Multicenter, randomized trial of ciprofloxacin plus azlocillin versus ceftrazidime plus amikacin for empiric treatment of febrile neutropenic patients

Flaherty, John P.; Waitley, David; George, Donna L.; Arnow, Paul M.; O’Keefe, Paul; Weinstein, Robert A.

doi:10.1016/0002-9343(89)90080-6

Cited by 53 publications

(26 citation statements)

References 15 publications

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“…The efficacy of regimens containing ciprofloxacin and various antipseudomonal ␤-lactams has previously been demonstrated (11,13,18); therefore, the focus of this study was not to demonstrate the efficacy of quinolone-containing regimens or the superiority of combination regimens over single-agent therapies. Rather, our objective was to determine whether the bactericidal advantage noted for ciprofloxacin monotherapy over ofloxacin against P. aeruginosa persisted when these agents were utilized in combination with an antipseudomonal ␤-lactam.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to the aminoglycosides, the combination of an antipseudomonal ␤-lactam with ciprofloxacin deters the development of resistance and may interact synergistically in vitro against some strains of P. aeruginosa (3-6, 8, 14, 15, 19). Clinical efficacy of fluoroquinolone-␤-lactam combinations for empiric therapy has been demonstrated in a limited number of clinical trials (11,13,18).As monotherapy, ciprofloxacin is significantly more active against P. aeruginosa than ofloxacin. It appears, however, that the role of the fluoroquinolones in the treatment of pseudomonal infections lies in their combination with antipseudomonal ␤-lactams such as ceftazidime or piperacillin.…”

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confidence: 99%

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Comparison of the bactericidal activities of ofloxacin and ciprofloxacin alone and in combination with ceftazidime and piperacillin against clinical strains of Pseudomonas aeruginosa

Klepser

Patel

Nicolau

et al. 1995

Antimicrob Agents Chemother

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On the basis of MIC data, ciprofloxacin exhibits superior activity against Pseudomonas aeruginosa than the other currently available fluoroquinolones do. Despite the antipseudomonal advantage noted for ciprofloxacin monotherapy, it is unknown whether this advantage is maintained when the fluoroquinolones are used in combination with antipseudomonal ␤-lactams such as ceftazidime and piperacillin. Twelve healthy volunteers were enrolled in this open-label, randomized, steady-state, six-way cross-over, comparative trial. All subjects received the following regimens: (i) 400 mg of ofloxacin given intravenously (i.v.) every 12 h (q12h), (ii) 400 mg of ciprofloxacin given i.v. q12h, (iii) 400 mg of ofloxacin given i.v. q12h plus 1 g of ceftazidime given i.v. every 8 h (q8h), (iv) 400 mg of ciprofloxacin given i.v. q12h plus 1 g of ceftazidime given i.v. q8h, (v) 400 mg of ofloxacin given i.v. q12h plus 4 g of piperacillin given i.v. q8h, and (vi) 400 mg of ciprofloxacin given i.v. q12h plus 4 g of piperacillin given i.v. q8h. Serum bactericidal titers with subsequent calculation of the area under the bactericidal curve were determined against three clinical isolates of P. aeruginosa. As monotherapy, ciprofloxacin demonstrated superior antipseudomonal activity than ofloxacin did; however, combination of these agents with ceftazidime yielded remarkably similar and statistically comparable activity profiles. In contrast, ciprofloxacin-piperacillin retained a bactericidal advantage over ofloxacin-piperacillin. Although ciprofloxacin exhibits superior antipseudomonal activity when used as monotherapy, combination of ofloxacin or ciprofloxacin with ceftazidime yielded equivalent activity profiles against susceptible strains of P. aeruginosa.Pseudomonas aeruginosa is a problematic pathogen associated with numerous nosocomial and community-acquired infections. Treatment of infections caused by this microbe is frequently complicated by an intrinsic resistance to numerous antimicrobial agents and by the frequent development of resistance during single-agent therapy. Troublesome resistance profiles coupled with the significant morbidity and mortality associated with pseudomonal infections have prompted many clinicians to utilize combinations of antimicrobial agents to treat infections caused by this pathogen. Historically, combination therapy has consisted of an antipseudomonal ␤-lactam, such as ceftazidime or piperacillin, plus an aminoglycoside. However, the potential for toxicity and the need for parenteral administration have encouraged clinicians to search for therapeutic alternatives to the aminoglycosides.The fluoroquinolones ciprofloxacin and ofloxacin both display in vitro and in vivo activity against P. aeruginosa; however, ciprofloxacin has been reported to be severalfold more active against this microorganism than ofloxacin (10,19,20). Typical MICs of ciprofloxacin and ofloxacin for 90% of P. aeruginosa isolates range from 0.25 to 0.5 g/ml (10, 19) and 2.0 to 4.0 g/ml (10, 20), respectively. However, despite low init...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Comparison of the bactericidal activities of ofloxacin and ciprofloxacin alone and in combination with ceftazidime and piperacillin against clinical strains of Pseudomonas aeruginosa

Klepser

Patel

Nicolau

et al. 1995

Antimicrob Agents Chemother

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“…Some have been used for infection prevention and for the treatment of established infections in neutropenic cancer patients (2,6,10,15). More recently, broad-spectrum quinolones such as ciprofloxacin, which are available for parenteral and oral administration, have made it possible to shorten the duration of antibiotic administration to febrile cancer patients in the hospital by facilitating the early discharge of such patients on oral antibiotic therapy (3). Certain low-risk neutropenic patients have even been treated as outpatients during the entire febrile episode (12).…”

mentioning

confidence: 99%

“…Agents such as norfloxacin and ciprofloxacin are used in most large cancer treatment centers for antimicrobial prophylaxis in high-risk patients with prolonged neutropenia, including patients with acute leukemia and recipients of bone marrow transplantations (2,4,15). Ciprofloxacin has also been used in combination with various agents (aminoglycosides, beta-lactams, vancomycin, and clindamycin) for the treatment of febrile episodes in neutropenic patients, both in the hospital and in an ambulatory care setting (1,3,10,12,13). Aniong the currently available quinolones, ciprofloxacin is the most potent, particularly against gram-negative bacilli, including Pseuydomonas aeruginosa, and any promising newer agents belonging to this class need to be compared with ciprofloxacin.…”

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Susceptibilities of bacterial isolates from patients with cancer to levofloxacin and other quinolones

Dholakia

Rolston

et al. 1994

Antimicrob Agents Chemother

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The antibacterial activity of levofloxacin was compared with those of ofloxacin and ciprofloxacin against bacterial isolates from patients with cancer. In general, levofloxacin was as active or was twofold more active than ofloxacin and was two-to fourfold less active than ciprofloxacin against most gram-negative pathogens. Against Pseudomonas aeruginosa, ciprofloxacin was the most active agent tested (MIC for 90% of isolates tested, 1.0 jig/ml). Overall, all three agents had similar activities against gram-positive organisms and were moderately active against methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci, Streptococcus species, and Enterococcus species.During the past decade a large number of newer quinolones have been developed. Most of these agents, including norfloxacin, ciprofloxacin, ofloxacin, lomefloxacin, and fleroxacin, have broader antimicrobial spectra and improved bioavailabilities in comparison with those of naladixic acid (16). Some have been used for infection prevention and for the treatment of established infections in neutropenic cancer patients (2, 6, 10, 15). More recently, broad-spectrum quinolones such as ciprofloxacin, which are available for parenteral and oral administration, have made it possible to shorten the duration of antibiotic administration to febrile cancer patients in the hospital by facilitating the early discharge of such patients on oral antibiotic therapy (3). Certain low-risk neutropenic patients have even been treated as outpatients during the entire febrile episode (12). These newer applications have widened the scope of the quinolones as antibacterial agents. However, the widespread prophylactic and therapeutic usage of quinolones in neutropenic cancer patients has raised concern about the emergence of resistance to them and a reduction in their overall impact as clinically useful antibiotics.Ofloxacin exists as two optically active isomers because of the asymmetric center at C-3 of the oxazine ring, and levofloxacin (l-ofloxacin) is the more active isomer (4,5,14 796-8578. Anderson Cancer Center at Houston during the past 5 years. The majority (>90%) of these isolates were from blood culture specimens, and the rest were from various clinical sources including sputum, wounds, urine, bile, and cerebrospinal fluid. Many isolates came from patients who had received cephalosporins, penicillins, carbapenems, monobactams, and quinolones for therapy or prophylaxis. Only one isolate per patient was used for testing in order to avoid duplication. Staphylococcus aureus and Staphylococcus epidermidis isolates were considered penicillin G susceptible on the basis of an MIC of <0.1 ,ug/ml, methicillin susceptible on the basis of an MIC of s4.0 ,ug/ml, and methicillin resistant on the basis of an MIC of .8.0 ,tg/ml.Susceptibility testing was performed in accordance -with the guidelines established by the National Committee for Clinical Laboratory Standards by using a previously described microtiter broth dilution method (8,11). Briefly, orga...

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Ciprofloxacin plus piperacillin is an equally effective regimen for empiric therapy in febrile neutropenic patients compared with standard therapy

et al. 1998

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The purpose of this study was to test the comparative efficacy and toxicity of empiric gentamicin and ciprofloxacin, in combination with piperacillin, in febrile patients with treatment-induced neutropenia. Fifty patients were prospectively randomized to receive piperacillin plus gentamicin (PG), and 46 were randomized to receive piperacillin plus ciprofloxacin (PC). The groups were similar in age, sex, diagnosis, duration of neutropenia, and incidence of positive cultures. The two antibiotic regimens were associated with comparable rates of defervescence in the patients with gram-positive bacteremia. In the patients with gram-negative bacteremia and those with negative cultures, however, defervescence was more prompt in the PC group. In particular, 27% of the culture-negative patients on PC, compared to only 5% of those on PG, defervesced within 72 hr (P = 0.015). Because of the more prompt defervescence in the PC group, amphotericin B was used less frequently; 78% of the patients on PG compared with only 56% of those on PC were started on amphotericin B (P = 0.025). PC is an effective alternative to the more traditional PG for treatment of febrile neutropenic hosts who have not been given prophylactic quinolones. More important, PC appears to hasten defervescence compared with PG, especially in culture-negative patients and those with gram-negative bacteremia, and may decrease the necessity of additional antimicrobial agents such as amphotericin B.

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Multicenter, randomized trial of ciprofloxacin plus azlocillin versus ceftrazidime plus amikacin for empiric treatment of febrile neutropenic patients

Cited by 53 publications

References 15 publications

Comparison of the bactericidal activities of ofloxacin and ciprofloxacin alone and in combination with ceftazidime and piperacillin against clinical strains of Pseudomonas aeruginosa

Comparison of the bactericidal activities of ofloxacin and ciprofloxacin alone and in combination with ceftazidime and piperacillin against clinical strains of Pseudomonas aeruginosa

Susceptibilities of bacterial isolates from patients with cancer to levofloxacin and other quinolones

Ciprofloxacin plus piperacillin is an equally effective regimen for empiric therapy in febrile neutropenic patients compared with standard therapy

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