Double Beta-lactam Research Articles

Adverse Events Comparison of Double Beta-Lactam Combinations for Bloodstream Infections: Ampicillin plus Ceftriaxone and Ampicillin/Cloxacillin.

In Japan, only ampicillin/cloxacillin (ABPC/MCIPC) is available as an anti-staphylococcal penicillin-based treatment for Staphylococcus aureus bacteremia. However, the incidence of adverse events associated with double beta-lactam administration remains unknown. Therefore, we investigated the adverse events of double beta-lactam administration in patients with bacteremia. Adult patients (≥18 years) with bacteremia treated with ABPC, ABPC + ceftriaxone (CTRX), or ABPC/MCIPC were retrospectively analyzed. The primary outcome of this study was the incidence of adverse events such as acute kidney injury, liver dysfunction, and myelosuppression. Chi-square tests and t-tests were used for bivariate analysis. Propensity score (PS) matching was conducted to adjust for confounding factors. We included 277 ABPC-, 57 ABPC + CTRX-, and 43 ABPC/MCIPC-treated patients. Significant differences were noted in age, number of male patients, proportion of patients with qSOFA score ≥2, incidence of chronic kidney disease, treatment duration, mechanical ventilation use, vasopressor use, and proportion of patients with acute kidney injury (AKI) KDIGO grade ≥2. Further, a significant difference was observed between ABPC and ABPC/MCIPC, with a hazard ratio of 1.83 in AKI. In the PS-matched cohort, AKI incidence associated with ABPC/MCIPC was significantly higher than that associated with ABPC. ABPC + CTRX may be safe, whereas ABPC/MCIPC presents a higher risk of AKI and may not be suitable.

370. The comparison of adverse events in combination with double beta-lactam antimicrobials: Ampicillin plus Ceftriaxone and Ampicillin/Cloxacillin with bloodstream infections

Abstract Background Double beta-lactams are used to treat infective endocarditis, but the incidence rate of adverse events is unclear. We aimed to compare the incidence rates of adverse events of ampicillin(ABPC) versus ABPC plus ceftriaxone(CTRX) and ABPC/MPIPC(cloxacillin). Methods We retrospectively included adult bacteremia patients admitted to St. Luke's International Hospital and received ABPC, ABPC plus CTRX, and ABPC/MPIPC between 2004 and 2022. We excluded patients on hemodialysis, those with missing data, those who used more than three beta-lactam antimicrobials, and beta-lactam other than ABPC, CTRX, or ABPC/MPIPC. All statistical analysis was done using IBM SPSS. Results We included 280, 59, and 43 patients for ABPC, ABPC plus CTRX, and ABPC/MPIPC, respectively. There were significant differences in median age(70.8 [standard deviation: SD 16.6], 64.3[16.7], 56.6[17.5]), male sex(62.1%, 47.5%, 72.1%), qSOFA ≥2 (23.1%, 64.4%, 41.9%), admission in an intensive care unit(6.4%, 40.7%, 14.0%), mechanical ventilation (5.4%, 23.7%, 20.9%), use of vasopressor (10.4%, 32.2%, 23.3%), administration of vancomycin (7.5%, 27.1%, 41.9%) or clindamycin (19.6%, 23.7%, 44.2%) for more than three days, hepatic dysfunction (AST: 42.6[81.5], 120.4[493.0], 54.1[68.5], ALT: 33.1[35.9], 98.2[380.0], 46.6[67.6], anemia(Hgb: 10.8[2.1], 11.6[2.4], 11.9[2.8] and thrombocytopenia (PLT: 203.5[105.0], 154.8[115.0], 255.9[159.7]) on admission. There were significant differences in AKI (9.0%, 12.3%, 30.2%), treatment duration (13.9 [12.1] days, 9.1 [8.7] days 29.0 (19.2) days, and duration of hospitalization 34.1[31.1] days, 48.3 [50.4] days, 51.6 [32.5] days, but no difference in 30 days mortality (4.3%, 6.8%, 2.3%) and 90 days mortality (8.2%, 13.6%, 7.0%). Kaplan-Meier analysis showed no significant difference between ABPC and CTRX plus ABPC in AKI, but there was a significant difference between ABPC and ABPC/MPIPC(figure 1, 2). The hazard ratio of ABPC/MPIPC for AKI was 1.572(95% confidence interval, 1.067-2.315)(figure 3).Figure 1Percent of non-AKI between ABPC and ABPC plus CTRXAbbreviation: AKI, acute kidney injury; ABPC, ampicillin; CTRX, ceftriaxoneFigure 2Percent of non-AKI between ABPC and ABPC/MPIPCAbbreviation: AKI, acute kidney injury; ABPC, ampicillin; MPIPC, cloxacillin Conclusion Double beta-lactam therapy with ABPC plus CTRX may be relatively safe, but careful follow-up is needed for platelet count and hepatic function. On the other hand, ABPC/MPIPC has a significantly higher incidence of AKI compared to other antimicrobials. Factors associated with AKI Abbreviation: AKI, acute kidney injury; ABPC, ampicillin; MPIPC, cloxacillin; CI, coincidence interval Disclosures All Authors: No reported disclosures

Ampicillin Plus Ceftriaxone Regimen against Enterococcus faecalis Endocarditis: A Literature Review.

Enterococcus faecalis infective endocarditis (EFIE) continues to represent a potentially fatal infectious disease characterized by elevated morbidity and mortality. Despite advances in antimicrobial therapy, changing demographics and the reduced availability of useful antibiotics combined with the dissemination of multi-drug resistant strains, the mortality rate remained unchanged in the last decades. Nowadays, optimizing the antibiotic regimen is still of paramount importance. Historically, aminoglycosides were considered as a cornerstone for treatment even though their use is associated with a high risk of kidney failure. It is against this background that, in recent years, several studies have been carried in order to assess the validity of alternative therapeutic approaches, including combinations of beta-lactams, that, acting synergistically, have yielded useful results in different clinical settings. In this scenario, we searched and critically report clinical studies assessing the efficacy and safety of double beta-lactam therapy in treating EFIE.

Effectiveness of the antibiotic combinations for enterococcal infections treatment: a critical review

During the last decades, enterococci have emerged as important etiological agents in bacteremia, osteomyelitis, endocarditis and soft tissue infections. Antimicrobial combinations have been the most used therapeutic strategies for these infections, aiming for a bactericidal synergistic effect. However, besides in vitro and in vivo models, the clinical usefulness of such combinations is controversial, especially in non-endocardic systemic infections. For example, although beta-lactam and aminoglycoside combinations or double beta-lactam treatment have achieved high cure rates in endocarditis, the optimal treatment has not yet been clarified or if these combinations are useful in other infections. The aim of this review was to analyze and summarize the results from several experimental models of antienterococcal combined therapy and from clinical trials available in PubMed/Medline, to better assess the evidence that supports the use of these combinations. In conclusion, the available information is scarce, and more and better in vivo models and clinical studies are required to confirm the potential synergistic activity of antienterococcal combinations.

Success of ampicillin plus ceftriaxone rescue therapy for a relapse of Enterococcus faecalis native-valve endocarditis and in vitro data on double beta-lactam activity

We report a patient with Enterococcus faecalis native-valve endocarditis who relapsed after 4 weeks of treatment with ampicillin plus gentamicin. The relapse was cured with ampicillin plus ceftriaxone, which was introduced after gentamicin-induced acute renal failure. This double beta-lactam combination showed a bactericidal effect in time-killing curve studies.

Beta-Lactam Antibiotic Therapy in Febrile Granulocytopenic Patients

To compare the efficacy, toxicity, and cost-effectiveness of double beta-lactam therapy with monotherapy. A randomized, controlled trial. Febrile, granulocytopenic patients (429). Patients were randomly assigned to receive iv cefoperazone (3 g every 12 hours) plus piperacillin (75 mg/kg body weight every 6 hours), ceftazidime (2 g every 8 hours) plus piperacillin (75 mg/kg every 6 hours), or imipenem alone (1.0 g or 0.5 g every 6 hours). Patients also received prophylactic vitamin K. Clinical improvement, eradication of the infecting organism, and toxicity in 403 evaluable patients with one or more infections. Cefoperazone and ceftazidime, when given in combination with piperacillin, were equally effective (response rates of 75% (104 of 138 patients) and 74% (101 of 137 patients), respectively). Monotherapy with imipenem had a response rate of 82% (111 of 136 patients) and was as effective as double beta-lactam therapy. Overall antibiotic-related toxicity was minimal, although seizures were associated with high doses of imipenem. Seizures occurred in 3 of 29 patients (10.3%) who were receiving 4 g/d of imipenem, in 3 of 136 patients (2.2%) who were receiving cefoperazone plus piperacillin, in 0 of the 132 patients who were receiving ceftazidime plus piperacillin, and in 1 of 106 patients (0.9%) who were receiving 2 g/d of imipenem (P less than 0.005). The 2-g daily dose of imipenem was as effective as the 4-g daily dose. Diarrhea was more frequent in patients receiving cefoperazone, whereas nausea occurred more often with imipenem. No antibiotic-related hemorrhage or nephrotoxicity was observed. Superinfections caused by beta-lactam-resistant, gram-negative bacilli were uncommon but occurred more frequently with double beta-lactam therapy than with imipenem monotherapy (11 of 268 patients compared with 1 of 135 patients; P = 0.06). Xanthomonas maltophilia superinfections occurred only in patients receiving imipenem (3 of 135 patients compared with 0 of 268 patients; P = 0.03). Imipenem monotherapy was the least expensive therapy. Cefoperazone and ceftazidime were equally effective when used in combination antibiotic therapy with piperacillin. Twice-daily cefoperazone is less expensive than ceftazidime given three times daily. Monotherapy with imipenem, at a daily dose of 2 g, is as efficacious as double beta-lactam therapy and costs less than combination therapy.

Antibiotic Therapy for Gram-negative Bacteremia

Although antibiotic therapy is the mainstay of therapy for gram-negative bacillary bacteremia, the amelioration of the underlying conditions, the correction of predisposing factors, the drainage of abscesses, the removal of infected foreign bodies, and adequate supportive care are also of paramount importance for curing the infection and should not be neglected. Beginning in the late 1960s, most of the clinical work on gram-negative infections has focused on the evaluation of new antibiotics. Numerous studies have shown that early, appropriate antibiotic treatment of gram-negative bacteremia significantly improved patients' outcomes and prevented the development of septic shock. Prescribing standard doses of antibiotics does not necessarily mean that therapeutic levels will be reached in all patients, and relapses of infections or breakthrough bacteremias can occur in patients with subinhibitory serum levels of antibiotics. The monitoring of serum concentrations of antibiotic is therefore recommended in critically ill septic patients. Whereas initial studies on the antibiotic treatment of gram-negative bacteremia were carried out in nonneutropenic patients, more recent clinical investigations have been performed almost exclusively in cancer patients with neutropenia. Studies conducted in the 1970s and 1980s among these patients have shown the following: (1) early empirical therapy reduced the mortality of gram-negative bacteremia; (2) therapy with a combination of two antibiotics, be it an extended spectrum penicillin plus an aminoglycoside or a third-generation cephalosporin, has significantly improved patients' outcomes; and (3) triple-drug combinations (i.e., a penicillin plus a cephalosporin plus an aminoglycoside) are not superior to combinations of beta-lactams and aminoglycosides. For the treatment of gram-negative bacteremia, clinicians today have a choice between well-established antibiotic combinations and broad-spectrum single-agent therapy with third-generation cephalosporins or carbapenem antibiotics. Although recent studies suggested that monotherapy could be as effective as combination therapy for the empirical treatment of fever in the neutropenic host, no definitive study has so far unquestionably demonstrated the equivalence of these treatments in patients with gram-negative bacteremias, especially those caused by P. aeruginosa, or in patients with adverse prognostic conditions, such as persistent and profound granulocytopenia. This literature should however be reviewed with great caution. Indeed, only a minority of studies have included a sufficient number of patients to confidently assess the impact of therapy on patients' outcomes. Obviously, small studies can have a significant risk of type II errors, that is, making false-negative conclusions.(ABSTRACT TRUNCATED AT 400 WORDS)

Overview of Synergy with Reference to Double Beta-Lactam Combinations

Combination antimicrobial therapy is used to expand the bacterial coverage over a single agent, to prevent the emergence of resistant organisms, to decrease toxicity by allowing lower doses of both agents, or for synergy. Synergy is one of the most common of these reasons, especially in serious infections. The introduction of new broad-spectrum beta-lactam antimicrobials has led to their combination in the treatment of seriously ill patients. Whereas a combination of an aminoglycoside and a beta-lactam antimicrobial is frequently synergistic, much less is known about synergy between combinations of beta-lactams. In vitro testing shows most combinations of two beta-lactams to be indifferent or additive in their effects; rarely does synergy occur. Antagonism can sometimes be seen, particularly with combinations involving cefoxitin or imipenem, especially if the treated organism is Enterobacter or Pseudomonas. Results of clinical trials comparing double beta-lactam (DBL) therapy with aminoglycoside/beta-lactam combinations show no difference in clinical response rates. Highly active DBL combinations may substitute for standard aminoglycoside-containing regimens in certain situations, even though they are not reliably synergistic. However, in the treatment of seriously ill patients such combinations may be less desirable.

Double beta lactam combinations may replace conventional therapy in serious bacterial infections

Double beta lactam combinations may replace conventional therapy in serious bacterial infections

Aztreonam-Flucloxacillin Double Beta-lactam Treatment as Empirical Therapy of Serious Infections in Very Elderly Patients

Aztreonam, the first monocyclic beta-lactam antibiotic with pure anti-Gram-negative activity, combined with flucloxacillin, a penicillinase resistant penicillin, was given as empirical treatment of 53 serious infections in very elderly people. Eighteen of the cases had positive blood cultures and 11 had a clinical picture of sepsis without positive blood cultures: Of 49 evaluable infections, 45 (92%) were cured. In 40% of the infections, antibiotic treatment could be narrowed after 72 hours to one antibiotic. Diarrhoea, mostly transitory, was the only side-effect. Aztreonam-flucloxacillin combination is a safe and effective empirical treatment regimen for serious infections in very elderly patients.

Ceftriaxone versus aztreonam plus cefazolin for infections in cancer patients with adequate neutrophil counts

In a prospective randomized trial, 154 febrile episodes in cancer patients with adequate neutrophil counts (greater than 1,000 cells/mm3) were treated with either ceftriaxone (72 episodes) or aztreonam plus cefazolin (82 episodes). Documented infections represented almost half of the febrile episodes. The overall response rates among the 144 evaluable episodes were similar for the two regimens: 76% (51/67) with ceftriaxone versus 82% (63/77) with aztreonam plus cefazolin (p = 0.41, not significant). Although not statistically significant, the response rate of the microbiologically documented infections was slightly better in patients treated with the double beta-lactam combination (85% vs. 65%, p = 0.16) and clinically documented infections showed a better response in the group of patients receiving monotherapy (87% vs. 59%, p = 0.12). No serious adverse effects were observed during this study and both regimens were well tolerated. Ceftriaxone or the combination of aztreonam plus cefazolin showed a similar efficacy as empirical therapy for infections in cancer patients with adequate neutrophil counts.

Interventional Antimicrobial Strategy in Febrile Neutropenic Patients

In a prospective, randomized multicenter trial of the Paul Ehrlich society different concepts for sequential empirical antimicrobial strategy for the treatment of patients with neutropenia less than 1.0/nl and fever greater than 38.5 degrees C and/or documented infection were studied. In phase I, patients with unexplained fever (FUO) were randomized for the combination of acylaminopenicillin plus aminoglycoside or third-generation cephalosporin plus aminoglycoside or double beta lactam therapy. Non-responders received additional vancomycin or all three substances of phase I in phase II. In phase III, all patients with persistent fever were then treated with amphotericin B plus 5-flucytosine and rifampin and randomized for the continuation of the double beta lactam regimen or additional imipenem/cilastatin. 667 (52.9%) of 1260 evaluable patients had FUO during the whole study period, of which 62.5% could be cured in phase I, 43.2% of non-responders in phase II and 55% of persistently febrile patients in phase III. The overall rate of complete response was 79.5%. 2.8% were non-responders, 11.7% were not evaluable for response and 40 patients (6%) died during the study, 24 (60%) of whom due to the underlying disease or the toxicity of antileukemic therapy. A significant difference between the treatment groups could not be detected in either of the three study phases.

Controlled trials of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients

The efficacy and safety of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients were compared with moxalactam plus piperacillin, ceftazidime plus piperacillin, and imipenem alone in two separate clinical trials. All patients also received prophylactic vitamin K. When National Committee for Clinical Laboratory Standards breakpoints for susceptibility were used, a greater proportion of pretherapy isolates of gram-negative aerobic bacilli and gram-positive organisms were found to be susceptible to cefoperazone (94 percent) and imipenem (91 percent) than to moxalactam (84 percent), ceftazidime (85 percent), or piperacillin (85 percent). In trial I, the overall response rates for documented or possible infections were 78 percent (76 of 97 patients) for cefoperazone/piperacillin and 80 percent (72 of 90 patients) for moxalactam/piperacillin. In trial II, the overall response rates were 86 percent (25 of 29 patients) for cefoperazone/piperacillin, 74 percent (20 of 27 patients) for ceftazidime/piperacillin, and 72 percent (21 of 29 patients) for imipenem alone. There was no nephrotoxicity or hemorrhage related to the study drugs. Diarrhea was more frequent with each of the double beta-lactam regimens, whereas nausea and seizures were more common with imipenem given at a dosage of 1.0 g intravenously every six hours. Seizures occurred in three of 29 imipenem-treated patients but in none of 243 patients treated with the double beta-lactam regimens (p <0.001). These results suggest that cefoperazone plus piperacillin provides adequate coverage for most common bacterial pathogens and is safe and effective therapy for febrile granulocytopenic patients.

Cefoperazone plus piperacillin versus mezlocillin plus tobramycin as empiric therapy for febrile episodes in neutropenic patients

The double beta-lactam combination of cefoperazone plus piperacillin was compared with an aminoglycoside-containing regimen of mezlocillin plus tobramycin in a prospective, randomized trial of empiric therapy for febrile neutropenic patients (neutrophils no more than 1,000/mm 3). Thirty febrile episodes were treated with cefoperazone plus piperacillin and mezlocillin plus tobramycin, respectively. There was no significant difference between the two groups with respect to age, sex, pretherapy neutrophil count, and mean duration of therapy. The majority of patients had neutrophil counts of no more than 200/mm 3 at the initiation of therapy. Only microbiologically and clinically documented infections were evaluated for efficacy. The cefoperazone plus piperacillin regimen appeared to have a comparable response rate with the mezlocillin plus tobramycin regimen (20 of 24 patients [83 percent] versus 16 of 23 patients [70 percent]). Gram-positive micro-organisms were seen predominantly in this study, with the cefoperazone plus piperacillin regimen achieving a bacteriologic response in 84 percent, as opposed to 60 percent for those organisms treated with the mezlocillin plus tobramycin regimen. Neither regimen was totally effective against coagulase-negative staphylococci. Eight superinfections occurred in the cefoperazone plus piperacillin arm, whereas 11 superinfections occurred in the mezlocillin plus tobramycin arm. Although fungal superinfections were most common, the number of gram-positive superinfections in the mezlocillin plus tobramycin arm exceeded those seen in the cefoperazone plus piperacillin arm. The incidence of antibiotic-related side effects was similar in the two groups. Hypokalemia was most frequently seen. Both skin rashes and nephrotoxicity were more common with mezlocillin plus tobramycin. Cefoperazone plus piperacillin was found to be effective empiric therapy in febrile neutropenic patients. This double beta-lactam combination may be particularly useful for patients who have or are at high risk for the development of renal insufficiency.

Randomized trial of beta-lactam regimens in febrile neutropenic cancer patients

A three-arm prospective randomized trial was designed to compare the efficacies of piperacillin plus vancomycin, ceftazidime plus vancomycin, or all three drugs as initial therapy for fever in neutropenic cancer patients. The objectives were to determine whether a broad-spectrum penicillin was as effective as a broad-spectrum cephalosporin and whether two beta-lactam antibiotics were more effective than one. Four hundred and seventy of the 519 febrile episodes entered in the study could be evaluated for response. Ceftazidime plus vancomycin was significantly more effective than piperacillin plus vancomycin, considering all febrile episodes (79 percent versus 61 percent, p = 0.001), documented infections (79 percent versus 57 percent, p = 0.004), gram-negative infections (88 percent versus 47 percent, p = 0.001), and bacteremias (81 percent versus 51 percent, p = 0.01). The addition of piperacillin to ceftazidime (piperacillin plus ceftazidime and vancomycin versus ceftazidime plus vancomycin) did not improve the response rate and was associated with a significantly higher incidence of skin rash. Vancomycin plus ceftazidime provides adequate antibiotic coverage for initial treatment of fever in neutropenic patients. This combination was equally effective, less expensive, and less toxic than the double beta-lactam combination used in this study.

14 Infection and Transfusion Therapy in Acute Leukaemia

Granulocytopenia is the single most important risk factor for infection in patients with acute leukaemia. There are limitations to the effective prophylaxis of infection in granulocytopenic patients, but practical measures include the management of the patient in a private hospital room, the requirement of all medical personnel and visitors to wash their hands carefully and to wear masks, restricting the patient to a low-bacteria diet devoid of fresh fruit, vegetables and salads, and the administration of oral antimicrobial agents for gastrointestinal decontamination. When fever develops, empirical therapy with a combination of an aminoglycoside plus an antipseudomonal beta-lactam should be started promptly. A double beta-lactam combination of cefoperazone or ceftazidime plus piperacillin can be substituted if nephrotoxicity is a concern. The addition of empirical intravenous amphotericin may be useful in patients who remain febrile and granulocytopenic on broad-spectrum antibiotics, especially if surveillance cultures indicate fungal colonization. Amphotericin is also the most reliable agent for the treatment of established fungal infections. Acyclovir is not recommended for prophylaxis in acute leukaemia patients but should be reserved for the treatment of well-documented and clinically significant herpes simplex viral infections. During periods of remission, most patients with AML remain free of infection except when they become granulocytopenic again during intensification or consolidation chemotherapy. On the other hand, children with ALL in remission may experience frequent infections unrelated to granulocytopenia as a consequence of their maintenance chemotherapy. Pneumocystis carinii, varicella zoster, and other viruses are common pathogens. Trimethoprim-sulphamethoxazole is effective prophylaxis against Pneumocystis carinii pneumonia in patients with ALL, while intravenous acyclovir is the drug of choice for treatment of varicella zoster infection. Transfusion therapy in the acute leukaemia patient is guided by the patient's peripheral blood counts and degree of sensitization to blood products. Generally, packed red blood cells are given in order to maintain the haematocrit at greater than 30%, while random-donor platelets are administered to keep the platelet count at greater than 20 X 10(9)/l. If refractoriness to platelet transfusions develops, HLA-matched platelets from family members or selected unrelated donors can be used. Similarly, washed or filtered red blood cells may be given to patients with previous and recurrent non-haemolytic febrile reactions to red blood cell transfusions.(ABSTRACT TRUNCATED AT 400 WORDS)

Use of aminoglycosides in immunocompromised patients

For much of the last decade, combination therapy with aminoglycosides has been accepted as the therapeutic approach of choice in immunocompromised hosts. Improved clinical results have also correlated with the presence of synergistic interactions between the aminoglycoside and beta-lactam components of a regimen. Differences between the aminoglycosides and beta-lactam agents remain a subject of controversy. Studies at the University of California, Los Angeles, Medical Center suggest that amikacin interacts more frequently in a synergistic manner with beta-lactams than do alternative aminoglycosides. Amikacin has been used experimentally and (following licensure) without reservation at the University of California, Los Angeles, Medical Center since 1973. Almost 100 blood isolates of both Pseudomonas aeruginosa and Klebsiella pneumoniae collected during the last 12 years have been retested, and no evidence of increased aminoglycoside resistance was found. A relatively new development is interest in empiric therapeutic regimens that employ two beta-lactam agents. In a large, recently completed study, less satisfactory results were observed in P. aeruginosa infections treated with the “double beta-lactam” than in those treated with the regimen containing amikacin; furthermore, nephrotoxicity and eighth nerve damage occurred no more commonly in the group receiving amikacin than in recipients of the double beta-lactam regimen.

Use of discriminative models of Pseudomonas aeruginosa bacteremia in granulocytopenic rats for testing antimicrobial efficacy.

The efficacy of single agent and combination antibiotic therapy was evaluated in rats with severe granulocytopenia and Pseudomonas aeruginosa infection using animal survival, rates of bacteremia and the emergence of resistant organisms as criteria. In this model end points following single agent therapy with imipenem/cilastatin and the synergistic combination of moxalactam plus amikacin were comparable. At a high bacterial challenge dose, equivalent results were obtained using single agent therapy with either piperacillin or ticarcillin. Results were also similar following therapy with piperacillin or ticarcillin in synergistic combination with amikacin. At a lower bacterial challenge dose, aminoglycoside therapy was superior to therapy with the beta-lactams. Therapy with the in vitro synergistic double beta-lactam combination of ceftazidime plus piperacillin was no more effective than therapy with the individual compounds. Results from these studies in this discriminative animal model have in part been used to formulate prospective clinical antibiotic studies in granulocytopenic cancer patients.

Double beta-lactam therapy in the immunocompromised host.

Double beta-lactam therapy in the immunocompromised host.