BEUDAMED
    FDA Adverse Event Injury Summary report: N

    INFUSION PUMP

    MDR report key: 4891857 · Received July 6, 2015

    Report

    Report Number
    3007566237-2015-01867
    Event Type
    Injury
    Date Received
    July 6, 2015
    Report Date
    June 20, 2015
    Manufacturer
    MEDTRONIC NEUROMODULATION
    Product Code
    LKK
    PMA / PMN Number
    P860004
    Adverse Event
    Yes
    Product Problem
    Yes
    Report Source
    Manufacturer report
    Reporter Location
    IN, US
    Reporter Occupation
    PHARMACIST

    Narratives

    Additional Manufacturer Narrative · 1

    (B)(4).

    Additional Manufacturer Narrative · 1

    IT WAS NOT POSSIBLE TO MATCH THIS EVENT WITH ANY PREVIOUSLY REPORTED EVENT. CONCOMITANT MEDICAL PRODUCTS: PRODUCT ID NEU_UNKNOWN_CATH, LOT# UNKNOWN, PRODUCT TYPE: CATHETER. (B)(4).

    Description of Event or Problem · 1

    NICHOLS, K.R., KNODERER, C.A., JACKSON, N.G., MANALOOR, J.J., CHRISTENSON, J.C. SUCCESS WITH EXTENDED-INFUSION MEROPENEM AFTER RECURRENCE OF BACLOFEN PUMP-RELATED ACHROMOBACTER XYLOSOXIDANS MENINGITIS IN AN ADOLESCENT. JOURNAL OF PHARMACY PRACTICE. 2015; 1-4 DOI: 10.1177/0897190015585757. SUMMARY: A (B)(6) FEMALE EXPERIENCED A RECURRENCE OF BACLOFEN PUMP-RELATED CENTRAL NERVOUS SYSTEM (CNS) INFECTION CAUSED BY ACHROMOBACTER, DESPITE ABSENCE OF RETAINED FOREIGN MATERIAL. DUE TO THE FAILURE OF MEROPENEM (120 MG/KG/D IN DIVIDED DOSES EVERY 8 HOURS AND INFUSED OVER 30 MINUTES) IN THE INITIAL INFECTION, THE DOSE WAS INFUSED OVER 4 HOURS DURING THE RECURRENCE. MEROPENEM IS ANTIBIOTIC FOR WHICH EFFICACY IS TIME DEPENDENT, AND 4-HOUR VERSUS 30-MINUTE INFUSIONS HAVE BEEN SHOWN TO PROLONG THE TIME THE CONCENTRATION OF THE ANTIBIOTIC EXCEEDS THE MINIMUM INHIBITORY CONCENTRATION (MIC) OF THE ORGANISM AT THE SITE OF INFECTION (T>MIC). MEROPENEM SERUM CONCENTRATIONS WERE OBTAINED AND INDICATED THAT T>MIC WAS AT LEAST 75% OF THE DOSING INTERVAL. OUR PATIENT IMPROVED WITH NO NOTED RECURRENCES OR ADVERSE EFFECTS ON THE EXTENDED-INFUSION MEROPENEM REGIMEN. UTILIZATION OF EXTENDED-INFUSION BETA-LACTAM DOSING WHENEVER POSSIBLE IN THE TREATMENT OF SERIOUS INFECTIONS CAUSED BY GRAM-NEGATIVE ORGANISMS SHOULD BE CONSIDERED, AS THIS DOSING APPEARS TO BE SAFE AND IMPROVES THE PROBABILITY OF ACHIEVING PHARMACOKINETIC/PHARMACODYNAMIC GOALS. REPORTED EVENT: A (B)(6) CAUCASIAN FEMALE RECEIVING INTRATHECAL BACLOFEN THERAPY FOR CEREBRAL PALSY-ASSOCIATED SPASTICITY WAS ADMITTED FOR BACLOFEN PUMP REVISION WHEN PART OF THE CATHETER WAS VISUALIZED EXTERIORLY WITH BREAKDOWN AT THE SITE OF CATHETER INSERTION INTO THE SPINE. CEREBROSPINAL FLUID (CSF) AND FLUID FROM THE BACLOFEN PUMP DEVICE INSERTION SITE WERE SENT FOR CULTURE DURING REPLACEMENT OF THE MALFUNCTIONING CATHETER. EMPIRIC THERAPY WITH GENTAMICIN (192 MG [7 MG/KG] INTRAVENOUSLY [IV] EVERY 24 HOURS] AND CEFEPIME (1370 MG [50 MG/KG] IV EVERY 8 HOURS, INFUSED OVER 4 HOURS) WAS INITIATED WHEN THE CEREBROSPINAL FLUID (CSF) GRAM STAIN INDICATED THE PRESENCE OF GRAM-NEGATIVE RODS. CULTURE AND SUSCEPTIBILITIES ARE ILLUSTRATED IN TABLE 1, AND IN CONSIDERATION WITH CLINICAL FINDINGS CONFIRMED A. XYLOSOXIDANS-ASSOCIATED BACLOFEN PUMP DEVICE POCKET INFECTION AND MENINGITIS. THE DEVICE AND ALL CATHETERS WERE SUBSEQUENTLY REMOVED, AND THE ANTIMICROBIAL THERAPY WAS CHANGED BASED ON THE SUSCEPTIBILITY FINDINGS TO MEROPENEM 1100 MG (40 MG/KG) IV EVERY 8 HOURS, INFUSED OVER 30 MINUTES. THE PATIENT COMPLETED 21 DAYS OF MEROPENEM THERAPY AT HOME VIA A PERIPHERALLY INSERTED CENTRAL CATHETER (PICC). AT A FOLLOW-UP APPOINTMENT 7 DAYS AFTER COMPLETION OF THERAPY, THE PATIENT WAS NOTED TO BE WELL AND EXHIBITING NO SIGNS OF INFECTION. APPROXIMATELY 5 MONTHS LATER, THE PATIENT PRESENTED TO THE EMERGENCY DEPARTMENT (ED) WITH COMPLAINTS OF PROGRESSIVE SLEEPINESS OVER THE PREVIOUS MONTH, WITH ACUTE UNRESPONSIVENESS AND ALTERED MENTAL STATUS. COMPUTED TOMOGRAPHY DEMONSTRATED HYDROCEPHALUS, AN EXTERNAL VENTRICULAR DRAIN (EVD) WAS INSERTED, AND BLOOD AND CSF CULTURES WERE SENT FOR ANALYSIS AND CULTURE. THE CSF HAD 183 MG/DL PROTEIN AND GLUCOSE <(><<)>10 MG/DL. ACHROMOBACTER XYLOSOXIDANS WAS AGAIN ISOLATED FROM THE CSF. CEFTAZIDIME 2720 MG (100 MG/KG) IV EVERY 8 HOURS AND GENTAMICIN 204 MG (7.5 MG/KG) IV EVERY 24 HOURS WERE EMPIRICALLY INITIATED DUE TO CONCERN FOR MEROPENEM RESISTANCE. GENTAMICIN WAS ADJUSTED TO 15 MG/KG IV EVERY 24 HOURS FOLLOWING THERAPEUTIC DRUG MONITORING IN AN EFFORT TO OPTIMIZE ACHIEVED PEAK CONCENTRATIONS. EXTRAPOLATED GENTAMICIN PEAK CONCENTRATION FOLLOWING A DOSE OF 10 MG/KG WAS 21 G/ML, WHICH WAS LIKELY SUBOPTIMAL DUE TO THE PREVIOUS GENTAMICIN MINIMUM INHIBITORY CONCENTRATION (MIC) OF 16 G/ML. UNFORTUNATELY AN MIC TAKING INTO ACCOUNT THE SYNERGY OF THE DUAL AGENTS WAS UNAVAILABLE, SO THE OPTIMAL PEAK CONCENTRATION FOR THE SYNERGISTIC GENTAMICIN REMAINED UNCLEAR. THE PATIENT¿S ESTIMATED VOLUME OF DISTRIBUTION BASED ON THIS PEAK WAS 0.5 L/KG. OVER THE FOLLOWING 5 DAYS, THE PATIENT SHOWED SIGNS OF CLINICAL IMPROVEMENT WITH NEGATIVE CSF CULTURES BUT WITHOUT RETURN TO BASELINE MENTATION. UPON DEMONSTRATION OF MEROPENEM SUSCEPTIBILITY, THERAPY WAS CHANGED TO MEROPENEM 1080 MG (40 MG/KG) IV EVERY 8 HOURS, INFUSED OVER 4 HOURS, AND GENTAMICIN WAS DISCONTINUED. CEFTAZIDIME WAS AVOIDED DUE TO RISK OF INFECTION WITH MULTIDRUG-RESISTANT ORGANISMS FOLLOWING ITS USE. GIVEN RECURRENCE DESPITE PREVIOUS THERAPY WITH MEROPENEM, SERUM MEROPENEM CONCENTRATIONS WERE EVALUATED TO ENSURE PHARMACACODYNAMIC TARGET ACHIEVEMENT. BLOOD SAMPLES WERE COLLECTED IN RED-TOP TUBES AND FROZEN FOR TRANSPORT TO (B)(6) LABORATORIES IN (B)(6). BLOOD SAMPLES WERE TO BE OBTAINED JUST PRIOR TO 10TH MEROPENEM DOSE, AT THE END OF THE 4-HOUR MEROPENEM INFUSION, 2 HOURS AFTER THE END OF THE INFUSION, AND 4 HOURS AFTER THE END OF THE INFUSION/JUST PRIOR TO THE 11TH DOSE. CEREBROSPINAL FLUID SAMPLE WAS TO BE IDEALLY OBTAINED AT END OF 4-HOUR MEROPENEM INFUSION, BUT NEUROSURGERY WORKFLOW NECESSITATED OBTAINING THE SAMPLE FROM THE EVD PRIOR TO ADMINISTRATION OF THE 10TH DOSE. BLOOD SAMPLES WERE OBTAINED AS PLANNED, BUT THE 11TH DOSE WAS ACCIDENTALLY INITIATED EARLY AND THE FINAL SAMPLE WAS REFLECTIVE OF MID-INFUSION RATHER THAN THE INTENDED TROUGH. CONCENTRATION DETERMINATION OCCURRED VIA QUANTITATIVE BIOASSAY IN ACCORDANCE WITH PREVIOUS REPORTS. SERUM CONCENTRATION RESULTS ARE AVAILABLE IN TABLE 3. USING STANDARD PHARMACOKINETIC CALCULATIONS TO MANIPULATE THE OBTAINED SERUM CONCENTRATIONS, THE PATIENT¿S VOLUME OF DISTRIBUTION WAS APPROXIMATELY 0.21 L/KG WHICH IS SIMILAR TO THE 0.3 TO 0.4 L/KG THAT HAS BEEN REPORTED PREVIOUSLY. THE PATIENT¿S ESTIMATED ELIMINATION CONSTANT (KE), CALCULATED FROM THE 2 VALUES COLLECTED AFTER CESSATION OF THE INFUSION, WAS 0.77 H-1 WHICH CORRELATES WITH AN ELIMINATION HALF-LIFE (T1/2) OF 54 MINUTES, WHICH IS CONSISTENT WITH WHAT IS REPORTED IN INDIVIDUALS >2 YEARS OF AGE. THE PATIENT¿S ESTIMATED MEROPENEM TROUGH CONCENTRATION WAS 2.5 G/ML, WHICH CORRELATES WITH A TROUGH CONCENTRATION IN THE CSF OF 0.05 TO 0.15 G/ML USING 2% TO 6% CSF¿BLOOD PENETRATION RATIO AS HAS BEEN REPORTED. THE MEROPENEM CONCENTRATION AT THE END OF THE INFUSION WAS 50 G/ML, INDICATING THAT THE CONCENTRATION THROUGHOUT THE 4-HOUR INFUSION MOST LIKELY REMAINED ABOVE THE MIC DURING THAT TIME. THE CORRELATING CSF MEROPENEM CONCENTRATION USING PREVIOUSLY REPORTED CSF PENETRATION RATIOS WOULD BE 1 TO 3 G/ML, WHICH IS CONSISTENT WITH THE REPORTED VALUE OF <(> <<)>5 G/ML. USING THE CALCULATED HALF-LIFE, THIS WOULD REPRESENT A MEROPENEM CONCENTRATION IN THE CSF THAT EXCEEDED THE MIC OF THE ORGANISM FOR 75% TO 95% OF THE DOSING INTERVAL, WHICH EXCEEDS THE 40% NEEDED FOR BACTERICIDAL ACTIVITY WITH CARBAPENEMS. IT WAS THEREFORE ASSUMED THAT PHARMACODYNAMICS TARGET ATTAINMENT FOR MEROPENEM WAS ACHIEVED. THE PATIENT CONTINUED TO IMPROVE CLINICALLY AND RETURNED TO BASELINE MENTAL STATUS BY DAY 10 OF MEROPENEM THERAPY. SIX WEEKS OF MEROPENEM WAS COMPLETED VIA PICC AT HOME WITH NO FURTHER RECURRENCES TO DATE.

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    434840 INFUSION PUMP PUMP, INFUSION, IMPLANTED, PROGRAMMABLE LKK MEDTRONIC NEUROMODULATION

    Patients

    Seq Age Sex Outcome Treatment
    1 00013 YR Hospitalization| R