The Rodney Dangerfield Syndrome - American Society of Health ...

Continuous Infusion Antibiotics
The Rodney Dangerfield Syndrome
“Gets no respect”
Kevin J. Chapple, Pharm.D., BCPS
Clinical Pharmacist
Shore Health System
University of Maryland Medical System
Easton, MD

Time-Dependent Killing
(TDK)
• Keep serum level above MIC
• Penicillins
• Cephalosporins
• Vancomycin
• Carbapenems
• Monobactams
• Clindamycin
• Linezolid
• Macrolides

Concentration-Dependent
Killing (CDK)
• Efficacy of killing of bacteria is
enhanced with higher peaks,
regardless of trough
• Aminoglycosides
• Fluoroquinolones
• Continuous infusion antibiotics are
NOT typically considered for
antimicrobials that exhibit CDK.

0 4 8 12 16 24
Time (hours)
Intermittent
Continuous
Minimum Inhibitory Concentration

Continuous Infusion
• Keep serum concentrations above
MIC at all times
• Takes advantage of TDK
• Possible cost advantage
• May be able to use less drug per day
compared to intermittent dosing.

In the Literature…
• Ceftazidime
• Febrile neutropenia
• Pulmonary Infections
• Piperacillin/tazobactam
• Intra-abdominal infections
• Pulmonary Infections
• Vancomycin
• Osteomyelitis
• General Critical Infections
• Cefepime
• Pulmonary
• General Critical Infections

Dosing
• Most trials use same daily dose
• However, may be feasible to use
lower daily doses in many cases
• Potential cost savings
• Less exposure to high peaks
• May minimize adverse effects
• High peaks NOT needed for antimicrobials
that exhibit TDK

Stability
• One of the biggest concerns from a
theoretical standpoint
• Some literature on most of the
aforementioned antimicrobials
• Most stable in solution for 12-24 hours

Summary - Advantages
• Acquisition cost savings
• Less nursing and pharmacy time
• Take full advantage of
pharmacodynamic principles
• Avoid high peaks
• No clinical advantage to high peaks with
antimicrobials that work on cell wall
• ? Avoidance of some adverse effects

Summary - Disadvantages
• May need additional IV access
• Stability
• Most relevant antibiotics not an issue
• Possible increase in other ADR’s
• Line sepsis
• Thrombophlebitis

Conclusions
• File it in your mind!!
• Complicated patients
• Known or suspected intermediate sensitivity
• Endocarditis, Osteomyelitis, Meningitis, Cystic
Fibrosis
• Vancomycin CI Kinetics very interesting in
meningitis
• Literature would support use in:
• complicated pneumonia
• intra-abdominal infections
• infections in critically ill

Brushing Up…
• Kasiakou SK, Sermaides GJ, Michalopoulos A, Soteriadis ES,
Falagas ME. Continuous versus intermittent administration of
antibiotics: a meta-analysis of randomised controlled clinical
trials. Lancet Infect Dis 2005;5:581-9.
• Benko AS, Cappelletty DM, Kruse JA, Rybak MJ. Continuous
infusion versus intermittent administration of ceftazidime in
critically ill patients with suspected gram-negative infections.
Antimicrob Agents Chemother 1996; 40: 691–5.
• Di Filippo A, De Gaudio AR, Novelli A, et al. Continuous infusion
of vancomycin in methicillin-resistant staphylococcus infection.
Chemotherapy 1998; 44: 63–8.
• Hanes SD, Wood GC, Herring V, et al. Intermittent and
continuous ceftazidime infusion for critically ill trauma patients.
Am J Surg 2000; 179: 436–40.
• Jaruratanasirikul S, Sriwiriyajan S, Ingviya N. Continuous
infusion versus intermittent administration of cefepime in
patients with Gram-negative bacilli bacteraemia. J Pharm
Pharmacol 2002; 54:1693–6.

Brushing Up…
• Nicolau DP, McNabb J, Lacy MK, Quintiliani R, Nightingale CH.
Continuous versus intermittent administration of ceftazidime in
intensive care unit patients with nosocomial pneumonia. Int J
Antimicrob Agents 2001; 17: 497–504.
• Wysocki M, Delatour F, Faurisson F, et al. Continuous versus
intermittent infusion of vancomycin in severe staphylococcal
infections: prospective multicenter randomized study. Antimicrob
Agents Chemother 2001; 45: 2460–7.
• Florea NR, Kotapati S, Kuti JL, Geissler EC, Nightingale CH, Nicolau
DP. Cost analysis of continuous versus intermittent infusion of
piperacillin-tazobactam: a time-motion study. Am J Health Syst
Pharm 2003; 60: 2321–7.
• Grant EM, Kuti JL, Nicolau DP, Nightingale C, Quintiliani R. Clinical
efficacy and pharmacoeconomics of a continuous-infusion
piperacillin-tazobactam program in a large community teaching
hospital. Pharmacotherapy 2002; 22: 471–83.
• Hitt CM, Nightingale CH, Quintiliani R, Nicolau DP. Cost comparison
of single daily i.v. doses of ceftriaxone versus continuous infusion of
cefotaxime. Am J Health Syst Pharm 1997; 54: 1614–18.

Brushing Up…
• Mac Gowan AP, Bowker KA. Continuous infusion of beta lactam
antibiotics. Clin Pharmacokinet 1998; 35: 391-402.
• Alou L, Aguilar L, Sevillano D, Gimenez MJ, Echeverria O, Gomez-
Lus ML, Prieto J. Is there a pharmacodynamic need for the use
of continuous versus intermittent infusion with ceftazidime
against pseudomonas aeruginosa? An in vitro pharmacodynamic
model. JAC 2005; 55;209-13.
• Nicolau DP, Nightengale CH, Banevicius MA, Fu Q, Quintiliani R.
Serum bactericidal activity of ceftazidime: continuous infusion
versus intermittent injections. Antimicrob Agents Chemother
1996;40:61-4.
• Albanese J, Leone M, Bruguerolle B, Ayem ML, Lacarelle B, Martin
C. Antimicrob Agents Chemother 2000;44:1356-8.
• Jacqueline C, Batard E, Perez R, Boutoille D, Hamel A, Caillon J,
Kergueris MF, Potel G, Bugnon D. Antimicrob Agents Chemother
2002;46:3706-11.