Viridans Group Streptococci in Pediatric Leukemia and Stem Cell Transplant: Review of a Risk-stratified Guideline for Empiric Vancomycin in Febrile Neutropenia.

Viridans group streptococci (VGS) are an important cause of sepsis in immunosuppressed children. We reviewed the effectiveness of risk-stratified addition of vancomycin to empiric febrile neutropenia therapy among 107 children with leukemia or undergoing an allogeneic transplant. Of 19 VGS bacteremia episodes, 78.9% were susceptible to risk-stratified antibiotics including 100% from high-risk patients. All blood cultures were flagged positive within 24 hours.

Bloodstream infection by multidrug-resistant Streptococcus oralis in a leukemic patient with febrile neutropenia after hematopoietic stem cell transplantation.

We reported the case of a patient with leukemia who developed febrile neutropenia after hematopoietic stem cell transplantation. Blood culture results revealed the presence of Streptococcus oralis, while antimicrobial susceptibility testing showed the resistance to penicillin and cephem. Furthermore, isolates were not susceptible to either meropenem or daptomycin but not to vancomycin. S oralis is known to belong to Streptococcus mitis group and be a causative agent of bacteremia in the neutropenic patients, but multidrug resistance of S oralis is rare. Our findings suggest that we might pay attention to the emergence of the microorganisms acquiring multidrug resistance in neutropenic patients.

Bacterial Spectrum and Antimicrobial Resistance Pattern in Cancer Patients with Febrile Neutropenia

Background: Bacterial bloodstream infections are one of the most common complications in cancer patients under treatment. Bacteremia in these patients is a medical crisis that needs antibiotic treatment. The aim of this study was to determine bacterial spectrum and antimicrobial resistance pattern in febrile neutropenic cancer patients. Methods: In this prospective study, 212 cancer patients with febrile neutropenia who were referred to Shahid Sadoughi hospital in Yazd from 2012 to 2015 were participated. Bacterial pathogens isolated by the BACTEC media and antimicrobial susceptibility tests performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: The mean age of patients was 43.5 ± 24.98 years old. Out of 212 participants, 62.3℅ (132/212) were suffering from hematologic malignancies, and 37.7℅ (80/212) had solid tumors. Gram-negative bacteria were the predominant microorganisms (84.9℅). E.coli was the most frequently isolated pathogen (38.68 %), followed by Klebsiella (14.15℅) and Acinetobacter species (11.32℅). In addition, Staphylococcus epidermidis was the most common isolated Gram-positive bacteria (8.5℅). Gram-negative bacteria were susceptible to ciprofloxacin with a response range of 53.7% to 100%. The majority of E.coli isolates were sensitive to ceftazidime (87.8℅) and were resistance to Co-trimoxazole (15.8℅). Klebsiella isolates were 100% susceptible to cephalosporins, meropenem and imipenem. Conclusion: The majority of bacterial pathogens were resistance to various antibiotics. Judicious use of antibiotic therapy can prevent the emergence and spread of antibiotic-resistant Gram-negative bacteria.

In Vitro Comparison of Ceftolozane-Tazobactam to Traditional Beta-Lactams and Ceftolozane-Tazobactam as an Alternative to Combination Antimicrobial Therapy for Pseudomonas aeruginosa.

Guidelines for the treatment of sepsis, febrile neutropenia, and hospital-acquired pneumonia caused by Pseudomonas aeruginosa include empirical regimens incorporating two antibiotics from different classes with activity against P. aeruginosa for select at-risk patients to increase the likelihood that the organism will be susceptible to at least one agent. The activity against P. aeruginosa and the rates of cross-resistance of ceftolozane-tazobactam were compared to those of the ß-lactam comparators cefepime, ceftazidime, piperacillin-tazobactam, and meropenem alone and cumulatively with ciprofloxacin or tobramycin. Nonurine P. aeruginosa isolates were collected from adult inpatients at 44 geographically diverse U.S. hospitals. MICs were determined using reference broth microdilution methods. Of the 1,257 isolates collected, 29% were from patients in intensive care units and 39% were from respiratory sites. The overall rate of susceptibility to ceftolozane-tazobactam was high at 97%, whereas it was 72 to 76% for cefepime, ceftazidime, piperacillin-tazobactam, and meropenem. The rate of nonsusceptibility to all four comparator ß-lactams was 11%; of the isolates nonsusceptible to the four comparator ß-lactams, 80% remained susceptible to ceftolozane-tazobactam. Among the isolates nonsusceptible to the tested ß-lactam comparators, less than half were susceptible to ciprofloxacin. By comparison, approximately 80% of the ß-lactam-nonsusceptible isolates were susceptible to tobramycin, for overall cumulative susceptibility rates of 94 to 95%, nearly 10% higher than that of the ciprofloxacin-ß-lactam combinations and approaching that of ceftolozane-tazobactam as a single agent. The rates of susceptibility to ceftolozane-tazobactam were consistently high, with little observable cross-resistance. Ceftolozane-tazobactam monotherapy performed at or above the level of commonly utilized combination therapies on the basis of in vitro susceptibilities. Ceftolozane-tazobactam should be considered for use in patients at high risk for resistant P. aeruginosa infection and as an alternative to empirical combination therapy, especially for patients unable to tolerate aminoglycosides.

Low rates of antibiotic resistance and infectious mortality in a cohort of high-risk hematology patients: A single center, retrospective analysis of blood stream infection.

Febrile neutropenia (FN) is a medical emergency and can represent a life-threatening complication for hematology patients treated with intensive chemotherapy regimens. In clinical practice, the diagnostic yield of blood cultures and other investigations which aim to identify a causative organism or site of infection is low. We have retrospectively examined all blood cultures collected in a "real world" cohort of patients receiving chemotherapy for acute leukemia and patients with aggressive lymphoma treated with Hyper-CVAD/MTX-cytarabine, at a single tertiary center over a five-year period. In this cohort, the 30-day mortality following confirmed blood stream infection (BSI) was 5.9%, which is lower than most reports in the recent literature. We compared the blood culture results of inpatients undergoing induction chemotherapy and outpatients presenting with fevers and found a significantly higher rate of proven BSI in the outpatient group. In all settings, gram-negative organisms were most common. The rate of resistance to first-line empiric antibiotics among pathogenic isolates was 11.6% in the whole cohort, independent of blood culture circumstances. There was a trend to higher resistance rates among inpatients undergoing induction chemotherapy compared to patients presenting to the emergency department (17.4% vs 7.5%) but this did not reach statistical significance. We also report low rates of ciprofloxacin resistance (5% of isolates), in a center where universal fluoroquinolone prophylaxis is not employed. Our low resistance and mortality rates support our current therapeutic strategies, however presence of resistant organisms across the spectrum of indications for BC collection highlights the importance of surveilling local patterns, escalating antimicrobial therapy in the deteriorating patient, and considering advanced techniques for the rapid identification of resistance in this patient population.

Ciprofloxacin prophylaxis delays initiation of broad-spectrum antibiotic therapy and reduces the overall use of antimicrobial agents during induction therapy for acute leukaemia: A single-centre study.

BACKGROUND: Due to an outbreak of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, the routine use of fluoroquinolone prophylaxis was questioned. As a result, this study was conducted with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of broad-spectrum antibioctics and anti-mycotics. METHODS: A cohort of 139 consecutive patients with acute leukaemia treated with remission-inducing induction chemotherapy between 2004-2012 at the Department of Haematology in Uppsala University Hospital was analysed. RESULTS: Fifty-three patients (38%) received broad-spectrum antibiotics at the initiation of chemotherapy and were not eligible for prophylaxis. Of the remaining patients, the initiation of broad-spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The median duration of systemic antibiotic treatment was 6 days shorter in patients receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the cumulative (total) median days on systemic antibiotic treatment was shortened by 8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02), carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p < 0.01) were used significantly less often when ciprofloxacin prophylaxis was given. CONCLUSIONS: Ciprofloxacin prophylaxis delayed empiric therapy by 3 days and reduced overall antibiotic use in this study. These benefits must be evaluated vs the risks of development of resistant bacterial strains, making fluoroquinolone prophylaxis an open question for debate.

Antibiotic susceptibility of Gram-negatives isolated from bacteremia in children with cancer. Implications for empirical therapy of febrile neutropenia.

BACKGROUND: Monotherapy is recommended as the first choice for initial empirical therapy of febrile neutropenia, but local epidemiological and antibiotic susceptibility data are now considered pivotal to design a correct management strategy. AIM: To evaluate the proportion of Gram-negative rods isolated in bloodstream infections in children with cancer resistant to antibiotics recommended for this indication. MATERIALS & METHODS: The in vitro susceptibility to ceftazidime, piperacillin-tazobactam, meropenem and amikacin of Gram-negatives isolated in bacteremic episodes in children with cancer followed at the Istituto "Giannina Gaslini", Genoa, Italy in the period of 2001-2013 was retrospectively analyzed using the definitions recommended by EUCAST in 2014. Data were analyzed for any single drug and to the combination of amikacin with each ß-lactam. The combination was considered effective in absence of concomitant resistance to both drugs, and not evaluated by means of in vitro analysis of antibiotic combinations (e.g., checkerboard). RESULTS: A total of 263 strains were evaluated: 27% were resistant to piperacillin-tazobactam, 23% to ceftazidime, 12% to meropenem and 13% to amikacin. Concomitant resistance to ß-lactam and amikacin was detected in 6% of strains for piperacillin-tazobactam, 5% for ceftazidime and 5% for meropenem. During the study period there was a nonsignificant increase in the proportions of strains resistant to ß-lactams indicated for monotherapy, and also increase in the resistance to combined therapies. CONCLUSION: in an era of increasing resistance to antibiotics guideline-recommended monotherapy could be not appropriate for initial empirical therapy of febrile neutropenia. Strict local survey on etiology and antibiotic susceptibility is mandatory for a correct management of this complication in cancer patients.

[Modalities of management of cancer patients with febrile neutropenia in the oncology emergency unit of Gustave-Roussy and their related costs]. / Modalités de prise en charge des neutropénies fébriles chez les patients traités pour une néoplasie solide dans le service d'urgence de cancérologie Gustave-Roussy et leurs impacts économiques.

BACKGROUND: Febrile neutropenia (FN) is a severe chemotherapy side effect. Hospitalization is recommended for FN episode of high-risk (HR) of complications. Management of FN at lower risk of complications remains unclear. METHODS: This is a prospective observation study in patients with solid tumors admitted to the emergency department FN. Collected data included demographics, clinical, biological, therapeutic costs, MASCC score and complications. RESULTS: Hundred and thirty-seven consecutive FN were recorded in 128 patients. Twenty-six FN (19%) were managed at home (all of them had a MASCC score ≥ 21); 111 (81%) were treated at hospital of which 37 NF were at HR of complications based on clinical and biological parameters (all of them had a MASCC score < 21) and for 74 of them the admission could be discussed (MASCC < 20 or ≥ 20). This group of patients was considerate with intermediate risk (IR). All IR patients were treated with the same antibiotics than outpatients, i.e. ceftriaxone in 36 cases (49%) or amoxicillin/clavulanic acid and ciprofloxacin in 38 cases (51%). For these 74 cases, any severe complication was recorded. Antibiotics were adapted for only 12% of these patients according to bacteriology results. CONCLUSION: This study showed the limits of the MASCC score. We did not observe any severe complications in patients admitted to the hospital according to clinical and biological parameters and with the high risk score MASCC. This study had some methodological bias but it allowed us to estimate the cost of the different ways of management and the difficulties to decide the hospitalization in FN.

Pharmacoeconomic evaluation of caspofungin versus liposomal amphotericin B in empirical treatment of invasive fungal infections in Turkey.

Invasive fungal infections (IFIs) are a major concern within healthcare systems. This pharmacoeconomic study evaluated the use of caspofungin (CAS) versus liposomal amphotericin B (L-AmB) in the empirical treatment of IFIs within the Turkish healthcare system. A decision-analytic model was adopted, utilising data from a randomised, non-inferiority clinical trial and a panel of clinical experts in Turkey. A five-point composite outcome measure was used to evaluate both agents. Sensitivity analyses were performed. In the base-case scenario, CAS was preferred over L-AmB by Turkish Lira (TL) 3961 per patient treated, TL 12 904 per successfully treated patient and TL 3972 per death averted. One-way sensitivity analysis did not change the study outcome. Monte Carlo simulation concluded a 71.0% chance of the outcome favouring CAS. The results were most sensitive to changes in length of stay. This is the first economic evaluation of the empirical treatment of IFIs in Turkey and suggests that CAS is more cost effective than L-AmB.