Vancomycin, Ticarcillin, and Amikacin Compared with Ticarcillin-Clavulanate and Amikacin in the Empirical Treatment of Febrile, Neutropenic Children with Cancer

Abstract

We assessed two antibiotic regimens--vancomycin, ticarcillin, and amikacin, as compared with a vancomycin placebo, ticarcillin-clavulanate, and amikacin--as initial empirical therapy for febrile, neutropenic children with cancer. In a randomized, double-blind clinical trial, the planned 10-day treatment was unsuccessful in 15 percent of the vancomycin, ticarcillin, and amikacin group (n = 53), as compared with 38 percent of the group receiving ticarcillin-clavulanate and amikacin (n = 48) (P = 0.010). Of 10 episodes of breakthrough bacteremia, 9 (1 fatal) occurred in patients treated with ticarcillin-clavulanate and amikacin (P = 0.006). Each of the 10 microbial isolates was a gram-positive bacterium with similar susceptibilities to vancomycin and ticarcillin-clavulanate in vitro. Both regimens were well tolerated. None of the patients had detectable renal dysfunction, but those receiving vancomycin, ticarcillin, and amikacin were more likely to have twofold increases in serum hepatic-enzyme activity. Rashes consistent with the "red-man" syndrome occurred in three patients upon the infusion of vancomycin and in three others who received a placebo. We conclude that the combination of vancomycin, ticarcillin, and amikacin is more effective than ticarcillin-clavulanate and amikacin as empirical antibiotic therapy in clinical settings in which gram-positive bacteremias are a serious problem.

Vancomycin is not an essential component of the initial empiric treatment regimen for febrile neutropenic patients receiving ceftazidime: a randomized prospective study

“…It was particularly puzzling that 10 of the 33 were streptococcal species and could not be explained by the use of Hickman catheters. This shift also appears to be occurring in other institutions (8,16,17).…”

“…In 1983, we advocated the use of vancomycin as part of the initial regimen after a trial of ceftazidime monotherapy because we encountered several lethal gram-positive superinfections (12) and we subsequently showed that the addition of van-comycin to ceftazidime abrogated these superinfections (7). Other studies with different antibiotic combinations also supported the need for vancomycin as part of the initial regimen because of the increasing number of gram-positive infections that were being seen as well as for gram-positive superinfections which occurred during therapy (1,4,6,16). However, large studies done by the National Cancer Institute suggested that the addition of vancomycin can be delayed without any resulting increase in morbidity or mortality, even when a gram-positive infection is proven (11,13).…”

“…While the data from our prospective study examining the addition of vancomycin support a "stepped" approach, the other side of the coin, "front loading" with vancomycin, has been advocated for good reason. We and others have seen fatal gram-positive breakthrough bacteremia (6,12,16) and failure with gram-positive infections (3). More recently, fulminant alpha-hemolytic streptococcal infections have been seen in certain patients (8).…”

Effects of teicoplanin and those of vancomycin in initial empirical antibiotic regimen for febrile, neutropenic patients with hematologic malignancies. Gimema Infection Program

“…Teicoplanin, an antibiotic administered once daily with activity against strains of enterococci resistant to vancomycin, seems to be less toxic (13,21) and is easier to administer. Both vancomycin (12,22) and teicoplanin (4, 14,16), when used in initial, combined therapy, have proved to be efficacious in the treatment of neutropenic patients with gram-positive bacteremias; however, comparative studies able to establish which glycopeptide antibiotic may be the better choice in febrile, neutropenic patients are lacking.…”

How should imipenem-cilastatin be Used in the treatment of fever and infection in neutropenic cancer patients?

“…The initial use of vancomycin as part of empiric antibiotic regimens is usually recommended for adequate coverage of infections caused by gram positive organisms that are resistant to ␤-lactam antibiotics. 20 However, Rolston et al 3 reported that adding vancomycin within 48 hours of the onset of fever or infection in patients with gram positive infections was not superior to its introduction or the introduction of other antibiotics (trimethoprim plus sulfamethoxazole, clindamycin, or nafcillin) later in the course of the infection. In that study, the majority of patients who did not respond to the initial regimen responded to other antibacterial therapy.…”