What is the appropriate use of intravenous (IV) ticarcillin with vancomycin in an adult or pediatric patient with a severe, complicated infection?

Ticarcillin with Vancomycin: Compatibility and Clinical Use

Do not administer ticarcillin and vancomycin through the same intravenous line or mix them together, as they are physically incompatible and will precipitate. 1

Critical Compatibility Issue

• Vancomycin solution has a low pH and causes physical instability when mixed with beta-lactam antibiotics, including ticarcillin. 1
• Mixtures of vancomycin and beta-lactam antibiotics have been demonstrated to be physically incompatible, with the likelihood of precipitation increasing at higher vancomycin concentrations. 1
• The intravenous lines must be adequately flushed between administration of these antibiotics. 1
• It is recommended to dilute vancomycin solutions to 5 mg/mL or less to minimize precipitation risk when sequential administration is necessary. 1

Clinical Context for Combined Use

While these agents cannot be mixed, they may be used concurrently (via separate lines) in specific clinical scenarios:

Empirical Therapy in Febrile Neutropenic Patients

• The combination of vancomycin, ticarcillin, and amikacin demonstrated superior efficacy compared to ticarcillin-clavulanate and amikacin in febrile, neutropenic children with cancer, with treatment failure rates of 15% versus 38% respectively (P = 0.010). 2
• This regimen was particularly effective in preventing breakthrough gram-positive bacteremia, with 9 of 10 breakthrough bacteremias occurring in the group without vancomycin (P = 0.006). 2
• Both regimens were well tolerated, though vancomycin-containing regimens showed higher rates of transient hepatic enzyme elevation. 2

Serious MRSA Infections Requiring Gram-Negative Coverage

• For serious MRSA infections (bacteremia, endocarditis, osteomyelitis, meningitis, pneumonia, necrotizing fasciitis), vancomycin 15-20 mg/kg IV every 8-12 hours with target trough concentrations of 15-20 μg/mL is recommended. 3
• If concurrent gram-negative coverage is needed, ticarcillin can be administered separately, but addition of gentamicin or rifampin to vancomycin for MRSA bacteremia or native valve endocarditis is not recommended. 3

Vancomycin Dosing When Used Concurrently

• For seriously ill patients with suspected MRSA infection, administer a loading dose of 25-30 mg/kg (actual body weight). 4, 5
• Prolong the infusion time to 2 hours and consider antihistamine premedication to prevent red man syndrome with loading doses. 3
• Obtain trough concentrations at steady state, before the fourth or fifth dose, to guide dosing adjustments. 3, 4
• For patients with normal renal function, standard dosing is 15-20 mg/kg every 8-12 hours, not to exceed 2 g per dose. 3, 1

Administration Protocol

• Administer vancomycin at no more than 10 mg/min or over at least 60 minutes, whichever is longer. 1
• Vancomycin concentrations should not exceed 5 mg/mL in most patients; concentrations up to 10 mg/mL may be used in fluid-restricted patients but increase infusion-related event risk. 1
• Ticarcillin should be administered via a separate IV line with adequate line flushing between antibiotic administrations. 1

Common Pitfalls to Avoid

• Never mix vancomycin and ticarcillin in the same solution or administer through the same line without flushing—precipitation will occur. 1
• Do not use combination therapy with vancomycin and other antibiotics for MRSA infections without clear evidence of benefit, as published data are inconsistent and some regimens have known toxicities. 6
• Monitor for nephrotoxicity when vancomycin is combined with other potentially nephrotoxic agents, as trough levels >15 mg/L significantly increase this risk. 5