Empirical Monotherapy Research Articles

A Prospective, Open-Label Noncomparative Study with Piperacillin-Tazobactam Monotherapy as Management of Fever in Patients with Acute Leukemia

We evaluated the efficacy of piperacillin-tazobactam monotherapy as empiric therapy of fever in acute leukemia patients in a total of 80 consecutive febrile episodes. The overall success rate was 75% with success without modification in 34% (afebrile at 72 h) and an overall death rate of 10%. No significant differences were seen in correlation between clinical outcome and phases of underlying disease. The success without modification was higher in patients with fever of unknown origin (FUO) than in those with documented infections (47% and 25% respectively). There were no significant differences in correlations between clinical response and degree of neutropenia. Our study suggests that empirical first-line monotherapy with piperacillin-tazobactam may be a reasonable option in patients with acute leukaemia, although in documented infections the response is frequently inadequate.

Cefoperazone-Sulbactam for Treatment of Intra-Abdominal Infections: Results from a Randomized, Parallel Group Study in India

Combinations of a third-generation cephalosporin and metronidazole, with or without an aminoglycoside, often are used for the treatment of intra-abdominal infections in surgical settings. Simpler regimens that preserve an adequate spectrum of coverage, but allow easier administration and have fewer side effects, may be a more desirable option. This randomized, open-label, active comparator study evaluated the effectiveness (non-inferiority hypothesis) of the beta-lactam/beta-lactamase inhibitor combination cefoperazone-sulbactam (2-8 g/day), compared with ceftazidime (2-6 g/day)-amikacin (15 mg/kg/day)-metronidazole (500 mg three times daily) in 154 and 152 subjects, respectively, having intra-abdominal infections. The study was conducted at 17 centers in India. Non-inferiority of cefoperazone-sulbactam (91.9%) compared with ceftazidime-amikacin-metronidazole (81.8%) was demonstrated for continued resolution of clinical signs and symptoms at the 30-day follow-up (primary endpoint) with a treatment difference of 10.1% (95% confidence interval 2.1%, 18.1%; pre-defined non-inferiority limit > -12.5%). Superiority of cefoperazone-sulbactam also was demonstrated for this endpoint, with significantly more subjects achieving continued resolution at the 30-day follow-up than in the comparator group (p = 0.015). On microbiologic outcomes, cefoperazone-sulbactam had higher success rates than ceftazidime-amikacin-metronidazole (92.9% vs. 80.0%). The pathogens (202 isolated) isolated most commonly were Escherichia coli (38.6%) and Klebsiella spp. (12.9%). The incidence of treatment-related adverse events was 6.5% and 16.4% in the cefoperazone-sulbactam and ceftazidime-amikacin-metronidazole groups, respectively, with more discontinuations due to treatment-related adverse events in the comparator arm (3.2% vs. 9.9%). Empirical cefoperazone-sulbactam monotherapy could be a useful adjunct to surgical intervention for intra-abdominal infections.

Ceftobiprole: An Extended-Spectrum Anti–Methicillin-Resistant Staphylococcus aureus Cephalosporin

To summarize and evaluate the literature concerning ceftobiprole. Literature identification was conducted through MEDLINE (1966-February 2008) and International Pharmaceutical Abstracts (1970-February 2008) using the terms ceftobiprole, medocaril, BAL 5788, RO-5788, BAL 9141, RO 63-9141, pyrrolidinone cephalosporin, MRSA, complicated skin and skin-structure infections (cSSSIs), community-acquired pneumonia, and nosocomial pneumonia. Additional publications were identified through a review of articles and abstracts from infectious disease meetings. All articles in English were evaluated and all pertinent information was included. Ceftobiprole medocaril is an extended-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus spp., vancomycin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant Enterococcus faecalis, Enterobacteriaceae, and Pseudomonas aeruginosa. Inactivity includes extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and Enterococcus faecium. Preliminary data suggest that ceftobiprole may be effective with a 1-hour infusion of 500 mg every 12 hours for gram-positive infections and 500 mg every 8 hours with a 2-hour infusion for polymicrobial infections. Two clinical trials support these dosing regimens for cSSSIs. Ceftobiprole was noninferior to vancomycin in suspected gram-positive cSSSIs, with cure rates of 93.3% and 93.5%, respectively. Furthermore, ceftobiprole was noninferior to vancomycin and ceftazidime in polymicrobial cSSSIs (cure rates 90.5% vs 90.2%, respectively). Although the total number of adverse effects was similar to those of the comparator, more patients in the ceftobiprole group experienced nausea, vomiting, and dysgeusia. The activity of ceftobiprole and limited clinical data suggest that it may be useful as empiric monotherapy for cSSSI and in combination with other antimicrobials in lower respiratory tract infections for which Phase 3 clinical trials are currently exploring. Although not shown in vitro, ceftobiprole may induce resistance due to its broad spectrum of activity. Approval is expected for the treatment of cSSSI.

Febrile urinary tract infection in children: ampicillin and trimethoprim insufficient as empirical mono-therapy

The aim of this study was to characterize the pathogens and their antibiotic susceptibilities in defined groups of children (total number 694) with urinary tract infection (UTI) regarding age, first UTI (FUTI) or recurrent UTI (RUTI), renal abnormalities or vesico-ureteric reflux (VUR) in order to optimize empirical antibiotic therapy and prophylaxis. In patients aged between 1 month and 24 months with a first febrile UTI (FUTI; n = 205) the leading pathogen was Escherichia coli (E. coli) (83.4%). In comparison with patients with FUTI, those with RUTI (n = 24) had more Enterococcus and Enterobacter infections and higher resistance rates of E. coli against trimethoprim (TMP), trimethoprim/sulfamethoxazole (SXT) or ampicillin (AMP). Boys with ultrasound-detected renal abnormalities (n = 71) showed 14.2% Pseudomonas and 59.1% E. coli infections versus girls (n = 48) (2.1% Pseudomonas and 93.7% E. coli). Of 390 patients who underwent voiding cysto-urethrography, 31.5% had VUR. Of them, 45.5% received antimicrobial prophylaxis with SXT (n = 30) or cefazolin (n = 26). There was no difference between girls (n = 242) and boys (n = 148) regarding the frequency of VUR and pathogens. There were more TMP- and SXT-resistant E. coli cultures from patients with VUR (37.8%) than from those without VUR (25.8%). Treatment with TMP, SXT and AMP alone appeared to be insufficient in many cases because of high resistance rates of E. coli and other uropathogens.

Gram-negative organisms predominate in Hickman line-related infections in non-neutropenic patients with hematological malignancies

Catheter-related blood stream infections (CRBSI) cause significant morbidity and mortality in patients with hematological malignancies. Previous studies have identified a predominance of gram-positive organisms causing CRBSI but they included both neutropenic and non-neutropenic patients with solid organ and hematological malignancies. The aim of our study was to evaluate the incidence and microbiological profile of CRBSIs in a specific cohort of patients with hematological malignancies in their non-neutropenic phase of illness. A detailed retrospective review was done from January 2003 to December 2005 on all patients with hematological malignancies who had double-lumen non-antibiotic impregnated tunneled CVCs (Hickman catheters) inserted in our hospital to identify those fulfilling our criteria for CRBSI episodes. Amongst 273 evaluable patients, 61 developed CRBSI on 70 occasions. In contrast to previous studies, there was a predominance of gram-negative infections (68%). The majority (73%) of initial CRBSI episodes required catheter removal within 7 days of onset. Vancomycin and cefepime was the most common initial antibiotic regimen used. This study highlights the predominance of gram-negative infections in our cohort of non-neutropenic patients with underlying hematological malignancies who had Hickman catheters whose lines were not salvageable in the majority of cases. Empiric monotherapy with an antimicrobial agent with broad spectrum gram-negative cover needs to be given upfront pending results of the nature and sensitivity of organisms identified.

Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia

Streptococcus pneumoniae has been consistently shown to represent the most frequent causative agent of community-acquired pneumonia (CAP) and pneumococcal antibiotic resistance towards different families of antibiotics continues to be a much-debated issue. Microbial resistance causes a great deal of confusion in choosing an empirical treatment for pneumonia and this makes it necessary to know which factors actually determine the real impact of antimicrobial resistance on the outcome of pneumococcal infections. Several different aspects have to be taken into account when analyzing this matter, such as the study design, the condition of the patient at the time of diagnosis, the choice of the initial antimicrobial regimen (combination or monotherapy) and the pharmacokinetic/pharmacodynamic variables of the chosen antibiotic. It is generally accepted that in the treatment of β-lactam-resistant pneumococcal infections, the use of standard antipneumococcal β-lactam agents is unlikely to impact negatively on the outcome of CAP when appropriate agents are given in sufficient doses. As a general rule, for infections with penicillin-sensitive strains, penicillin or an aminopenicillin in a standard dosage will be effective; in the cases of strains with intermediate resistance, β-lactam agents are still considered appropriate treatment although higher dosages are recommended; finally, infections with isolates of high-level penicillin resistance should be treated with alternative agents such as the third-generation cephalosporins or the new antipneumococcal fluoroquinolones. In areas of high prevalence of high-level macrolide resistance, empirical monotherapy with a macrolide is not optimal for the treatment of hospitalised patients with moderate or moderately-severe CAP. Fluoroquinolones are considered to be excellent antibiotics in the treatment of pneumococcal CAP in adults, but their general recommendation has been withheld due to fears of a widespread development of resistance. Most international guidelines recommend combination therapy (β-lactam plus a macrolide) for the treatment of hospitalised patients with CAP.

Panipenem Versus Cefepime as Empirical Monotherapy in Adult Cancer Patients with Febrile Neutropenia: A Prospective Randomized Trial

To compare the efficacy and safety of panipenem/betamipron with cefepime as empirical monotherapy for adult cancer patients with febrile neutropenia, a randomized, open-label, comparative trial was performed. All enrolled patients were randomly assigned to receive either panipenem or cefepime. All febrile episodes were classified as microbiologically defined infection (MDI), clinically defined infection (CDI) or unexplained fever (UF). Clinical responses to antibiotic therapy were defined as success, initial response but regimen modified or failure. A total of 116 patients were enrolled: 55 patients in the panipenem group and 61 patients in the cefepime group. Demographic and clinical characteristics were similar in the two groups (P > 0.05). In the final evaluation, the success rate for the panipenem group (89.1%) was similar to that of the cefepime group (91.8%) (non-inferiority, P = 0.002, 95% confidence interval: -13.48%, 10.35%). Of the 18 bacterial isolates, nine (50%) were gram-positive and nine (50%) were gram-negative. The prevalence of adverse events in the panipenem group (23.6%) were similar to those in the cefepime group (23.0%) (P = 0.93). All of the adverse events were well tolerated and transient. Although larger studies are necessary, panipenem appeared to be as effective and safe as cefepime for empirical monotherapy in the treatment of adult cancer patients with febrile neutropenia.

Antibiotic selection is crucial for optimal empiric monotherapy of ventilator-associated pneumonia*

Antibiotic selection is crucial for optimal empiric monotherapy of ventilator-associated pneumonia*

Predictors of mortality in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia: the role of empiric antibiotic therapy

The objective of this study was to evaluate prognostic factors and the influence of different empiric antibiotic therapies on outcome and mortality in a cohort of 100 inpatients with bacteraemia (84 cases nosocomial) caused by methicillin-resistant Staphylococcus aureus (MRSA). Patients were investigated by means of a standard protocol at a 944-bed hospital in the years 2000-2004. Empiric antibiotic therapies included vancomycin (n = 49), teicoplanin (n = 20), linezolid (n = 17), other antibiotics active in vitro (n = 7), and inactive antibiotics (n = 7). Overall mortality was 40% (12% among linezolid-treated patients; 46.3% among glycopeptide-treated patients). In bivariate analyses, the following factors were statistically associated with higher mortality: rapidly fatal underlying disease, altered mental status, metabolic acidosis, and acute severe clinical condition at the onset of bacteraemia; development of complications (septic shock, renal failure, and disseminated intravascular coagulopathy); empiric monotherapy with glycopeptides (vs combination therapy with an aminoglycoside); and inadequate empiric treatment. Empiric therapy with linezolid was associated with lower mortality. In multivariate analysis, risk factors associated with higher mortality included acute severity of illness (OR 7.49; 95%CI 1.19-25.3) and altered mental status (OR 4.83; 95%CI 1.22-19.15) at onset, complications (OR 3.42; 95%CI 1.02-17.46), and inappropriate empiric treatment (OR 7.6; 95%CI 1.87-31.14). In multivariate analysis limited to patients who received empiric therapy with either linezolid (n = 17) or glycopeptides (n = 69), linezolid was associated with greater rates of survival (OR 7.7; 95%CI 1.1-53) and microbiological eradication (OR 11.76; 95%CI 1.46-90.9) but not with fewer complications (OR 0.71; 95%CI 0.16-3.25). In conclusion, the main prognostic factors associated with mortality in patients with MRSA bacteraemia are complications, acute severe clinical condition at onset, and inappropriate empiric treatment. Empiric therapy with linezolid was associated with greater survival and more successful microbiological eradication but did not reduce complications.

Diagnosis of Ventilator-Associated Pneumonia

In this issue of the Journal, Heyland et al., writing for the Canadian Critical Care Trials Group, report the results of a multicenter, randomized trial comparing the use of bronchoalveolar lavage and endotracheal aspiration for the diagnosis of ventilator-associated pneumonia.1 This study was part of a larger 2-by-2 factorial design also comparing empirical antimicrobial monotherapy (a carbapenem) and combination therapy (a carbapenem plus a fluoroquinolone). The authors conclude that bronchoalveolar lavage and endotracheal aspiration are associated with similar clinical outcomes and similar overall use of antibiotics. However, several important limitations of the study must be appreciated in order to place . . .

Prospective Randomized Trial of Cefoperazone-Sulbactam Versus Ceftazidime Plus Amikacin and Metronidazole in the Treatment of Intra-Abdominal Infections

Purpose: Monotherapy appears to be a desirable option for treatment of intra-abdominal infections due to the simplicity of its administration, fewer side effects and wide spectrum. This prospective, randomised, open-label, parallel group, phase IV multi-centric study evaluated the efficacy and safety of cefoperazone-sulbactam compared with ceftazidime plus amikacin and metronidazole in the treatment of intra-abdominal infections in Indian patients. Methods: Subjects received study medication [cefoperazone-sulbactam (2–8 g/day) or ceftazidime (2–6 g/day) plus amikacin (15mg/kg/day) plus metronidazole (500 mg tds)] intravenously for 5–14 days. Three hundred and six subjects were clinically evaluable (cefoperazone-sulbactam, n = 154; ceftazidime/amikacin/metronidazole, n = 152). Results: Significantly more patients in the cefoperazone-sulbactam group had continued resolution of their clinical signs and symptoms at the 30-day follow-up visit (92% versus 82%; p= 0.017). The difference between treatments was 10% (95% confidence interval 2.1–18.1), which was higher than the pre-defined non-inferiority limit of >–12.5. The findings were similar even for microbiological outcomes (success or presumed success: cefoperazone-sulbactam, 93%; ceftazidime/amikacin/metronidazole, 80%) at the end of treatment. The incidence of treatment related adverse events was 6% with cefoperazone-sulbactam, vs. 16% with ceftazidime/amikacin/metronidazole. There were more discontinuations in the ceftazidime/amikacin/metronidazole group (10% vs 3%). Conclusions: Empirical cefoperazone-sulbactam monotherapy is a useful alternative to the current standard combination treatment for serious intra-abdominal infections.

Prospective Study of Empiric Monotherapy with Ceftazidime for Low-Risk Grade IV Febrile Neutropenia after Cytotoxic Chemotherapy in Cancer Patients

Purpose: It was the aim of this study to evaluate the results of a prospective study in a single medical center using ceftazidime monotherapy in cancer patients with chemotherapy-induced grade IV febrile neutropenia and a low risk for gram-negative bacteremia. Subjects and Methods: Thirty-eight patients were admitted with low-risk grade IV febrile neutropenia after chemotherapy for solid tumors. The median patient age was 57 years (range 18–74). Sixteen patients (42%) developed febrile neutropenia after the first cycle of current chemotherapy line, 9 patients (24%) received 2–3 cycles and 13 patients (34%) received more than 3 chemotherapy cycles before manifesting febrile neutropenia. Five patients were treated with prophylactic granulocyte colony-stimulating factor commenced 24 h after completion of the chemotherapy cycle. Empiric monotherapy with intravenous ceftazidime was started on admission and administered 2 g every 8 h. Results: The mean polymorphic nuclear cell count on admission was 231 cells/mm³. Ceftazidime therapy was well tolerated. Twenty-five (66%) patients responded with clinical improvement and complete resolution of fever within 48 h after initiation of ceftazidime therapy. Thirty-two (84%) patients were afebrile after 72 h of therapy. Thirty-three patients (87%) remained on unmodified ceftazidime therapy throughout their hospitalization. Five patients (13%) subsequently required modification of the treatment regimen for various reasons. Mean duration of fever and neutropenia were 2 (1–10) days and 4 (1–11) days, respectively. None of the patients discontinued therapy because of adverse effects. No positive blood cultures were obtained. No events of septic shock were observed. Mean duration of hospitalization was 6 days (range 3–12). Conclusion: In our series, monotherapy with intravenous ceftazidime appears safe and effective in cancer patients with low-risk grade IV febrile neutropenia after cytotoxic chemotherapy and may appreciably reduce antibiotics costs.

Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials: authors' response

Sir, Drs Rolston and Bodey have raised several points regarding our study, which we would like to address. We compared broad-spectrum b-lactams currently recommended as first-line empirical monotherapy for febrile neutropenia in the latest Infectious Diseases Society of America (IDSA) guidelines, which include ceftazidime, cefepime, imipenem and meropenem. Indeed, our terminology (i.e. monotherapy) was inaccurate since we included studies that assessed combination therapy when vancomycin was added to both study arms. However, only 4 of the 33 included studies added vancomycin to all patients and 2 studies permitted the addition of vancomycin equally to both study arms when indicated. Exclusion of these studies does not change our results. Specifically, all-cause mortality with cefepime alone is significantly higher than the mortality with ceftazidime monotherapy (cefepime versus ceftazidime RR 1.74, 95% CI 1.02–2.98, 6 studies, values >1 favour ceftazidime). Mortality is similar with ceftazidime and carbapenem monotherapy (ceftazidime versus carbapenems RR 1.10, 95% CI 0.65–1.86, 8 studies). All-cause mortality with cefepime monotherapy remains significantly higher when compared with other monotherapies combined (cefepime versus others RR 1.52, 95% CI 1.07–2.14, 14 studies). Clinical failure results are identical to those presented in our publication. Our original objective was to guide clinicians in the selection of the type of the b-lactam used for monotherapy, or in combination with vancomycin when indicated. Local resistance patterns should be used to guide treatment. Obviously, antibiotics that are not active given local epidemiology should not be used. The (external) validity of any study to the local settings must be considered before applying its conclusions. Drs Rolston and Bodey focus the interpretation of our results in light of the epidemiology at their centre. However ceftazidime may be used for monotherapy in locations where antibiotic resistance patterns permit its use. Drs Rolston and Bodey quote the results of a meta-analysis comparing b-lactam monotherapies, showing ‘clear and statistically significant inferiority of ceftazidime’. This is not a systematic review, but a preliminary analysis of 25 randomized controlled trials ‘available in electronic databases’. This metaanalysis combined trials assessing b-lactam monotherapy and b-lactam-aminoglycoside combination therapy. The outcome reported by Glasmacher et al. is ‘response to the initial empirical antibiotic treatment without modification’ (opposite of treatment failure as defined in our study). Treatment failure in these trials is a composite endpoint driven mainly by modifications of the empirical treatment. Most of these trials were not blinded and treatment modifications were more common with ceftazidime when compared with a newer antibiotic. Comparability of study results is highly dependent on the definitions used in the study. The primary outcome on which our conclusions are based is all-cause mortality. This is also the main outcome for the patient. Other outcomes meaningful to patients include time to clinical response, need for invasive procedures, duration of hospital stay, but not treatment modification. Our study shows that cefepime was associated with significant higher all-cause mortality than comparators, despite its advantages in vitro. We cannot continue treating patients with an antibiotic that results in higher mortality unless the data, or our interpretation, are rebutted in a convincing way. Should evidence be discarded because epidemiology has changed? Randomized controlled trials have paved the path to evidence-based treatment of febrile neutropenia. Current treatment is based on the earliest trials conducted by Dr Bodey and colleagues. Clinicians debating the type of monotherapy most appropriate for their locale should look at the evidence available. Appropriately conducted meta-analyses originating from systematic reviews enable unbiased integration of the evidence and assessment of patients’ safety. We believe that systematic reviews are a powerful tool to examine the evidence. The evidence should then be examined in the light of local patterns of pathogens and resistance at each medical centre. The applicability of results to specific settings should indeed be carefully considered.

Comment on: Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials

Comment on: Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials

Update on management of infections in cancer and stem cell transplant patients

Infections are the most important causes of morbidity and mortality in patients with aggressive malignancies and those undergoing allogeneic stem cell transplantation. The introduction of new therapeutic approaches including the use of nucleoside analogs and of monoclonal antibodies to CD20 and CD52 and the increased use of matched unrelated stem cell donors has resulted in new challenges with regard to systemic viral and fungal infections. In patients with bacterial infections, emergence of resistance to formerly widely used antibiotics as well as a shift of causative pathogens towards a predominance of multi-resistant gram-positive cocci has to be taken into consideration. In high-risk neutropenic patients with fever of unknown origin, prompt empiric monotherapy with piperacillin-tazobactam, cefepime, ceftazidime, or a carbapenem is mandatory. In patients with lung infiltrates, early preemptive intervention with an antifungal active against aspergilli is recommended, whereas in patients with catheter-related, skin or soft tissue infections, preemptive addition of a glycopeptide shows a high response rate. The prompt preemptive use of ganciclovir or foscarnet in allogeneic stem cell transplant recipients can reliably be guided by serial monitoring of cytomegalovirus antigen and polymerase chain reaction monitoring.

Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials

Early, empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia. Several beta-lactams are accepted for monotherapy. We asked whether patients' outcomes are influenced by the chosen beta-lactam. Systematic review and meta-analysis of randomized controlled trials comparing anti-pseudomonal beta-lactams administered as empirical monotherapy for febrile neutropenia, with or without vancomycin. The search included The Cochrane Library, PubMed, Embase, Lilacs databases, bibliography, conference proceedings, trial registries and FDA new drug approvals. Two reviewers independently applied selection criteria, performed quality assessment and extracted the data. Trials assessing the same beta-lactam were pooled using the fixed effect model. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. The primary outcome assessed was all-cause mortality. Thirty-three trials fulfilled inclusion criteria. Cefepime was associated with higher all-cause mortality at 30 days than other beta-lactams (RR 1.44, 95% CI 1.06-1.94, 3123 participants). Carbapenems were associated with fewer treatment modifications, including addition of glycopeptides, than ceftazidime or other comparators. Adverse events were significantly more frequent with carbapenems, specifically pseudomembranous colitis (RR 1.94, 95% CI 1.24-3.04, 2025 participants). All-cause mortality was unaltered. Piperacillin/tazobactam was compared only with cefepime and carbapenems, in six trials. No significant differences were demonstrated with paucity of data for all-cause mortality. The use of cefepime for febrile neutropenia is associated with increased mortality and should be carefully considered pending further analysis. Empirical use of carbapenems entails fewer treatment modifications, but an increased rate of pseudomembranous colitis. Ceftazidime, piperacillin/tazobactam, imipenem/cilastatin and meropenem appear to be suitable agents for monotherapy.

Empirical antimicrobial monotherapy in patients after high‐dose chemotherapy and autologous stem cell transplantation: a randomised, multicentre trial

We report on 232 patients undergoing autologous haematopoietic stem cell transplantation (ASCT) entered into a multicentre, randomised trial comparing the efficacy and tolerability of meropenem (MPM) with that of piperacillin/tazobactam (P/T) as empirical antimicrobial first-line therapy for febrile neutropenia. In 27.6% of patients in the MPM group and 22.4% in the P/T group, therapy was initially supplemented with a glycopeptide for venous catheter infection or bacteraemia because of coagulase-negative staphylococci. Complete response rate after 72 h was 63.8% in the MPM group and 49.6% in the P/T group (P = 0.034). Overall complete response rate after treatment modification was 94.0% in the MPM group and 93.1% in the P/T group. Median time to defervescence was 2 d in the MPM group and 3 d in the P/T group. The most frequently isolated pathogens were Gram-positive cocci. Treatment was well tolerated in both groups. One patient (0.4%) died from infection. Empirical first-line therapy with MPM as well as with P/T is safe and effective in febrile episodes emerging after ASCT. Higher response rates to primary treatment can be achieved with MPM.

Antibiotic Resistance Pattern Among Aerobic Gram Negative Bacilli Isolated from Patients in Intensive Care Units

To study the antimicrobial resistance pattern of aerobic Gram-negative bacilli isolated from patients in intensive care units in Hamad Medical Corporation, 108 non-duplicate isolates from 60 patients with nosocomial infections were determined by Vitek machine. The minimal inhibitory concentration of 14 antimicrobials was determined by E-test and results were interpreted according to the National Committee for Clinical Laboratory Standards guidelines. The most common species was Pseudomonas aeruginosa High levels of resistance were seen to second and third generation cephalosporins, piperacillin, fi-lactam Ji-lactamase inhibitors combinations, and gentamicin. The most active agents were amikacin, meropenem and imipenem (resistance 19%, 19%, 20% respectively). We conclude that second and third generation cephalosporins, piperacillin, fi-lactam/fi-lactamase inhibitors combinations and gentamicin are not suitable drugs for empirical monotherapy for aerobic Gram-negative infections in intensive care units in Qatar.

Piperacillin-tazobactam versus cefepime monotherapy for pediatric febrile neutropenia

8550 Background: Febrile neutropenia is a major acute side effect of therapy in pediatric cancer, necessitating prompt initiation of empirical broad-spectrum antibiotics. Methods: Since 1994, monotherapy has been used for empiric initial treatment in our center. Cefepime (C), a fourth generation cephalosporin, was found as effective and safe as ceftazidime in a previous randomized trial in our center (Kebudi R et al, Med Pediatr Oncol 36:434–441,2001). Piperacillin-tazobactam (PT) is an extended spectrum penicillin combined with a beta-lactam inhibitor tazobactam. The aim of this single institution, prospective randomized study is to compare the efficacy of PT and C as empiric monotherapy of febrile neutropenic children with cancer. 40 episodes of fever and neutropenia were randomized to recieve treatment with either PT or C. Patients were analyzed for absolute neutrophil count (ANC) at entry, days with fever, neutropenia, hospitalization and side effects of drugs. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia, failure was death due to infection. Results: In our study group, with a median age of 13 (2–14)years, PT was administered in 20 episodes [16 patients],and C in 20 episodes [15 patients]. There was no statistical difference in the median ANC at entry (28 vs 62/mm3),days with fever (2 vs 2), days with neutropenia (7 vs 6.5), days with antibiotics (7.5 vs 9.5) and days in hospitalization (7.5 vs 9.5) in the PT and C group respectively. An infection was documented microbiologically in 4(%20) vs in 5(%25) episodes and clinically in 9 (%45) vs in 10 (%50) episodes in the PT vs C arm. Episodes with severe neutropenia (% with ANC<100/mm3) was 70 vs 75% ; episodes with ≥7 days of neutropenia were 60 vs 50% in the PT vs C arm. The success rate with initial therapy was 65 vs 60% and the modification was 35 and 40% in the PT vs C arm. Modifications included aminoglicosides in 30 vs 25%, glycopeptides in 15 vs 25%, antifungals in 10 vs 10% in the PT vs C arm. There were no deaths. No major adverse effects were observed in either group. Conclusions: Piperacilin-tazobactam seems to be as effective and safe as cefepime for the empirical treatment of febrile episodes in neutropenic children with cancer. No significant financial relationships to disclose.

Pseudomonas aeruginosa bloodstream infection: importance of appropriate initial antimicrobial treatment.

Pseudomonas aeruginosa bloodstream infection is a serious infection with significant patient mortality and health-care costs. Nevertheless, the relationship between initial appropriate antimicrobial treatment and clinical outcomes is not well established. This study was a retrospective cohort analysis employing automated patient medical records and the pharmacy database at Barnes-Jewish Hospital. Three hundred five patients with P. aeruginosa bloodstream infection were identified over a 6-year period (January 1997 through December 2002). Sixty-four (21.0%) patients died during hospitalization. Hospital mortality was statistically greater for patients receiving inappropriate initial antimicrobial treatment (n = 75) compared to appropriate initial treatment (n = 230) (30.7% versus 17.8%; P = 0.018). Multiple logistic regression analysis identified inappropriate initial antimicrobial treatment (adjusted odds ratio [AOR], 2.04; 95% confidence interval [CI], 1.42 to 2.92; P = 0.048), respiratory failure (AOR, 5.18; 95% CI, 3.30 to 8.13; P < 0.001), and circulatory shock (AOR, 4.00; 95% CI, 2.71 to 5.91; P < 0.001) as independent determinants of hospital mortality. Appropriate initial antimicrobial treatment was administered statistically more often among patients receiving empirical combination antimicrobial treatment for gram-negative bacteria compared to empirical monotherapy (79.4% versus 65.5%; P = 0.011). Inappropriate initial empirical antimicrobial treatment is associated with greater hospital mortality among patients with P. aeruginosa bloodstream infection. Inappropriate antimicrobial treatment of P. aeruginosa bloodstream infections may be minimized by increased use of combination antimicrobial treatment until susceptibility results become known.