decreasing the dose or cessation of vancomycin. No detectable serum vancomycin levels were found in 98% of the patients treated with oral vancomycin in a prospective study. The described case is unusual because despite normal renal function, the patient still developed ototoxicity, and systemic absorption of the drug was confirmed with a measurable vancomycin level approximately 24 hours after the drug was stopped. Additionally, the only other medication prescribed to the patient at the time of vancomycin administration was metformin at a dose of 500 mg po bid which has no known idiosyncratic interactions potentiating adverse side effects to vancomycin. This case reflects that some patients may be more susceptible to increased systemic absorption via the oral route, and the possibility for ototoxicity should be considered and discussed with patients while prescribing oral vancomycin.

A Novel Vancomycin Standardized Calculations Method Achieved Therapeutic Trough Goals in Obese and Non-obese Patients in a Veterans Affairs Health Care System

Background Pharmacokinetic dosing of vancomycin in obese patients has not been standardized. Limited literature is available on appropriate dosing of vancomycin in this increasing population. We evaluated the utilization and impact of a standardized calculation method (SCM) in obtaining therapeutic vancomycin levels. Methods A SCM, including the use of an adjusted body weight for dosing and volume of distribution in obese patients, was implemented at our institution April 2014. Retrospective medical records review of hospitalized patients with a vancomycin steady-state trough level pre- (February 2013 to March 2014) and post-implementation (June 2014 to July 2015) of the SCM. Patients with dialysis, paraplegia/quadriplegia, vancomycin level drawn &lt; 48 hours of admit, trough level drawn &gt; 2 hours prior to next dose, during or after vancomycin infusion were excluded. Appropriateness of vancomycin levels were evaluated between the pre- (PreG) and post-groups (PostG), as well as BMI classification. Nephrotoxicity was defined as a rise in serum creatinine &gt; 0.5 mg/dl or &gt; 50% from baseline during or up to 72 hours after stopping vancomycin therapy. Appropriate statistical tests were analyzed using SPSS-PC (ver. 24, Chicago, IL). Results There were no significant differences in the PreG (n = 97) and PostG (n = 97) for age, gender, length of vancomycin therapy, and non-obese and obese patients. In the PostG, significant improvement in the overall use of the SCM (P &lt; 0.001) was determined. Other significant (P &lt; 0.001) factors associated with vancomycin patient management in the PostG were found. There was an overall significant improvement in achieving a therapeutic trough goal of 10–20 (±1 mcg/ml) in BMI classes, predominantly in BMI Class 4 PreG 26% and PostG 74%, P &lt; 0.05. More patients in the PreG (11) had the first trough &gt;21 mcg/ml than the PostG, (4), P = 0.104. Patients who developed nephrotoxicity included PreG 15% and 0% PostG, P = 0.115. Conclusion SCM of vancomycin regimens resulted in a significant improvement in obtaining therapeutic trough levels overall, including the obese BMI class 4. Defined nephrotoxicity was absent in the PostG group. Disclosures All authors: No reported disclosures.

The Role of Monitoring Vancomycin Levels in Patients with Peritoneal Dialysis-Associated Peritonitis

BackgroundThere is limited available evidence regarding the role of monitoring serum vancomycin concentrations during treatment of peritoneal dialysis (PD)-associated peritonitis.MethodsA total of 150 PD patients experiencing 256 episodes of either gram-positive or culture-negative peritonitis were included to investigate the relationship between measured serum vancomycin within the first week and clinical outcomes of cure, relapse, repeat or recurrence of peritonitis, catheter removal, temporary or permanent transfer to hemodialysis, hospitalization and death.ResultsVancomycin was used as an initial empiric antibiotic in 54 gram-positive or culture-negative peritonitis episodes among 34 patients. The median number of serum vancomycin level measurements in the first week was 3 (interquartile range; IQR 1 - 4). The mean day-2 vancomycin level, measured in 34 (63%) episodes, was 17.5 ± 5.2 mg/L. Hospitalized patients were more likely to have serum vancomycin levels measured on day 2 and ≥ 3 measurements in the first week. The peritonitis cure rates were similar between patients with < 3 and ≥ 3 measurements in the first week (77% vs 57%, p = 0.12) and if day-2 vancomycin levels were measured or not (68% vs 65%, p = 0.84). The average day-2 (18.0 ± 5.9 vs 16.6 ± 3.2, p = 0.5), first-week average (18.6 ± 5.1 vs 18.6 ± 4.3, p = 0.9) and nadir (14.5 ± 4.1 vs 13.6 ± 4.2, p = 0.5) vancomycin levels were comparable in patients who did or did not achieve peritonitis cure. Similar results were observed for all other clinical outcomes.ConclusionThe clinical outcomes of gram-positive and culture-negative peritonitis episodes are not associated with either the frequency or levels of serum vancomycin measurements in the first week of treatment when vancomycin is dosed according to International Society for Peritoneal Dialysis (ISPD) Guidelines.