PICU Bugs and Drugs: Rational Use of Antibiotics In The PICU

Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamatand my name is Rahul Damania and we come to you from Children's Healthcare of Atlanta Emory University School of Medicine. Today's episode is dedicated to the rational use of antibiotics in the PICUWe are delighted to be joined by two brilliant Pediatric clinical pharmacists Ms Whitney Moore and Ms. Stephanie Yasechko from Children's Healthcare of Atlanta.I will turn it over to Rahul to start with our patient case...CaseAn 8-year-old female (24 kg, 130 cm) with PMH significant for severe persistent asthma and history of multiple PICU admissions presents to the ED with swelling, redness and inability to bear weight in her (L) lower leg.Patient had just finished soccer practice the evening prior to her ED visit when she first noticed swelling and redness of her left lower leg. She also had a fever as well as some non-bloody, non-bilious emesis. Her past h/o is significant for poorly controlled asthma with multiple admissions to the PICU.Upon arrival to the ED, patient's BP was hypotensive, tachycardic, and tachypneic. She was given two 20 mL/kg NS boluses, and blood cultures were drawn in addition to a CBC, BMP, and UA.Labs were notable for an elevated white count, lactate, and serum Cr. Patient was given a dose of antibiotic, and transported to the PICU for further workup and management.Whitney and Stephanie welcome to PICU Doc on call.Thanks Rahul and Pradip for having us. Neither one of us have any financial disclosures or conflicts of interest.We want to divide today's discussion into 3 segments- antibiotic selection, transition into dosing and end with therapeutic monitoringWhitney, what are some of the factors to consider prior to choosing an antibiotic regimen in our patient case with a preliminary diagnosis of cellulitis of the left lower extremity with possible sepsis?Whitney: First and foremost you want to consider your host so really diving deep into the patient’s past medical history and secondly we should consider the likely pathogens that are causing the patient’s infection. In this case given the invasive nature of her infection and recent hospital admissions I would start Vancomycin and Cefepime. Once blood cultures results are back, we can then tailor or narrow her antibiotics based on susceptibilities.Stephanie what are some of the other factors to consider prior to starting antibiotics in this patient?Other things to consider include her multiple previous hospitalizations, significant exposure to broad-spectrum antibiotics, whether or not she is immunocompromised, the presence of chronic conditions like lung disease, ventilator/trach dependency, and if patient was a resident of a long term care facility. Additionally any history of organ or bone marrow transplant or malignancy with use of chemotherapy/radiation, and/or a history of growth of multiple drug resistant organisms.This is an important point - infectious disease is not just about the relevant pathogen or "bug" but it is also about understanding the host status!Stephanie -why vancomycin and cefepime in this case?In this patient the major pathogens to consider include: P. aeruginosa (give her multiple previous PICU admissions).Also she has extensive cellulitis which necessitates antibiotic coverage against Methicillin resistant staph aureus (MRSA) and Streptococcus pyogenes . So our options in this case include vancomycin for broad-spectrum gram positive coverage, and generally either piperacillin/tazobactam or cefepime for broad-spectrum gram negative and pseudomonal coverage.As you can see by patient’s Scr, it appears that she is presenting in AKI since we have no history of her having any type of renal impairment at baseline; therefore, to minimize additional AKI risk, cefepime would be our most appropriate choice for the time being. There is literature that shows us that the combination of vancomycin and piperacillin/tazobactam specifically has a much higher risk of AKI than other nephrotoxic combinations and should be avoided if possible.Whitney lets now transition from abx selection to dosing — how would you dose vancomycin and cefepime in our patient case?An appropriate dose of vancomycin to start out here would be 15 mg/kg, with a maximum of 1000 mg. However, instead of scheduling a defined frequency, pharmacy would recommend a x1 dose, and check a level in a couple of hours in patients who present with any type of unstable renal function. However, traditional vancomycin dosing in patients with normal renal function is either 20 mg/kg/dose IV every 8 hours or 15 mg/kg/dose IV every 6 hours with a max of 1000 mg/dose.Cefepime is traditionally dosed at 50 mg/kg/dose IV every 8 hours; however, since our patient has AKI, we should calculate her CrCl or estimated GFR to renally adjust the dose. As you all know there are a couple of equations we could use to calculate her clearance. But the modified Bedside Schwartz equation is the gold standard for pediatric patients. Once the GFR or CrCl is calculated we can then adjust the dose for her AKI.I think this is a great time to start to highlight the importance of collaboration between the intensivists, nursing & the pharmacy team. These children already are tenuous and as we treat with broad spectrum abx it is important to also consider the side effects such as nephrotoxicity of broad spectrum antibiotics.As we discussed specifics of dosing of Vanc and Cefepime, Stephanie, if we take a step back what are some of the other factors to consider prior to antibiotic dosing?In terms of selecting the most appropriate dose, we always want to consider factors like age, weight, renal/hepatic function, as well as the area in the body we wish to penetrate (CNS, bone, blood, etc.).Additionally, it is very important to identify whether or not the patient is currently receiving continuous renal replacement therapy(CRRT), plasma exchange, ECMO, or fluids and/or diuretics, because all of these can affect drugs quite significantly from a pharmacokinetic standpoint.Lexicomp (available either as a paper-back or online) is the gold standard for pediatric dosing. And of course your clinical pharmacist specialist is always available to help with dosing references, and can provide recommendations on how to most appropriately dose your specific patientWhitney how would you monitor the patient given evidence of AKI and the need for a nephrotoxic antibiotic such as vancomycin?Depending on the severity of the renal dysfunction, the vancomycin level can be checked anywhere from 8-24 hours post administrationA therapeutic steady-state drug concentration is generally reached after the administration of about 3-4 doses (or 4 to 5 half-lives). The therapeutic goal trough level is 10-15 mcg/mL for all infections, except for those harder to penetrate areas like the CNS or the heart. In these cases the target trough is higher at 15-20 mcg/mL.To summarize, those "hard to reach areas" such as the blood brain barrier or the heart — we should ensure a higher trough in order for us to reach therapeutic effect.Stephanie, what are important points regarding trough monitoring for vancomycin?Trough monitoring represents a therapeutic controversy within the pharmacy community, as recent vancomycin dosing guidelines have changed to now recommend area under the curve (AUC) guided monitoring as the most efficacious and safe way to monitor the drug given its narrow therapeutic range and increased nephrotoxic risk with trough monitoring.Here at our institution, we have not yet fully incorporated this new monitoring technique. We are reserving AUC monitoring for patients with MRSA bacteremia or unable to achieve therapeutic troughs with traditional dosing.This is a great practical example, as the bedside staff it is important to optimize communication as antibiotic troughs are time sensitive.Now that we have discussed vancomycin, Stephanie what about dosing and monitoring of cefepime in our patient?Cefepime, does not require therapeutic drug monitoring, so determination of an appropriate dose is dependent on CrCL, and it is important to recognize that continuous adjustments may need to be made as renal function improves or declines.Refer to Lexicomp for all renal dose adjustments. Rule of thumb, if CrCL > 50, a patient can be dosed normally. Anything less should be evaluated.Let's wrap up this section by summarizing some important dosing points for Vancomycin and Cefepime. Whitney, as your patient improves how would you approach de-escalation of abx?There are two important points I want you to remember when dosing vancomycin and cefepime. First, is knowing the maximum dose of each medication. Cefepime we max the dose at 2000 mg per dose, and our initial starting dose maximum for vancomycin is 1000 mg, as mentioned. We can go up to 1250 but only after we have drawn levels and need to. But knowing the maximum dose is an important point to consider when dosing a large patient because you don’t want to exceed an adult dose. The second important point I want you to remember is calculating the patient’s clearance and adjusting the dose and/or...