Evaluating Initial Empiric Therapy for Neutropenic Fever in Vancomycin-Resistant Enterococcus-Colonized Patients.

OBJECTIVES: Vancomycin-resistant enterococcus infections impact mortality in oncology patients. Given the low rate of vancomycin-resistant enterococcus bacteremia, low virulence of vancomycin-resistant enterococcus, and advent of rapid diagnostic systems, vancomycin-resistant enterococcus-directed empiric therapy in vancomycin-resistant enterococcus-colonized patients with neutropenic fever may be unnecessary, promoting increased antimicrobial resistance, drug-related toxicity, and cost. METHODS: Vancomycin-resistant enterococcus-colonized adults admitted for hematopoietic stem cell transplantation or induction therapy for acute leukemia/myeloid sarcoma with neutropenic fever were stratified by vancomycin-resistant enterococcus bacteremia development and empiric vancomycin-resistant enterococcus-directed antimicrobial strategy for first neutropenic fever (Empiric Therapy vs. non-Empiric Therapy). Primary endpoints included vancomycin-resistant enterococcus-related, in-hospital, and 100-day mortality rates. Secondary outcomes included vancomycin-resistant enterococcus bacteremia incidence for first neutropenic fever and the entire hospitalization, length of stay, Clostridioides difficile infection rate, and duration and cost of vancomycin-resistant enterococcus-directed therapy. RESULTS: During first neutropenic fever, 3 of 70 eligible patients (4%) developed vancomycin-resistant enterococcus bacteremia. Although all 3 (100%) were non-Empiric Therapy, no mortality (0%) occurred. Of 67 patients not developing vancomycin-resistant enterococcus bacteremia, 42 (63%) received Empiric Therapy and 25 (37%) non-Empiric Therapy. Empiric Therapy had significantly greater median duration (3 days vs. 0 days; P<.001) and cost ($1604 vs. $0; P<.001) of vancomycin-resistant enterococcus-directed therapy but demonstrated no significant differences in clinical outcomes. CONCLUSION: Available data suggest Empiric Therapy may offer no clinical benefit to this population, regardless of whether vancomycin-resistant enterococcus is identified in blood culture or no pathogen is found. Such an approach may only expose the majority of patients to unnecessary vancomycin-resistant enterococcus-directed therapy and drug-related toxicities while increasing institutional drug and monitoring costs. Even in the few patients developing vancomycin-resistant enterococcus bacteremia, waiting until the organism is identified in culture to start directed therapy likely makes no difference in mortality. This lack of benefit warrants consideration to potentially omit empiric vancomycin-resistant enterococcus-directed therapy in first neutropenic fever in many of these patients.

Reconsidering Strategies for Managing Chronic Periprosthetic Joint Infection in Total Knee Arthroplasty: Using Decision Analytics to Find the Optimal Strategy Between One-Stage and Two-Stage Total Knee Revision.

BACKGROUND: Periprosthetic joint infection (PJI) following total knee arthroplasty is a growing concern, as the demand for total knee arthroplasty (TKA) expands annually. Although 2-stage revision is considered the gold standard in management, there is substantial morbidity and mortality associated with this strategy. One-stage revision is associated with lower mortality rates and better quality of life, and there has been increased interest in utilizing the 1-stage strategy. However, surgeons are faced with a difficult decision regarding which strategy to use to treat these infections, considering uncertainty with respect to eradication of infection, quality of life, and societal costs with each strategy. The purpose of the current study was to use decision analysis to determine the optimal decision for the management of PJI following TKA. METHODS: An expected-value decision tree was constructed to estimate the quality-adjusted life-years (QALYs) and costs associated with 1-stage and 2-stage revision. Two decision trees were created: Decision Tree 1 was constructed for all pathogens, and Decision Tree 2 was constructed solely for difficult-to-treat infections, including methicillin-resistant infections. Values for parameters in the decision model, such as mortality rate, reinfection rate, and need for additional surgeries, were derived from the literature. Medical costs were derived from Medicare data. Sensitivity analysis determined which parameters in the decision model had the most influence on the optimal strategy. RESULTS: In both decision trees, the 1-stage strategy produced greater health utility while also being more cost-effective. In the Monte Carlo simulation for Decision Trees 1 and 2, 1-stage was the dominant strategy in about 85% and 69% of the trials, respectively. Sensitivity analysis showed that the reinfection and 1-year mortality rates were the most sensitive parameters influencing the optimal decision. CONCLUSIONS: Despite 2-stage revision being considered the current gold standard for infection eradication in patients with PJI following TKA, the optimal decision that produced the highest quality of life was 1-stage revision. These results should be considered in shared decision-making with patients who experience PJI following TKA. LEVEL OF EVIDENCE: Economic and Decision Analysis Level IV. See Instructions for Authors for a complete description of levels of evidence.

Excess cost and inpatient stay of treating deep spinal surgical site infections.

AIM: To determine the excess cost and hospitalisation associated with surgical site infections (SSI) following spinal operations in a New Zealand setting. METHODS: We identified inpatients treated for deep SSI following primary or revision spinal surgery at a regional tertiary spinal centre between 2009 and 2016. Excess cost and excess length of stay (LOS) were calculated via a clinical costing system using procedure-matched controls. RESULTS: Twenty-eight patients were identified. Twenty-five had metalware following spinal fusion surgery, while three had non-instrumented decompression and/or discectomy. Five were diagnosed during their index hospitalisation and 23 (82%) were re-admitted. The average excess SSI cost was NZ$51,434 (range $1,398-$262,206.16) and LOS 37.1 days (range 7-275 days). Infections following metalware procedures had a greater excess cost (average $56,258.90 vs. $11,228.61) and LOS (average 40.4 days vs. 9.7 days) than procedures without metalware. CONCLUSION: The costs associated with spinal SSI are significant and comparable to a previous New Zealand study of hip and knee prosthesis SSI. More awareness of the high costs involved should encourage research and implementation of infection prevention strategies.

Vancomycin-Resistant Enterococcus Colonization and Bacteremia and Hematopoietic Stem Cell Transplantation Outcomes.

The association between pre-hematopoietic stem cell transplantation (HSCT) vancomycin-resistant Enterococcus (VRE) colonization, HSCT-associated VRE bacteremia, and HSCT mortality is disputed. We studied 161 consecutive patients with acute leukemia who underwent HSCT at our hospital between 2006 and 2014, of whom 109 also received leukemia induction/consolidation on our unit. All inpatients had weekly VRE stool surveillance. Pre-HSCT colonization was not associated with increases in HSCT mortality but did identify a subgroup of HSCT recipients with a higher risk for VRE bacteremia and possibly bacteremia from other organisms. The major risk factor for pre-HSCT colonization was the number of hospital inpatient days between initial admission for leukemia and HSCT. One-third of evaluable patients colonized before HSCT were VRE-culture negative on admission for HSCT; these patients had an increased risk for subsequent VRE stool surveillance positivity but not VRE bacteremia. Molecular typing of VRE isolates obtained before and after HSCT showed that VRE strains frequently change. Postengraftment VRE bacteremia was associated with a much higher mortality than pre-engraftment VRE bacteremia. Pre-engraftment bacteremia from any organism was associated with an alternative donor and resulted in an increase in hospital length of stay and cost. Mortality was similar for pre-engraftment VRE bacteremia and pre-engraftment bacteremia due to other organisms, but mortality associated with post-engraftment VRE bacteremia was higher and largely explained by associated severe graft-versus-host disease and relapsed leukemia. These data emphasize the importance of distinguishing between VRE colonization before HSCT and at HSCT, between pre-engraftment and postengraftment VRE bacteremia, and between VRE bacteremia and bacteremia from other organisms.

Frequency, risk factors, and outcomes of vancomycin-resistant Enterococcus colonization and infection in patients with newly diagnosed acute leukemia: different patterns in patients with acute myelogenous and acute lymphoblastic leukemia.

OBJECTIVE To determine the frequency, risk factors, and outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in patients with newly diagnosed acute leukemia. DESIGN Retrospective clinical study with VRE molecular strain typing. SETTING A regional referral center for acute leukemia. PATIENTS Two hundred fourteen consecutive patients with newly diagnosed acute leukemia between 2006 and 2012. METHODS All patients had a culture of first stool and weekly surveillance for VRE. Clinical data were abstracted from the Intermountain Healthcare electronic data warehouse. VRE molecular typing was performed utilizing the semi-automated DiversiLab System. RESULTS The rate of VRE colonization was directly proportional to length of stay and was higher in patients with acute lymphoblastic leukemia. Risk factors associated with colonization include administration of corticosteroids (P=0.004) and carbapenems (P=0.009). Neither a colonized prior room occupant nor an increased unit colonization pressure affected colonization risk. Colonized patients with acute myelogenous leukemia had an increased risk of VRE bloodstream infection (BSI, P=0.002). Other risk factors for VRE BSI include severe neutropenia (P=0.04) and diarrhea (P=0.008). Fifty-eight percent of BSI isolates were identical or related by molecular typing. Eighty-nine percent of bloodstream isolates were identical or related to stool isolates identified by surveillance cultures. VRE BSI was associated with increased costs (P=0.0003) and possibly mortality. CONCLUSIONS VRE colonization has important consequences for patients with acute myelogenous leukemia undergoing induction therapy. For febrile neutropenic patients with acute myelogenous leukemia, use of empirical antibiotic regimens that avoid carbapenems and include VRE coverage may be helpful in decreasing the risks associated with VRE BSI.

[Bacteraemia at a second level hospital: epidemiological study, analysis of pronostic factors associated to mortality and economic cost estimation]. / Bacteriemias en un hospital de segundo nivel: estudio epidemiológico, análisis de factores pronósticos asociados a mortalidad y estimación de su coste económico.

INTRODUCTION: Bacteraemia (B) accounts for a considerable proportion (0.36%) of all hospital admissions due to infections diseases and it is associated to increased hospital costs. The aim of this study is to describe a cohort of patients with bacteraemia at a second level hospital, to analyze factors associated to mortality and its economical impact during hospital admission. PATIENTS AND METHODS: Observational study of a cohort of adult patients with bacteraemia admitted at a second level hospital during 2010. Data collection from clinical records has been done according to a standard protocol: epidemiological and clinical variables and factors associated to mortality were analysed. Total economical cost per patient was estimated. RESULTS: 148 patients were included: 80 community B (55.4%), 23 health care associated B (15.5%) and 45 nosocomial B (28.5%). The incidence was 9 cases 10.000 persons/year. Mean age was 69 years and the global mortality was 24%. In bivariate analysis smoking, diabetes mellitus, McCabe Jackson score type I-II, Pitt Index ≥ 3, APACHE ≥ 20, Glasgow ≤ 9, shock, respiratory distress, invasive procedures, nosocomial bacteraemia and inadequate empiric or definitive antibiotic treatment were associated to mortality (p<0.05). Factors associated to mortality in multivariate analysis included McCabe Jackson score type I-II (OR 4.95; 95% CI 1.095-22.38), haemodialysis during acute stage (OR 7.8; 95% CI 2.214-27.773) and inadequate empiric antibiotic treatment (OR 7.68; 95% CI 19.82-29.77). Admission economic cost per patient was 9,459 € for community acquired bacteriemia, 5,656 € for health care associated bacteraemia and 41,680€ for nosocomial bacteraemia. CONCLUSIONS: Comorbidity, inadequate empiric antibiotic treatment and haemodialysis during acute phase are statistically significantly in our cohort of patients with bacteraemia.

Bacterial studies of complicated appendicitis over a 20-year period and their impact on empirical antibiotic treatment.

BACKGROUND: Multiresistant bacterial strains tend to develop, especially enterobacteriacae, in intraabdominal infections. The aim of this study was to characterize the evolution of the bacterial biota in complicated appendicitis in children over the past 20 years and their acquired resistance rates to antibiotics. MATERIALS AND METHODS: All pediatric patients admitted in the emergency unit for complicated appendicitis were retrospectively reviewed during 3 periods: 1989 to 1991, 1999 to 2000, and 2009 to 2010. Results of peritoneal swabs were analyzed regarding bacterial species and resistance to antibiotics. Statistical significance was set at P < .05. RESULTS: Thirty-four, 48, and 85 patients from the 3 periods, respectively, were included, with 1 to 6 bacterial strains found in each peritoneal sample. During the first period, 80% of the biota was composed of enterobacteriacae and anaerobes and then decreased to 65%, whereas streptococci levels increased from 0 to 22%. Pansusceptibility rates remained stable (17%, 16.8%, and 15.6% for the 3 periods, respectively). Piperacillin, vancomycin, ticarcillin-clavulanic acid, and fluoroquinolones were associated with increased resistance rates, unlike antibiotic associations currently used as postoperative treatments. CONCLUSION: No significant increase in resistance rates of bacteriacae in complicated appendicitis in children was found over the last 20 years. Empirical antibiotherapy protocols currently recommended remain efficient on this particular biota.

Increased risk of vancomycin-resistant enterococcus (VRE) infection among patients hospitalized for inflammatory bowel disease in the United States.

BACKGROUND: Vancomycin-resistant Enterococcus (VRE) infection has become an increasingly common hospital-acquired infection in U.S. hospitals. Patients with inflammatory bowel disease (IBD) frequently require hospitalization and therefore may be at increased risk of nosocomial infections. METHODS: We used the Nationwide Inpatient Sample (NIS) to identify admissions for IBD (n = 116,842) between 1998 and 2004. We compared the prevalence of VRE in this group to that of non-IBD gastrointestinal (GI) inpatients and general inpatients and assessed for associations between VRE and hospital mortality, length of stay, and total charges. RESULTS: The crude VRE prevalence was 2.1/10,000 in hospitalized IBD patients, 1.3/10,000 in non-IBD GI patients, and 0.9/10,000 in general inpatients. After adjustment for confounders, IBD inpatients were at increased risk of VRE compared to the non-IBD GI (adjusted odds ratio [aOR] 1.65; 95% confidence interval [CI]: 1.03-2.64) and general inpatient (aOR 2.37; 95% CI: 1.31-4.27) groups. Among IBD patients, there was a higher prevalence of VRE infection in those who had surgery (4.4/10,000 versus 1.7/10,000; P < 0.04) and total parenteral nutrition (6.9/10,000 versus 1.8/10,000; P < 0.003). VRE infection was not associated with an increase in mortality (0% versus 0.7%, P = 0.8); however, it was associated with 3-fold higher total hospital charges ($63,517 versus $21,918 USD; P < 0.0001) and increased average length of stay in hospital (16.1 versus 6.1 days; P < 0.0001). CONCLUSIONS: Hospitalized IBD patients have increased susceptibility to VRE that is associated with increased economic burden. This study reinforces the importance of measures to prevent nosocomial infection, particularly in the vulnerable IBD population.

Linezolid: a pharmacoeconomic review of its use in serious Gram-positive infections.

Linezolid (Zyvox), the first available oxazolidinone antibacterial agent, has good activity against Gram-positive pathogens, including multidrug-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Randomised multicentre trials in patients with various types of serious Gram-positive infections showed that clinical cure rates with linezolid were similar to those with vancomycin or teicoplanin. In some subgroup analyses, which must be interpreted with a degree of caution, clinical advantages were noted for linezolid (e.g. versus vancomycin in confirmed MRSA nosocomial pneumonia and MRSA-complicated skin and soft tissue infections). Although generally well tolerated, gastrointestinal adverse effects are relatively common with linezolid and it has been associated with thrombocytopenia and myelosuppression. The oral bioavailability of linezolid is approximately 100%, thus allowing sequential intravenous-to-oral administration without changing the drug or dosage regimen. Healthcare resource use data from various countries indicate that this practical advantage translates into at least a trend towards reduced length of hospital stay compared with vancomycin, which may offset its several-fold higher acquisition cost. Modelled analyses from the US, despite some limitations, indicate that, compared with vancomycin, linezolid is associated with lower total hospitalisation costs for the treatment of patients with cellulitis and has a favourable incremental cost-effectiveness ratio of approximately US30,000 dollars per QALY gained (2001 value) for patients with ventilator-associated pneumonia. Broadly similar results have also been reported in modelled analyses from other countries. In conclusion, for patients with serious Gram-positive infections, including those caused by suspected or proven multidrug-resistant pathogens such as MRSA, linezolid is an effective and generally well tolerated therapeutic option. Linezolid is currently the only antibacterial agent with good activity against MRSA that can be administered orally (as well as intravenously). It may be particularly useful as an alternative to vancomycin in patients who have impaired renal function, poor or no intravenous access, require outpatient therapy, or who have been unable to tolerate glycopeptides. Healthcare resource use studies and pharmacoeconomic analyses generally support the use of linezolid in some subgroups of patients, although results should be interpreted with due consideration of the study limitations.

A consensus statement on empiric therapy for suspected gram-positive infections in surgical patients.

BACKGROUND: Multidrug resistance among gram-positive pathogens in tertiary and other care centers is common. A systematic decision pathway to help select empiric antibiotic therapy for suspected gram-positive postsurgical infections is presented. DATA SOURCES: A Medline search with regard to empiric antibiotic therapy was performed and assessed by the 15-member expert panel. Two separate panel meetings were convened and followed by a writing, editorial, and review process. CONCLUSIONS: The main goal of empiric treatment in postsurgical patients with suspected gram-positive infections is to improve clinical status. Empiric therapy should be initiated at the earliest sign of infection in all critically ill patients. The choice of therapy should flow from beta-lactams to vancomycin to parenteral linezolid or quinupristin-dalfopristin. In patients likely to be discharged, oral linezolid is an option. Antibiotic resistance is an important issue, and in developing treatment algorithms for reduction of resistance, the utility of these new antibiotics may be extended and reduce morbidity and mortality.

Surgical site infections after arthroscopy: Outbreak investigation and case control study.

PURPOSE: The goal of this study was to determine the causes of increased post-arthroscopy surgical site infections (SSIs) and to define risk factors for infection. TYPE OF STUDY: Outbreak investigation and case control study at a university-affiliated community hospital from 1994 to 1996, with surveillance through 1999. METHODS: Demographic, clinical, and microbiological data were collected on 27 post-arthroscopy SSIs from 1994 through 1999. Risk factors for SSI were identified by case-control analysis and presented as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Initial investigation revealed an increased annual rate of post-arthroscopy SSIs in 1995 (1.3%). Infection control deficiencies were identified, and feedback was provided to surgeons and staff. Instrument sterilization was standardized, flash sterilization prohibited, and preoperative shaving discouraged. Case-control analysis of 10 cases (from 1994 to 1996) found a statistically significant increase in risk of SSI with intra-articular corticosteroid joint injection (OR, 9.33; 95% CI, 1.6 to 64.9); other risk factors did not reach statistical significance. SSI rates dropped after feedback and education (0.34% in 1996). Continued surveillance revealed 2 smaller outbreaks, in December 1997 (1997 rate, 1.13%) and September 1998 (1998 rate, 1.09%). Case-control analysis of the 17 cases occurring in 1997 through 1999 was also performed. The 1997 outbreak appeared to be related to preoperative razor shaving (P =.003), which was then prohibited by hospital policy. One scrub nurse was also associated with 75% of these cases, which were culture-positive for coagulase-negative Staphylococcus. The cases in the 1998 outbreak shared prolonged procedure duration and conversion to arthrotomy. Of 27 cases, 24 required repeat hospitalization and repeat surgery, at an average excess cost of $9,154.84 per case. All received prolonged courses of intravenous or oral antibiotics. CONCLUSIONS: Post-arthroscopy SSIs are associated with significant morbidity and cost. Although small numbers make finding statistical significance difficult in case-control studies, infection control and CDC-recommended interventions can lower SSI rates. Careful definitions, ongoing surveillance, and long-term follow-up are helpful in reporting results of infection control interventions.

Health and economic outcomes of vancomycin-resistant enterococci.

BACKGROUND: The health and economic impact of vancomycin-resistant enterococci has not been quantified. METHODS: A retrospective matched cohort study was conducted comparing the outcomes of patients with vancomycin-resistant enterococci (cases) with those of control subjects matched for length of hospital stay until inclusion in the cohort, hospital location, and calendar date. The propensity to be a vancomycin-resistant enterococci case was modeled based on patient characteristics, and included in multivariable models to adjust for confounding. Analyses included the following: (1) conditional logistic regression for mortality, surgery, intensive care unit admission, and discharge to long-term care; (2) linear regression for the logarithm of cost; and (3) accelerated failure time model for length of stay. RESULTS: A total of 233 cases were compared with 647 controls. Groups were similar in age (mean, 62 years), sex (female, 47%), and length of stay before inclusion in the cohort (mean, 8.1 days), but differed in primary diagnosis and comorbidities, past infection or colonization with methicillin sodium-resistant Staphylococcus aureus or Clostridium difficile, and treatment with cephalosporins or metronidazole. These variables were included in the propensity score, which had good to excellent prediction. Outcomes for cases vs controls and adjusted risks (relative risks [RRs]) were as follows: (1) case fatality rate, 17% vs 6% (RR, 2.13; P =.04); (2) length of stay after inclusion in the cohort, 15.1 vs 8.5 days (RR, 1.73; P<.001); (3) hospital costs, $52 449 vs $31 915 (RR, 1.40; P<.001); (4) surgery after inclusion in the cohort, 18% vs 10% (RR, 2.74; P =.001); (5) intensive care unit admission after inclusion in the cohort, 25% vs 14% (RR, 3.47; P<.001); and (6) transfer to an institution, 51% vs 35% (RR, 2.01; P =.001). CONCLUSION: Compared with a matched hospital population, a population with vancomycin-resistant enterococci was associated with severe adverse outcomes: increased mortality, morbidity, and costs.

Costs and savings associated with infection control measures that reduced transmission of vancomycin-resistant enterococci in an endemic setting.

OBJECTIVE: To determine the costs and savings of a 15-component infection control program that reduced transmission of vancomycin-resistant enterococci (VRE) in an endemic setting. DESIGN: Evaluation of costs and savings, using historical control data. SETTING: Adult oncology unit of a 650-bed hospital. PARTICIPANTS: Patients with leukemia, lymphoma, and solid tumors, excluding bone marrow transplant recipients. METHODS: Costs and savings with estimated ranges were calculated. Excess length of stay (LOS) associated with VRE bloodstream infection (BSI) was determined by matching VRE BSI patients with VRE-negative patients by oncology diagnosis. Differences in LOS between the matched groups were evaluated using a mixed-effect analysis of variance linear-regression model. RESULTS: The cost of enhanced infection control strategies for 1 year was $116,515. VRE BSI was associated with an increased LOS of 13.7 days. The savings associated with fewer VRE BSI ($123,081), fewer patients with VRE colonization ($2,755), and reductions in antimicrobial use ($179,997) totaled $305,833. Estimated ranges of costs and savings for enhanced infection control strategies were $97,939 to $148,883 for costs and $271,531 to $421,461 for savings. CONCLUSION: The net savings due to enhanced infection control strategies for 1 year was $189,318. Estimates suggest that these strategies would be cost-beneficial for hospital units where the number of patients with VRE BSI is at least six to nine patients per year or if the savings from fewer VRE BSI patients in combination with decreased antimicrobial use equalled $100,000 to $150,000 per year.

Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care.

PURPOSE: To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia. METHODS: The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions. Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs. RESULTS: Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003). After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01). These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03). Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001). CONCLUSION: Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens. An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.

[Cost of antibiotic therapy in neutropenic patients undergoing peripheral blood stem cell transplantation for breast cancer]. / Coste del tratamiento antibiótico empírico en pacientes neutropénicas sometidas a trasplante de progenitores hematopoyéticos por cáncer de mama.

The increase in pharmaceutical costs, especially for expensive procedures such as bone marrow transplants, has led to the study of the economic impact of febrile neutropenia in peripheral blood stem cell transplantation (PBSCT). We analyzed 89 consecutive patients with breast cancer who underwent PBSCT. All patients developed febrile neutropenia and were administered an empirical intravenous regimen based on the combination of piperacillin-tazobactam and amikacin. We analyzed the direct costs of this treatment and grouped them into drug acquisition cost, administration costs (cost of the additional material), and preparation costs (time employed for the preparation and administration of the drug). We found that the overall cost was $1,110, 65% of which corresponded to the initial therapy and the rest (35%) to the use of additional antibiotics. This higher cost was especially related to the use of vancomycin or teicoplanin (50%). The acquisition costs accounted for 90% of the overall treatment costs. Thirty-six patients (40%) did not need additional antibiotics and the cost in this group was less ($663). We concluded that knowledge of the costs of pharmacological therapy for infection in PBSCT is indispensable for the appropriate development of treatment units, especially in terms of optimizing resources and comparing different therapeutic or prophylactic approaches.

Current attitudes for therapy of febrile neutropenia with consideration to cost-effectiveness.

Febrile neutropenia is a changing syndrome which requires periodic updates as our armamentarium against this condition improves, and the characteristics of the pathogens change. In addition, cost of therapy has become a major issue when designing therapeutic strategies. This article reviews the basis of the current therapeutic approaches to febrile neutropenia, and this information is used to propose an algorithm for the management of this condition taking into consideration, in addition to these medical aspects, cost-effectiveness.

Aetiology, cost of antimicrobial therapy and outcome in neutropenic patients who developed bacteraemia during antimicrobial prophylaxis: a case-control study.

Sixty four episodes of bacteraemia that appeared during antimicrobial prophylaxis with an oral quinolone plus an azole in neutropenic cancer patients were compared with 128 cases of bacteraemia in a cohort of controls matched for age, sex, underlying disease, neutropenia and vascular catheter in situ to assess differences in aetiology, cost of therapy and outcome. Patients who received prophylaxis had breakthrough bacteraemias of a different aetiology compared with the control group: they had significantly fewer multiply-resistant strains (21.9 vs. 51.5, P < 0.04) and a longer afebrile neutropenic period (9.55 days vs. 4.1, P < 0.001). Patients who received prophylaxis also had bacteraemias that were significantly more frequently caused by viridans streptococci (9.4%, vs. 1.7%, P < 0.01), enterococci (15.6% vs. 7.2%, P < 0.05) and Stenotrophomonas maltophilia (17.2% vs. 3.4%, P < 0.01). The cost of antimicrobial therapy per case (37401 SKK (1091 USD) vs. 31808 SKK (899 USD), P < 0.05) was also significantly higher in cases than controls; however, the number of administered antibiotics (4.18 vs. 3.21 per case, P = NS) was similar in both groups. There were no differences in outcome between both groups. However patients who received prophylaxis had significantly longer periods of afebrile neutropenia (9.55 days vs. 4.1, P < 0.001) and bacteraemia developed later than in controls. Also, the incidence of polymicrobial bacteraemia caused by multiresistant strains was lower among cases (21.9 vs. 51.5, P < 0.04).

Cost control of therapy for i.v. catheter infections.

Intravenous catheter sepsis is an important challenge for physicians because it is associated with a high incidence of complications, and treatment can be very costly. Significant complications occur in about 25% of cases and include septic shock, suppurative thrombophlebitis, metastatic infection, and endocarditis. The risk of such complications is increased when catheter removal or appropriate antibiotic therapy is delayed, when Staphylococcus aureus is the pathogen, and probably when a prosthetic heart valve or pulmonary artery catheter is present. The optimum duration of antibiotic therapy for intravenous catheter sepsis has not been established and depends on the pathogen and on the presence of other risk factors for complications. A treatment duration of 1 week may be adequate for pathogens, such as coagulase-negative staphylococci or Candida, that are unlikely to cause complications, while > or = 2 weeks of antibiotic therapy is warranted for S aureus. Recent approaches that may help to reduce costs include shortening the duration of parenteral antibiotic treatment either by giving oral agents for part of the treatment period or by using a synergistic combination of antibiotics. Also, for infections in subcutaneously tunneled catheters, intraluminal administration of small volumes of highly concentrated antibiotics often is an effective alternative to prolonged systemic antibiotic therapy.