Protocol for Submission of the partial fulfillment of the Master Degree in Pharmaceutical Sciences (Clinical Pharmacy)

Title: Clinical Outcomes of Prolonged versus Intermittent Infusion of Antibiotics in Critically ill Pediatric Patients with Sepsis at
Assiut University Children's Hospital

 Rationale:
1. An empiric antibiotic protocol in the pediatric intensive care unit incorporating risk stratification for
healthcare associated infections resulted in increased appropriateness of empiric antibiotics and in
decreased time to appropriate antibiotics in critically ill children with infection.
2. From a pediatric care perspective, it is critical to optimize the dosing of the currently available
antibacterial agents based on drug-specific pharmacokinetic and pharmacodynamic parameters, thus
increasing the probability that positive patient outcomes are maximized while minimizing the selective
pressure for emergence of antibiotic resistance.

 Pediatric Intensive Care Unit Empiric Antibiotic Pathway including risk factors for infection to place
patients at high or low risk Antibiotics
 Use High Risk Antibiotics If Patient with any of the following Risk Factor for Resistant Organisms:
1. Central line, Prior hospitalization, Immunocompromised Patients,
2. Chronic medical condition (COPD, Asthma, DM, CHF, CKD, CP, Chronic hepatitis, Epilepsy, Sickle cell
anemia and other hemoglobin disorders) ,
3. Autoimmune diseases (Ulcerative colitis, Lupus erythematosus, Crohn's disease),
4. Immunosuppressive medications (Corticosteroid drugs > 2 weeks, Methotrexate, Cyclophosphamide,
Rituximab, Azathioprine, Cyclosporine, Infliximab)
5. Patient already on broad spectrum antibiotics (Any regimen including ceftriaxone, cefotaxime,
cefepime, piperacillin-tazobactam, ciprofloxacin, or aztreonam alone or in combination with
vancomycin or clindamycin( :
 High Risk Antibiotics: Administer antibiotics in the order listed
1. Cycled aminoglycoside (Gentamicin, tobramycin, and amikacin)
2. Cycled anti-Pseudomonal β-lactam (Cefepime, Piperacillin-tazobactam, and Carbapenem)
3. Vancomycin
4. Other agents as clinically indicated: See Below
5. Consider additional antimicrobials with the following clinical scenarios
a) Antifungal prophylaxis: Fluconazole 12 mg/kg on day 1, followed by 6 mg/kg/ day (Typically
recommended for High-risk ICU patients)
b) Candidiasis Disseminated, acute (including catheter Fungemia infection): See 2018 Nelson’s Pediatric
Antimicrobial Therapy Page 150, 151
c) Toxic shock syndrome (toxin-producing strains of S aureus [including MRSA] or group A
streptococcus):
 Clindamycin 30–40 mg/kg/day div q8h, Clindamycin added for the initial 48–72 h of therapy to
decrease toxin production.
 IVIG may provide additional benefit by binding circulating toxin
d) Patient with Suspected CNS source and Intra-abdominal Source: Add metronidazole for anaerobic
coverage only with cefepime
e) For suspect Mycoplasma/atypical pneumonia agents, particularly in school-aged children:
Azithromycin or Clarithromycin, or Doxycycline
f) Suspicion of Influenza A and B: Oseltamivir
g) Herpes simplex virus: Acyclovir

Protocol Submitted by Clinical Pharmacist Rania Saad Mahmoud Ali

Supervisors: Prof. Dr. Mohamed Mahmoud Mohamed Abd El Latif, Prof. Dr. Maher Mokhtar Ahmed, Dr. Sahar Badr Hassan
1

PICU Empiric Antimicrobial Protocol for Patients with Severe Sepsis/Septic Shock Approved By: Prof. Dr. Azza Ahmed El-Tayeb
 Protocol for Submission of the partial fulfillment of the Master Degree in Pharmaceutical Sciences (Clinical Pharmacy)
Title: Clinical Outcomes of Prolonged versus Intermittent Infusion of Antibiotics in Critically ill Pediatric Patients with Sepsis at
Assiut University Children's Hospital

 Adjuvant Therapies
A. Stress Dose Hydrocortisone:
 Indications: If the patient remains hypotensive despite adequate fluid resuscitation and titration of
one vasoactive infusion, consider stress-dose hydrocortisone for Critical Illness-Related Corticosteroid
Insufficiency. If possible, send a random blood cortisol level prior to starting hydrocortisone.
 Dosing Hydrocortisone
1. BSA: 100 mg/m2 load, then 100 mg/m2/day divided q 4 hours IV
2. mg/kg: 2 mg/kg IV load (max 100 mg), then 2 mg/kg/day divided q 4 hours IV
 Discontinuing Hydrocortisone
1. Cortisol ≥ 18 microgram/dL (if level drawn before hydrocortisone given)
2. Wean or discontinue hydrocortisone when vasopressors no longer required
B. Diuresis
 Evaluate % fluid overload (FO) daily:
1. % FO=(Current weight-Admission weight)/Admission weight x 100
2. Consider a trial of fluid restriction using a TFL prior to diuresis, while still maximizing nutrition.
3. Hemodynamically stable patients with > 10-15% fluid overload, consider diuretic use: Furosemide
4. When appropriate fluid therapy is administered, the body weight should decrease by 0.5-1.0% daily,
and the serum sodium concentration should remain steady.
5. A more rapid weight loss and increasing serum sodium indicate inadequate fluid replacement.
6. An absence of weight loss with decreasing serum sodium suggests excess free-water replacement.

Protocol Submitted by Clinical Pharmacist Rania Saad Mahmoud Ali

Supervisors: Prof. Dr. Mohamed Mahmoud Mohamed Abd El Latif, Prof. Dr. Maher Mokhtar Ahmed, Dr. Sahar Badr Hassan
2

PICU Empiric Antimicrobial Protocol for Patients with Severe Sepsis/Septic Shock Approved By: Prof. Dr. Azza Ahmed El-Tayeb
 Protocol for Submission of the partial fulfillment of the Master Degree in Pharmaceutical Sciences (Clinical Pharmacy)
Title: Clinical Outcomes of Prolonged versus Intermittent Infusion of Antibiotics in Critically ill Pediatric Patients with Sepsis at
Assiut University Children's Hospital

 Recommended Laboratory Studies

 Frequency Comment
BLOOD
1. Blood Culture  Obtain prior to antibiotics when possible, but do
not delay antibiotic administration
2. CBC, differential
3. An arterial-blood gas (ABG)
4. Lactate
5. Hepatic function
6. Kidney function
7. Electrolytes (esp. ionized Ca)
8. PT/INR/PTT
9. C-reactive protein (CRP) Q 72 hr
10. Cortisol Random  Send if risk of adrenal insufficiency
1. Catecholamine resistant shock
2. Congenital adrenal hyperplasia
3. Prolonged steroid treatment (> 2 weeks)
URINE
1. Urinalysis
2. Urine Culture  Catheterized
1. Short-term collect specimen by aseptically aspirating
from port of urinary catheter
2. Long-term: first change urinary catheter then collect
specimen by aseptically aspirating port of urinary
catheter
3. Caution: straight cath for urine collection may result
in iatrogenic UTI
CSF Profile, Gram Stain, Culture As clinically indicated
Respiratory Gram Stain, Culture
1. Sputum, Endotracheal or Tracheal  Ensure specimen comprises sputum (not saliva /
Aspirates, Nasopharygeal Aspirates / food); samples of saliva only will not be processed
Secretions
2. Bronchial alveolar lavage (BAL) and mini-  Obtained by bronchosopy or with use of a special
BAL catheter (mini-BAL); requires prompt transport to
the laboratory for processing; not acceptable for
anaerobic cultures; fluid should be concentrated for
optimal yield for stains and cultures.
Stool Culture, Routine  In general do not process for bacterial pathogens if
patient develops symptoms more than 3 days after
admission; consider C. difficile for hospitalized
patients with diarrhea
 Formed stools in general should not be submitted

Protocol Submitted by Clinical Pharmacist Rania Saad Mahmoud Ali

Supervisors: Prof. Dr. Mohamed Mahmoud Mohamed Abd El Latif, Prof. Dr. Maher Mokhtar Ahmed, Dr. Sahar Badr Hassan
3

PICU Empiric Antimicrobial Protocol for Patients with Severe Sepsis/Septic Shock Approved By: Prof. Dr. Azza Ahmed El-Tayeb
 Protocol for Submission of the partial fulfillment of the Master Degree in Pharmaceutical Sciences (Clinical Pharmacy)
Title: Clinical Outcomes of Prolonged versus Intermittent Infusion of Antibiotics in Critically ill Pediatric Patients with Sepsis at
Assiut University Children's Hospital

 Antimicrobial Dosing in Critically Ill-Patients

 Cefepime Hydrochloride: Fourth Generation Cephalosporin
1. General dosing, susceptible infection: Infants, Children, and Adolescents: IM, IV:
a. Mild to moderate infection: 100 mg/kg/day, max 4 g/day q12h
b. Severe infection and Bacterial meningitis: 150 mg/kg/day, max 6 g/day q8h
2. Renal Impairment Dosing: Based on doses of 50 mg/kg/dose q 8 to 12 hrs.
a. GFR >50 mL/minute/1.73 m2: No adjustment needed
b. GFR 10 to 50 mL/minute/1.73 m2: 50 mg/kg/dose every 24 hours
c. GFR <10 mL/minute/1.73 m2: 50 mg/kg/dose every 48 hours
d. Intermittent hemodialysis: 50 mg/kg/dose every 24 hours
e. Peritoneal dialysis (PD): 50 mg/kg/dose every 24 hours
f. Continuous renal replacement therapy (CRRT): 50 mg/kg/dose every 12 hours
3. Hepatic Impairment Dosing: No dosage adjustments necessary
 Preparation for Parenteral Administration
a. IV: Reconstitute 500 mg vial with 5 mL and 1 or 2 g vial with 10 mL of a compatible diluent (resulting
concentration of 100 mg/mL for 500 mg and 1 g vial and 160 mg/mL for 2 g vial); further dilute in D5W,
NS, D10W, D5NS, or D5LR; final concentration should not exceed 40 mg/mL.
b. IM: Reconstitute 500 mg or 1 g vial with 1.3 mL or 2.4 mL, respectively, of SWFI, NS, D5W, lidocaine
0.5% or 1%, or bacteriostatic water for injection to a final concentration of 280 mg/mL
 Parenteral Administration
a. IV: Administer as an intermittent IV infusion over 30 minutes.
b. IM: Administer by deep IM injection into large muscle mass
1. Storage/Stability: Vials: Store intact vials at 20°C to 25°C. Protect from light. After reconstitution,
stable in NS and D5W for 24 hours at 20°C to 25°C and 7 days at 2°C to 8°C (36°F to 46°F).

 Piperacillin and Tazobactam: Beta-lactam and Beta-lactamase Inhibitor Combination
 Note: Dosage recommendations are based on the piperacillin component.
1. General dosing, susceptible infection: Severe infection:
a. Infants <2 months: IV: 80 mg piperacillin/kg/dose every 6 hours
b. Infants 2 to 9 months: IV: 80 mg piperacillin/kg/dose every 8 hours
c. Infants >9 months, Children, and Adolescents: IV: 100 mg piperacillin/kg/dose every 8 hours; maximum
daily dose: 16 g piperacillin/day
2. Renal Impairment Dosing based on a usual dose of 200 to 300 mg piperacillin kg/day q 6 hours.
a. GFR >50 mL/minute/1.73 m2: No adjustment required
b. GFR 30 to 50 mL/minute/1.73 m2: 35 to 50 mg piperacillin/kg/dose every 6 hours
c. GFR <30 mL/minute/1.73 m2: 35 to 50 mg piperacillin/kg/dose every 8 hours
d. Intermittent hemodialysis (IHD): Hemodialysis removes 30% to 40% of a piperacillin/tazobactam dose:
50 to 75 mg piperacillin/kg/dose every 12 hours
e. Peritoneal dialysis (PD): Peritoneal dialysis removes 21% of tazobactam and 6% of piperacillin: 50 to 75
mg piperacillin/kg/dose every 12 hours
f. Continuous renal replacement therapy (CRRT): 35 to 50 mg piperacillin/kg/dose every 8 hours
3. Dosing Hepatic Impairment: No dosing adjustment required

Protocol Submitted by Clinical Pharmacist Rania Saad Mahmoud Ali

Supervisors: Prof. Dr. Mohamed Mahmoud Mohamed Abd El Latif, Prof. Dr. Maher Mokhtar Ahmed, Dr. Sahar Badr Hassan
4

PICU Empiric Antimicrobial Protocol for Patients with Severe Sepsis/Septic Shock Approved By: Prof. Dr. Azza Ahmed El-Tayeb
 Protocol for Submission of the partial fulfillment of the Master Degree in Pharmaceutical Sciences (Clinical Pharmacy)
Title: Clinical Outcomes of Prolonged versus Intermittent Infusion of Antibiotics in Critically ill Pediatric Patients with Sepsis at
Assiut University Children's Hospital

 Preparation for Administration: Parenteral:

a. Reconstitution: Single-dose vials: Reconstitute with 20 mL of diluent (NS, D5W, or SWFI) per 4,000 mg
of piperacillin to yield a concentration of piperacillin 200 mg/mL and tazobactam 25 mg/mL
b. Intermittent IV infusion: Further dilute dose in D5W or NS to a usual final concentration of piperacillin
20 to 80 mg/mL
 Administration: Parenteral:
a. Intermittent IV infusion: Administer over 30 minutes
b. Extended IV infusion: Administration over 3 to 4 hours has been reported in pediatric and adult
patients.
 Storage/Stability: Vials: Store intact vials at 20°C to 25°C. Discard any unused portion after 24 hours if
stored at 20°C to 25°C or after 48 hours if stored at 2°C to 8°C. Stability in an ambulatory IV infusion
pump has been demonstrated for a period of 12 hours at room temperature.

 Meropenem: Carbapenem
1. General dosing, susceptible infection (non-CNS): IV: 20 mg/kg/dose q8h; maximum: 1,000 mg/dose
2. Acute sepsis: 75 mg/kg/day div q8h
3. Cystic fibrosis, pulmonary exacerbation: IV: 40 mg/kg/dose q8h; maximum dose: 2,000 mg/dose
4. Meningitis: IV: 40 mg/kg/dose q8h; maximum dose: 2,000 mg/ dose
5. Renal Impairment Dosing Based on doses of 20 to 40 mg/kg/dose every 8 hours:
a. GFR >50 mL/minute/1.73 m2: No adjustment required.
b. GFR 30 to 50 mL/minute/1.73 m2: Administer 20 to 40 mg/kg/dose every 12 hours
c. GFR 10 to 29 mL/minute/1.73 m2: Administer 10 to 20 mg/kg/dose every 12 hours
d. GFR <10 mL/minute/1.73 m2: Administer 10 to 20 mg/kg/dose every 24 hours
e. Intermittent hemodialysis (IHD): Meropenem and metabolite are readily dialyzable: 10 to 20
mg/kg/dose every 24 hours; on dialysis days give dose after hemodialysis
f. Peritoneal dialysis (PD): 10 to 20 mg/kg/dose every 24 hours
g. Continuous renal replacement therapy (CRRT): 20 to 40 mg/kg/dose every 12 hours
6. Hepatic Impairment Dosing: No dosage adjustment necessary.
 Preparation for Administration
a. Reconstitute 500 mg and 1 g vials with 10 mL and 20 mL SWFI respectively to yield a concentration of
50 mg/mL. For IV infusion may further dilute with D5W or NS to a final concentration ranging from 1 to
20 mg/mL.
 Parenteral Administration:
a. Infants <3 months: Administer as an IV infusion over 30 minutes
b. Infants ≥3 months, Children, Adolescents, and Adults: Administer IV infusion over 15 to 30 minutes
c. Some studies have demonstrated enhanced pharmacodynamic effects when extending intermittent
infusions 3 to 4 hours
 Storage/Stability: Dry powder should be stored at controlled room temperature 20°C to 25°C, Stability
in vial when constituted (up to 50 mg/mL) with:
a. SWFI: Stable for up to 3 hours at up to 25°C (77°F) or for up to 13 hours at up to 5°C
b. Infusion admixture: Data exist supporting stability (admixed with NS at a concentration of 20 mg/mL)
at room temperature for ≤ 4 hours and under refrigeration ≤24 hours
Protocol Submitted by Clinical Pharmacist Rania Saad Mahmoud Ali
Supervisors: Prof. Dr. Mohamed Mahmoud Mohamed Abd El Latif, Prof. Dr. Maher Mokhtar Ahmed, Dr. Sahar Badr Hassan
5

PICU Empiric Antimicrobial Protocol for Patients with Severe Sepsis/Septic Shock Approved By: Prof. Dr. Azza Ahmed El-Tayeb
 Protocol for Submission of the partial fulfillment of the Master Degree in Pharmaceutical Sciences (Clinical Pharmacy)
Title: Clinical Outcomes of Prolonged versus Intermittent Infusion of Antibiotics in Critically ill Pediatric Patients with Sepsis at
Assiut University Children's Hospital

 Ertapenem: Carbapenem
1. General dosing, susceptible infection: Note: IV therapy may be administered for up to 14 days; IM for
up to 7 days; refer to disease-state specific durations.
a. Infants and Children: Severe infections: IM, IV: 15 mg/kg/dose twice daily; maximum single dose: 500
mg/dose
b. Adolescents: IM, IV: 1,000 mg once daily
2. Renal Impairment Dosing:
a. CrCl >30 mL/minute/1.73 m2: No dosage adjustment necessary.
b. CrCl ≤30 mL/minute/1.73 m2 and ESRD: Once Daily
c. Hemodialysis: When the daily dose is given within 6 hours prior to hemodialysis, a supplementary dose
of 150 mg is required following hemodialysis. If Ertapenem is given at least 6 hours prior to
hemodialysis, no supplementary dose is needed.
3. Hepatic Impairment Dosing: Adjustments cannot be recommended
 Preparation for Parenteral Administration
a. IM: Reconstitute 1,000 mg vial with 3.2 mL of 1% lidocaine HCl injection (without epinephrine);
resultant concentration: 280 mg/mL. Shake well.
b. Intermittent IV infusion: Reconstitute 1,000 mg vial with 10 mL of SWFI, NS, or bacteriostatic water for
injection using a syringe with a 21-gauge or smaller diameter needle (needleless IV system is not
recommended); shake well; resultant concentration: 100 mg/mL. Further dilute dose with NS; for
adolescents and adults, transfer dose to 50 mL NS; for children, dilute dose to a final concentration ≤20
mg/mL.
 Parenteral Administration
a. IM: Administer deep into a large muscle mass such as the gluteus maximus or lateral part of the thigh.
Avoid injection into a blood vessel.
b. Intermittent IV infusion: Infuse over 30 minutes. Do not coinfuse with other medications. Do not
infuse with dextrose-containing solutions.
 Storage/Stability
a. Prior to reconstitution, store vials at ≤25°C. The reconstituted IM solution should be used within 1 hour
after preparation. The reconstituted IV solution may be stored at room temperature (25°C) and used
within 6 hours, or stored for 24 hours under refrigeration (5°C) and used within 4 hours after removal
from refrigeration. Do not freeze.

Protocol Submitted by Clinical Pharmacist Rania Saad Mahmoud Ali

Supervisors: Prof. Dr. Mohamed Mahmoud Mohamed Abd El Latif, Prof. Dr. Maher Mokhtar Ahmed, Dr. Sahar Badr Hassan
6

PICU Empiric Antimicrobial Protocol for Patients with Severe Sepsis/Septic Shock Approved By: Prof. Dr. Azza Ahmed El-Tayeb
 Protocol for Submission of the partial fulfillment of the Master Degree in Pharmaceutical Sciences (Clinical Pharmacy)
Title: Clinical Outcomes of Prolonged versus Intermittent Infusion of Antibiotics in Critically ill Pediatric Patients with Sepsis at
Assiut University Children's Hospital

 Vancomycin
 Dosing: Doses require adjustment in renal impairment. Consider single-dose administration with serum
concentration monitoring rather than scheduled dosing in patients with urine output <1 mL/kg/hour or
if serum creatinine significantly increases from baseline (eg, doubles).
1. General dosing, susceptible infection: IV: 45 to 60 mg/kg/day divided every 6 to 8 hours.
2. C. difficile infection: Oral: 40 mg/kg/day divided every 6 to 8 hours for 7 to 10 days; maximum daily
dose: 2,000 mg/day
3. Acute exacerbation: May require vancomycin 60–80 mg/kg/day IV div q8h
4. Renal Impairment Dosing:
 Oral: There are no dosage adjustments.
 IV: Based on doses of 10 mg/kg/dose every 6 hours or 15 mg/kg/dose every 8 hours:
a. GFR 30 to 50 mL/minute/1.73 m2: 10 mg/kg/dose every 12 hours
b. GFR 10 to 29 mL/minute/1.73 m2: 10 mg/kg/dose every 18 to 24 hours
c. GFR <10 mL/minute/1.73 m2: 10 mg/kg/dose; redose based on serum concentrations
d. Intermittent hemodialysis: 10 mg/kg/dose; redose based on serum concentrations
e. Peritoneal dialysis (PD): 10 mg/kg/dose; redose based on serum concentrations
f. Continuous renal replacement therapy (CRRT): 10 mg/kg/dose every 12 to 24 hours; monitor serum
concentrations
5. Hepatic Impairment Dosing: Oral, IV: There are no dosage adjustments
 Preparation for Administration
a. Oral: Powder for injection: See below Extemporaneous Preparations section for details.
b. Parenteral: Reconstitute vials with SWFI to a final concentration of 50 mg/mL. Further dilute the
reconstituted solution in a compatible diluent (eg, D5W, NS) to a final concentration ≤5 mg/mL. In fluid
restricted patients, a concentration of 10 mg/mL may be used, but the risk of infusion reactions
increases.
 Administration
a. Oral: Powder for injection: Reconstituted powder for injection (not premixed solution) may be diluted
and used for oral administration; common flavoring syrups may be added to improve taste. The
unflavored, diluted solution may also be administered via nasogastric tube.
b. Parenteral: Administer intermittent IV infusion over 60 minutes.
 Storage/Stability:
a. Vials: Store at 20°C to 25°C. After initial reconstitution with SWFI, solutions are stable for 96 hours if
refrigerated. After further dilution with D5W or NS to a concentration of 5 mg/mL, the solution may be
stored in a refrigerator for 63 days without significant loss of potency.
 Extemporaneous Preparations
a. Oral Solution: Using a vial of vancomycin powder for injection (reconstituted to 50 mg/mL), add the
appropriate volume for the dose to 30 mL of water and administer orally or via NG tube. For oral
administration, common flavoring syrups may be added to improve taste.

Protocol Submitted by Clinical Pharmacist Rania Saad Mahmoud Ali

Supervisors: Prof. Dr. Mohamed Mahmoud Mohamed Abd El Latif, Prof. Dr. Maher Mokhtar Ahmed, Dr. Sahar Badr Hassan
7

PICU Empiric Antimicrobial Protocol for Patients with Severe Sepsis/Septic Shock Approved By: Prof. Dr. Azza Ahmed El-Tayeb
 Protocol for Submission of the partial fulfillment of the Master Degree in Pharmaceutical Sciences (Clinical Pharmacy)
Title: Clinical Outcomes of Prolonged versus Intermittent Infusion of Antibiotics in Critically ill Pediatric Patients with Sepsis at
Assiut University Children's Hospital

 Linezolid
1. General dosing, susceptible infection (mild, moderate, or severe): Oral, IV:
a. Infants and Children <12 years: 10 mg/kg/dose every 8 hours, maximum dose: 600 mg
b. Children ≥12 years and Adolescents: 600 mg every 12 hours
2. Renal Impairment Dosing: Based on doses of 10 mg/kg/dose every 8 hours (for ages <5 years) or
every 12 hours (for ages 5 to 11 years(
a. Intermittent hemodialysis: 10 mg/kg/dose every 12 hours
b. Peritoneal dialysis (PD): 10 mg/kg/dose every 12 hours
c. Continuous renal replacement therapy (CRRT): No adjustment necessary
3. Hepatic Impairment Dosing
a. Mild to moderate impairment (Child Pugh class A or B): No adjustment is recommended.
b. Severe hepatic impairment (Child Pugh Class C): Use has not been adequately evaluated.
 Preparation for Administration
a. Oral suspension: Reconstitute with 123 mL of distilled water (in 2 portions); shake vigorously.
Concentration is 100 mg/5 mL. Prior to administration mix gently by inverting bottle; do not shake.
 Administration
a. Oral: Administer with or without food. With reconstituted suspension, gently invert bottle 3-5 times
before use. Do not shake.
b. Parenteral: IV: Check infusion bag for minute leaks and solution for particulate matter prior to
administration. Administer without further dilution over 30 to 120 minutes. When the same
intravenous line is used for sequential infusion of other medications, flush line with D5W, NS, or LR
before and after infusing linezolid. The yellow color of the injection may intensify over time without
affecting potency.
 Storage/Stability
a. Infusion: Store at 25°C. Protect from light and freezing. Keep infusion bags in overwrap until ready for
use.
b. Oral suspension: Store at 25°C; following reconstitution store at room temperature and use suspension
within 21 days. Protect from light.

 Metronidazole (Systemic)
 Using adjusted body weight in obese children. Dosing weight = IBW + 0.45 (TBW-IBW(
1. General dosing, susceptible infection: Infants, Children, and Adolescents:
a. Oral: 15 to 50 mg/kg/day in divided doses 3 times daily; maximum daily dose: 2,250 mg/day
b. IV: 22.5 to 40 mg/kg/day in divided doses 3 or 4 times daily; maximum daily dose: 4,000 mg/day
2. Renally adjusted dose are based on doses of 15 to 30 mg/kg/day divided every 6 to 8 hours.
a. GFR ≥10 mL/minute/1.73 m2: No adjustment required
b. GFR <10 mL/minute/1.73 m2: 4 mg/kg/dose every 6 hours
c. Intermittent hemodialysis (IHD): Extensively removed by hemodialysis: 4 mg/kg/dose every 6 hours
d. Peritoneal dialysis (PD): Extensively removed by peritoneal dialysis: 4 mg/kg/dose every 6 hours
e. Continuous renal replacement therapy (CRRT): No adjustment required

Protocol Submitted by Clinical Pharmacist Rania Saad Mahmoud Ali

Supervisors: Prof. Dr. Mohamed Mahmoud Mohamed Abd El Latif, Prof. Dr. Maher Mokhtar Ahmed, Dr. Sahar Badr Hassan
8

PICU Empiric Antimicrobial Protocol for Patients with Severe Sepsis/Septic Shock Approved By: Prof. Dr. Azza Ahmed El-Tayeb
 Protocol for Submission of the partial fulfillment of the Master Degree in Pharmaceutical Sciences (Clinical Pharmacy)
Title: Clinical Outcomes of Prolonged versus Intermittent Infusion of Antibiotics in Critically ill Pediatric Patients with Sepsis at
Assiut University Children's Hospital

3. Dosing: Hepatic Impairment: Infants, Children, and Adolescents:

a. Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary; use with
caution and monitor for adverse events
b. Severe impairment (Child-Pugh class C):
 Immediate release tablets, injection: Reduce dose by 50%
 Extended release tablets: Use is not recommended.
 Alternate dosing: The authors recommended the dose be reduced accordingly (clearance was
reduced by ~62%) and the frequency may be prolonged (eg, every 12 hours instead of every 6
hours). In another single IV dose study using metronidazole metabolism to predict hepatic function,
patients classified as Child-Pugh class C demonstrated a half-life of ~21.5 hours.
 Administration
a. Oral: Immediate release tablets and capsules: May administer with food to minimize GI upset,
Extended release: Should be taken on an empty stomach (1 hour before or 2 hours after meals); do not
split, chew, or crush.
b. Parenteral: Administer undiluted (5 mg/mL) by slow intermittent infusion over 30 to 60 minutes. Avoid
contact of drug solution with equipment containing aluminum.
 Storage/Stability:
a. Oral: Store at 15°C to 25°C. Protect the tablets from light.
b. Injection: Store at 20°C to 25°C. Protect from light. Avoid excessive heat. Do not refrigerate. Do not
remove unit from overwrap until ready for use. Discard unused solution.

 Acyclovir (Systemic): Antiviral Agent, Parenteral
 Note: Obese patients should be dosed using ideal body weight. Parenteral IV doses >15 mg/kg/dose or
500 mg/m2 may be associated with an increased risk of nephrotoxicity; close monitoring of renal
function is recommended.
1. Herpes simplex infection
a. 60 mg/kg/day IV as 1–2 h infusion div q8h for 21 days for infants ≤ 4 mo; for older infants and children,
30–45 mg/kg/day IV for 21 days
2. Renal Impairment: Infants, Children and Adolescents: IV:
a. CrCl >50 mL/minute/1.73 m2: No dosage adjustment necessary
b. CrCl 25 to 50 mL/minute/1.73 m2: Administer the usual recommended dose q 12 hours
c. CrCl 10 to <25 mL/minute/1.73 m2: Administer the usual recommended dose q 24 hours
d. CrCl <10 mL/minute/1.73 m2: Administer 50% of the usual recommended dose q 24 hours (eg, if the
usual recommended dose is 10 mg/kg/dose every 8 hours, then administer 5 mg/kg/dose every 24
hours)
e. Intermittent hemodialysis (IHD): Dialyzable (60% reduction following a 6-hour session): 5 mg/kg/dose
every 24 hours; administer after hemodialysis on dialysis days
f. Peritoneal dialysis (PD): 5 mg/kg/dose every 24 hours; no supplemental dose needed
g. Continuous renal replacement therapy (CRRT): 10 mg/kg/dose every 12 hours
3. Hepatic Impairment: There is no dosage adjustments provided in the manufacturer's labeling.

Protocol Submitted by Clinical Pharmacist Rania Saad Mahmoud Ali

Supervisors: Prof. Dr. Mohamed Mahmoud Mohamed Abd El Latif, Prof. Dr. Maher Mokhtar Ahmed, Dr. Sahar Badr Hassan
9

PICU Empiric Antimicrobial Protocol for Patients with Severe Sepsis/Septic Shock Approved By: Prof. Dr. Azza Ahmed El-Tayeb
 Protocol for Submission of the partial fulfillment of the Master Degree in Pharmaceutical Sciences (Clinical Pharmacy)
Title: Clinical Outcomes of Prolonged versus Intermittent Infusion of Antibiotics in Critically ill Pediatric Patients with Sepsis at
Assiut University Children's Hospital

 Preparation for Administration

a. Parenteral: Reconstitute vial for injection to 50 mg/mL with SWFI; do not use bacteriostatic water
containing benzyl alcohol or parabens. For intravenous infusion, dilute in D5W, D5NS, D51/4NS, D51/2NS,
LR, or NS to a final concentration ≤ 7 mg/mL. In fluid restricted patients, concentrations up to 10
mg/mL have been infused; concentrations >10 mg/mL increase the risk of phlebitis.
 Administration
a. Parenteral: Administer by slow IV infusion over at least 1 hour; rapid infusion is associated with
nephrotoxicity due to crystalluria and renal tubular damage and should be avoided. Maintain adequate
hydration during therapy. Avoid IV push, IM, or SubQ administration.
b. Acyclovir IV is an irritant (depending on concentration); avoid extravasation. If extravasation occurs,
stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated
solution (do NOT flush the line); remove needle/cannula; elevate extremity. Apply dry warm
compresses. Intradermal hyaluronidase may be considered for refractory cases (Reynolds 2014).
c. Vesicant/Extravasation Risk: Irritant at concentrations >7 mg/mL
 Storage/Stability
a. Powder for injection: Store undiluted vials at 15°C to 25°C (59°F to 77°F). Following reconstitution (final
concentration 50 mg/mL), solution is stable for 12 hours at room temperature.
b. Solution for injection: Store solution at 20°C to 25°C (68°F to 77°F).
c. Do not refrigerate reconstituted solutions or solutions diluted for infusion as they may precipitate.
Once diluted for infusion with NS or D5W, use within 24 hours.

 Gentamicin (Systemic): Aminoglycoside
 General dosing, susceptible infection:
1. Bacterial meningitis, Bacterial sepsis, Infection of skin AND/OR subcutaneous tissue, Respiratory
tract infection (Severe), Intra-abdominal infection, complicated, Urinary tract infectious disease
(Severe) and (Infective endocarditis FDA dosage)
a. (Children, 1 year or older): 6 to 7.5 mg/kg/day IV for 7 to 10 days. Difficult or complicated infections
may require a longer duration of treatment and the dosage should be reduced when clinically
indicated.
b. (Infants and neonates, 1 year or younger): 7.5 mg/kg/day IV for 7 to 10 days
2. Cystic fibrosis: IV: 10 to 12 mg/kg/dose every 24 hours
3. Renal Impairment: Renally adjusted dose recommendations are based on doses of 7.5 mg/kg/day:
a. GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary
b. GFR 30 to 50 mL/minute/1.73 m2: Administer 5 mg/kg/day
c. GFR 10 to 29 mL/minute/1.73 m2: Administer 2.5 mg/kg/day
d. GFR <10 mL/minute/1.73 m2: Administer every 2.5 mg/kg/day 48 to 72 hours
e. Intermittent hemodialysis: 2 mg/kg/dose; redose as indicated by serum concentration
f. Peritoneal dialysis (PD): 2 mg/kg/dose; redose as indicated by serum concentration
g. Continuous renal replacement therapy (CRRT): 5 mg/kg/dose every 24 hours, monitor serum
concentrations
4. Hepatic Impairment:
a. There are no dosage adjustments

Protocol Submitted by Clinical Pharmacist Rania Saad Mahmoud Ali

Supervisors: Prof. Dr. Mohamed Mahmoud Mohamed Abd El Latif, Prof. Dr. Maher Mokhtar Ahmed, Dr. Sahar Badr Hassan
10

PICU Empiric Antimicrobial Protocol for Patients with Severe Sepsis/Septic Shock Approved By: Prof. Dr. Azza Ahmed El-Tayeb
 Protocol for Submission of the partial fulfillment of the Master Degree in Pharmaceutical Sciences (Clinical Pharmacy)
Title: Clinical Outcomes of Prolonged versus Intermittent Infusion of Antibiotics in Critically ill Pediatric Patients with Sepsis at
Assiut University Children's Hospital

 Preparation for Administration

a. IV: May dilute in NS or D5W, The concentration of the pediatric-specific product is 10 mg/mL.
 Administration
a. IM: Administer undiluted by deep IM route. Slower absorption and lower peak concentrations,
probably due to poor circulation in the atrophic muscle, may occur following IM injection; in paralyzed
patients, suggest IV route.
b. (IV bolus dosing): Administer IV bolus over 3 to 5 minutes
c. Intermittent IV: Administer as diluted solution by slow intermittent infusion over 30 to 120 minutes;
usual infusion time is 30 to 60 minutes; consider longer infusion time (60 to 120 minutes) with high
doses. Avoid formulations with preservatives in neonates and infants.
 Storage/Stability
a. Evidence to date suggests that repackaging of gentamicin in plastic syringes results in significant loss of
potency as compared to glass, disposable syringes. Glass syringes should be used for long-term storage
of gentamicin. This storage should not exceed 30 days
b. Store premixed bags at 20°C to 25°C. Protect from freezing. IV infusion solutions mixed in NS or D5W
are stable for 48 hours at room temperature and refrigeration.

 Amikacin (Systemic): Aminoglycoside
 Note: Individualization is critical because of the low therapeutic index. Dosage should be based on an
estimate of ideal body weight. In morbidly obese children and adolescents, dosage requirement may
best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW). Initial dosing recommendation
presented; dosage should be individualized based upon serum concentration monitoring. Initial and
periodic plasma drug concentrations (eg, peak and trough with conventional dosing, post dose level at
a prespecified time with extended-interval dosing) should be determined, particularly in critically ill
patients with serious infections or in disease states known to significantly alter aminoglycoside
pharmacokinetics (eg, cystic fibrosis, burns, or major surgery).
1. General dosing, severe, susceptible infections: IM, IV: 15 to 22.5 mg/kg/day
2. Meningitis:
a. Infants and Children: IV: 20 to 30 mg/kg/day
b. Adolescents: IV: 15 mg/kg/day
3. Cystic fibrosis: Infants, Children, and Adolescents: IV: 30–35 mg/kg/dose every 24 hours
4. Renal Impairment: IM, IV: Renally adjusted doses are based on doses of 15 to 22.5 mg/kg/day:
a. GFR >50 mL/minute/1.73 m2: No adjustment required
b. GFR 30 to 50 mL/minute/1.73 m2: Administer 10 to 15 mg/kg/day
c. GFR 10 to 29 mL/minute/1.73 m2: Administer 5 to 7.5 mg/kg/ day
d. GFR <10 mL/minute/1.73 m2: Administer 5 to 7.5 mg/kg every 48 to 72 hours
e. Intermittent hemodialysis: 5 mg/kg/dose; redose as indicated by serum concentrations
f. Peritoneal dialysis (PD): 5 mg/kg/dose; redose as indicated by serum concentrations
g. Continuous renal replacement therapy (CRRT): 15 mg/kg/day, monitor serum concentrations

Protocol Submitted by Clinical Pharmacist Rania Saad Mahmoud Ali

Supervisors: Prof. Dr. Mohamed Mahmoud Mohamed Abd El Latif, Prof. Dr. Maher Mokhtar Ahmed, Dr. Sahar Badr Hassan
11

PICU Empiric Antimicrobial Protocol for Patients with Severe Sepsis/Septic Shock Approved By: Prof. Dr. Azza Ahmed El-Tayeb
 Protocol for Submission of the partial fulfillment of the Master Degree in Pharmaceutical Sciences (Clinical Pharmacy)
Title: Clinical Outcomes of Prolonged versus Intermittent Infusion of Antibiotics in Critically ill Pediatric Patients with Sepsis at
Assiut University Children's Hospital

 Preparation for Administration

a. Parenteral: IV intermittent infusion: Dilute in a compatible solution (eg, NS, D5W) to a final
concentration of 0.25 to 5 mg/mL per the manufacturer; concentrations as high as 10 mg/mL have
been reported.
 Parenteral Administration:
a. IM: Administer undiluted into a large muscle mass. Slower absorption and lower peak concentrations,
probably due to poor circulation in the atrophic muscle, may occur following IM injection; in paralyzed
patients, suggest IV route
b. Intermittent IV infusion: Infuse over 30 to 60 minutes; in infants infusion over 1 to 2 hours is
recommended by the manufacturer.
 Storage/Stability:
a. Store intact vials at 20°C to 25°C. Following admixture at concentrations of 0.25 to 5 mg/mL in D5W,
NS, D51/4NS, D51/2NS, and LR, Amikacin is stable for 24 hours at room temperature, 60 days at 4°C, or
30 days at -15°C. Previously refrigerated or thawed frozen solutions are stable for 24 hours when
stored at 25°C.

 Fluconazole: Antifungal Agent, Systemic
1. Renal Impairment: For multiple dosing, administer usual load then adjust daily doses as follows;
based upon Schwartz calculations:
a. CrCl >50 mL/minute/1.73 m2: No adjustment necessary.
b. CrCl 10-50 mL/minute/1.73 m2 (no dialysis): Administer 50% of recommended dose at the normal
interval.
c. CrCl ≤10 mL/minute/1.73 m2: Administer 50% of recommended dose every 48 hours
d. Intermittent hemodialysis: Dialyzable (50%): May administer 100% of daily dose (according to
indication) after each dialysis session; others have suggested the following: Administer 50% of dose
every 48 hours; on dialysis days administer dose after dialysis session
e. Peritoneal dialysis: Administer 50% of recommended dose every 48 hours
f. Continuous renal replacement (CRRT): 6 mg/kg/dose every 24 hours
2. Hepatic Impairment: There are no dosage adjustments.
 Administration
 Oral: Administer without regard to meals; shake suspension well before use
 Parenteral: Do not use if cloudy or precipitated. Administered by IV infusion over approximately 1 to 2
hours at a rate not to exceed 200 mg/hour; in pediatric clinical trials, doses up to 8 to 10 mg/kg were
infused over 2 hours
 Storage/Stability
 Powder for oral suspension: Store dry powder at <30°C. Following reconstitution, store at 5°C to 30°C .
Discard unused portion after 2 weeks. Do not freeze.
 Injection: Store injection in glass at 5°C to 30°C. Store injection in plastic flexible containers with
overwrap at 20°C to 25°C. Do not freeze. Do not unwrap unit until ready for use.

Protocol Submitted by Clinical Pharmacist Rania Saad Mahmoud Ali

Supervisors: Prof. Dr. Mohamed Mahmoud Mohamed Abd El Latif, Prof. Dr. Maher Mokhtar Ahmed, Dr. Sahar Badr Hassan
12

PICU Empiric Antimicrobial Protocol for Patients with Severe Sepsis/Septic Shock Approved By: Prof. Dr. Azza Ahmed El-Tayeb
 Protocol for Submission of the partial fulfillment of the Master Degree in Pharmaceutical Sciences (Clinical Pharmacy)
Title: Clinical Outcomes of Prolonged versus Intermittent Infusion of Antibiotics in Critically ill Pediatric Patients with Sepsis at
Assiut University Children's Hospital

 Micafungin
1. Aspergillosis, Invasive
a. (4 months or older, 40 kg or less) 2 to 3 mg/kg IV once daily for at least 6 to 12 weeks
b. (4 months or older, more than 40 kg) 100 to 150 mg IV once daily for at least 6 to 12 weeks
2. Candidemia:
a. 2 mg/kg IV infusion over 1 hour once daily; MAX 100 mg/day
3. Candidiasis of the esophagus
a. (30 kg or less) 3 mg/kg IV infusion over 1 hour once daily
b. (greater than 30 kg) 2.5 mg/kg IV infusion over 1 hour once daily; MAX 150 mg/day
4. Invasive candidiasis
a. 2 mg/kg IV infusion over 1 hour once daily; MAX 100 mg/day
5. Hepatic and Renal Impairment:
a. There are no pediatric specific recommendations available; based on experience in adult patients, no
adjustment required; not dialyzable, supplemental dosing is not required following hemodialysis.
 Preparation for Administration
a. Parenteral: IV: Reconstitute with 5 mL of NS (preservative free) or D5W to each 50 or 100 mg vial
resulting in a concentration 10 mg/mL or 20 mg/mL, respectively. To minimize foaming, gently swirl to
dissolve; do not shake. Further dilution is dose dependent on patient age:
b. Pediatric patients: Dilute dose in NS or D5W to a final concentration of 0.5 to 4 mg/mL
c. Protect infusion solution from light (it is not necessary to protect the drip chamber or tubing from
light).
 Administration
a. Parenteral: IV: In pediatric patients, final concentrations >1.5 mg/mL should be administered via a
central line to minimize risk of infusion reactions. Prior to administration, flush line with NS. Infuse over
1 hour; more rapid infusions may result in a higher incidence of histamine-mediated reactions. Do not
coinfuse with other medications since precipitation may occur.
 Storage/Stability
a. Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Reconstituted and diluted
solutions in D5W or NS are stable for 24 hours at room temperature. Protect infusion solution from
light (it is not necessary to protect the drip chamber or tubing from light).

Protocol Submitted by Clinical Pharmacist Rania Saad Mahmoud Ali

Supervisors: Prof. Dr. Mohamed Mahmoud Mohamed Abd El Latif, Prof. Dr. Maher Mokhtar Ahmed, Dr. Sahar Badr Hassan
13

PICU Empiric Antimicrobial Protocol for Patients with Severe Sepsis/Septic Shock Approved By: Prof. Dr. Azza Ahmed El-Tayeb