Continuous vancomycin has been previously reported to maximize antimicrobial activity while avoiding toxicities associated with dose escalation, but the efficacy of this dosing strategy has not been reported. This case report describes the successful use of continuous vancomycin, including improvement in lung function and avoidance of nephrotoxicity, demonstrated in a pediatric cystic fibrosis (CF) patient with MRSA

Esther, Charles R.

McKinzie, Cameron J.

Vece, Timothy J.

English

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Received: 15 May 2017 | Accepted: 15 May 2017DOI: 10.1002/ppul.23844CASE REPORTContinuous vancomycin in a pediatric cystic fibrosis patientCameron J. McKinzie PharmD, BCPPS, BCPS CPP1 |Charles R. Esther MD, PhD2 | Timothy J. Vece MD21Department of Pharmacy, University ofNorth Carolina Medical Center, Chapel Hill,North Carolina2Division of Pediatric Pulmonology,Department of Pediatrics, University of NorthCarolina School of Medicine, Chapel Hill,North CarolinaCorrespondenceCameron J. McKinzie, PharmD, BCPPS, BCPS,CPP, Department of Pharmacy, University ofNorth Carolina Medical Center, 101 ManningDrive, CB 7600, Chapel Hill 27516, NC.Email: cameron.mckinzie@unchealth.unc.eduAbstractContinuous vancomycin has been previously reported to maximize antimicrobialactivity while avoiding toxicities associated with dose escalation, but the efficacy ofthis dosing strategy has not been reported. This case report describes the successfuluse of continuous vancomycin, including improvement in lung function and avoidanceof nephrotoxicity, demonstrated in a pediatric cystic fibrosis (CF) patient with MRSA.K E YWORD Scystic fibrosis, MRSA, vancomycin1 | BACKGROUNDVancomycin is a glycopeptide antibiotic that is effective against gram-positive organisms, including methicillin-resistant Staphylococcus aureus(MRSA). Based on its time-dependent antimicrobial activity, maximalbactericidal effects occur when the concentration of vancomycin remainssignificantly above the bacterial minimum inhibitory concentration (MIC).However, targeting higher peak concentrations to maximize time aboveMIC is associated with more adverse effects, such as nephrotoxicity.Continuous vancomycin therapy has been previously reported tomaximizethe antimicrobial effects of vancomycin while avoiding the toxicitiesassociatedwithdoseescalationandelevatedpeakconcentrations, althoughthe efficacy of this approach was not reported.1 Here we describe thesuccessful use of continuous vancomycin in a pediatric cystic fibrosis (CF)patient with MRSA who had a significant drug allergy profile.2 | CASEA 12-year-old girl with CF was admitted to the inpatient pediatricpulmonary service for treatment of a CF pulmonary exacerbation.Her pulmonary function tests (PFTs) on admission were percentpredicted (pp) FVC 81, ppFEV1 79%, ppFEF25-75 77%, as comparedto her best PFTs in the past year of ppFVC 110, ppFEV1 105, andppFEF25-75 100. Since presenting to our CF center one and a halfyears prior, the patient has had three bronchoscopy cultures and 12sputum cultures obtained. Of these, two bronchoscopies werepositive for MRSA only, and the third grew MRSA and mold. Of thesputum cultures, eight grew only MRSA, and another (the firstobtained at our center) grew Pseudomonas in addition to MRSA.Given thishistoryof infectionprimarilywithMRSA,prior toadmissionshe was treated with a 3 week course of tedizolid directed against MRSAas her typical respiratory pathogen. On week prior to admission oralminocycline was added to her antibiotic regimen. She underwentbronchoscopy upon admission to determine if there were any otherpathogens present that could account for her failure to respond totedizolid, but cultures only grew 800 000CFU/mL of MRSA. The patienthas multiple allergies and reactions to medications that complicatedantibiotic management, including significant hives with both minocyclineand ceftaroline, independent of one another; facial swelling withaztreonam; paresthesias with linezolid during two treatment courses;andsignificant redmansyndromewith intermittentdosingofvancomycin.Hermost recent culture susceptibilities indicatedsensitivity toceftaroline,doxycycline, linezolid, and vancomycin (with a MIC of 2mcg/mL) andresistance to clindamycin and sulfamethoxazole/trimethoprim.Upon admission she was started on IV minocycline, however, shedeveloped hives. The pediatric allergy service was consulted and theydetermined that she was having a delayed hypersensitivity reaction tominocycline, therefore it was discontinued. Given this patient's numerousdrug allergies and reactions, the decision was made to treat her pulmonaryexacerbation with vancomycin, utilizing a longer infusion time of 2 h andpremedication with diphenhydramine 25mg to minimize reaction. Despitethese interventions, thepatientcontinuedtoexperience intolerable redmansymptoms, which did not resolve by increasing the infusion time to 3h anddiphenhydramine dose to 50mg. After 3 days, she was started oncontinuous vancomycin, with a goal concentration of 20-25mcg/mL. TheE4 | © 2017 Wiley Periodicals, Inc. wileyonlinelibrary.com/journal/ppul Pediatric Pulmonology. 2018;53:E4–E5.patient was initiated on 3000mg over 24h (64mg/kg), and a level wasobtained the followingmorning, about 22.5 h after the start of the infusion(Table 1). The patient remained in the hospital for five additional days afterstarting the continuous vancomycin, during which time one doseadjustment was made (Table 1). Prior to discharge, her repeat PFTsdemonstrated significant improvement in her lung function to ppFEV1 103.She was discharged home, where she completed an additional 5 days ofcontinuous vancomycin before discontinuing vancomycin due to develop-ment of hives on her lower extremities. No changes in renal function wereobserved, and the patient felt that the redman symptoms she experiencedwere tolerable with diphenhydramine 25mg as needed.3 | DISCUSSIONThe evidence supporting the use of continuous vancomycin is limited. Themajority of studies evaluating continuous vancomycin are in adult patients,andmostevaluatenephrotoxicityandadverseeffects, asopposed toclinicalefficacy, as the primary endpoint.2–3 These previous studies havedemonstrated that continuous vancomycin does not result in an increasedincidence of nephrotoxicity, and in some studies, the incidence wassignificantly less when compared to intermittent vancomycin.In2012,McKamyetal,1 describedadosingguideline that convertedpediatric patients at a single institution from intermittent vancomycindosing to continuous vancomycin for patientswho had two consecutivesubtherapeutic trough concentrations. Patients had to have eitherpneumonia or osteomyelitis due to gram-positive organisms, includingMRSA. The authors found fewadverse effects associatedwhenpatientswere transitioned to continuous vancomycin, including nephrotoxicity.This study did not report patient outcomes.In our patient, it is interesting to note that she toleratedcontinuous vancomycin despite her significant red man syndromewith intermittent dosing. Given that red man syndrome is typicallyassociated with rapid infusion of vancomycin, it is reasonable toconsider that the slower continuous infusion may be more tolerable.4Our patient's case demonstrates successful use of continuousvancomycin in a pediatric CF patient with significant drug allergies relatedto antimicrobials targeting her MRSA, as well as resistance limitingtherapeutic options. In addition to achieving therapeutic vancomycinconcentrations from the beginning of therapy, our patient also had nonephrotoxicity, as assessed by serum creatinine, associated with thecontinuous vancomycin and had a significant improvement in PFTs,demonstrating efficacy of this dosing regimen.CONFLICTS OF INTERESTThe views expressed in this article do not communicate an officialposition of the University of North Carolina Medical Center orUniversity of North Carolina School of Medicine.ORCIDCameron J. McKinzie http://orcid.org/0000-0003-1401-5628Charles R. Esther http://orcid.org/0000-0002-8081-2986REFERENCES1. McKamy S, Chen T, Lee M, Ambrose PJ. Evaluation of a pediatriccontinuous-infusion vancomycin guideline. Am J Health-Syst Pharm.2012;69:2066–2071.2. Man SSK, Carr RR, Ensom MHH. Comparison of continuous andintermittent IV infusion of vancomycin: systematic review. Can J HospPharm. 2010;63: 373–381.3. DiMondi VP, Rafferty K. Review of continuous-infusion vancomycin.Ann Pharmacother. 2013;47:219–227.4. Wallace MR, Mascola JR, Oldfield EC. Red man syndrome: incidence,aetiology and prophylaxis. J Infect Dis. 1991;164:1180–1185.How to cite this article: McKinzie CJ, Esther CR, Vece TJ.Continuous vancomycin in a pediatric cystic fibrosis patient.Pediatric Pulmonology. 2018;53:E4–E5.https://doi.org/10.1002/ppul.23844TABLE 1 Laboratory values and clinical decision makingDay BUN (mg/dL) SCr (mg/dL)Vancomycinconcentration (μg/mL) Action taken1 10 0.42 - -8 11 0.45 25.4 Continued same dose9 - - 27.7 Decreased dose to 2500mg/day(53mg/kg)10 10 0.46 21.8 Continued same dose11 8 0.46 23.2 Continued same dose14a 10 0.45 - -15a - - 22.3 Continued same doseaThese labs were obtained while the patient was outpatient.MCKINZIE ET AL. | E5

Continuous vancomycin in a pediatric cystic fibrosis patient

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Continuous vancomycin in a pediatric cystic fibrosis patient

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