Infección de sitio quirúrgico asociada a enterobacterias productoras de carbapenemasas. Un desafío para el cirujano actual / Surgical site infection by carbapenemase-producing Enterobacteriaceae. A challenge for today's surgeons

INTRODUCCIÓN: Las infecciones producidas por enterobacterias productoras de carbapenemasas (EPC) están aumentando drásticamente a nivel mundial, con especial relevancia en pacientes quirúrgicos. El objetivo de este estudio fue analizar el perfil clínico, las complicaciones, el tratamiento, la mortalidad y los costes en pacientes con infección de sitio quirúrgico (ISQ) asociada a EPC tras cirugía abdominal. MÉTODOS: Pacientes con ISQ asociada a EPC tras cirugía abdominal entre enero de 2013 y diciembre de 2018. Se incluyeron aquellos factores y procedimientos previos a la identificación de ISQ, y se realizó un análisis de mortalidad para identificar factores de riesgo en aquellos pacientes con ISQ órgano-cavitaria por EPC tras cirugía abdominal. RESULTADOS: Cincuenta pacientes fueron incluidos: ISQ incisional superficial 50%, ISQ incisional profunda 28%, ISQ órgano-cavitaria (o infección intraabdominal) 70%. Se identificó Klebsiella pneumoniae OXA-48 en el 84%, siendo más frecuentes la cirugía colorrectal (40%) y la pancreática (20%). La sensibilidad antimicrobiana fue: ceftazidima-avibactam 100%, amikacina 91,7%, tigeciclina 89,1%, colistina 70,8%, meropenem 62,8%, imipenem 52,1%. Se utilizó antibioterapia dirigida adecuada en el 86%, incluyendo terapia combinada en el 76%. La mortalidad global a 30 días de la infección intraabdominal fue de un 20%, siendo factores predictores: neoplasia sólida (p = 0,009), metástasis sólida (p = 0,009), shock séptico (p = 0,02), transfusión de hemoderivados (p = 0,03). La mediana global de estancia fue de 45 días (RIC 26-67). La mediana del coste global del ingreso fue 29.946€ (RIC 15.405-47.749). CONCLUSIONES: El perfil del paciente con ISQ causada por EPC incluye múltiples comorbilidades, procedimientos, larga estancia y altos costes asociados. Son predictores de mortalidad en infección intraabdominal la presencia de neoplasia, metástasis, shock séptico o transfusión

INTRODUCTION: Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are dramatically increasing worldwide, with an important impact on surgical patients. Our aim was to assess the clinical profile, outcomes, treatment, mortality and costs of CPE-related surgical site infection (SSI) in patients with abdominal surgery. METHODS: Review of CPE-related SSI in patients with abdominal surgery from January 2013 to December 2018. Patient factors and interventions present previously to the SSI identification were recorded, and a mortality analysis was also performed in patients with abdominal surgery and CPE-related organ/space SSI. RESULTS: Fifty patients were included: superficial incisional SSI 50%, deep incisional SSI 28%, organ/space SSI (or intra-abdominal infection) 70%. Klebsiella pneumoniae OXA-48 was present in 84%, and the most frequent were colorectal surgery (40%) and pancreatic surgery (20%). The antimicrobial susceptibility was: ceftazidime-avibactam 100%, amikacin 91.7%, tigecycline 89.1%, colistin 70.8%, meropenem 62.8%, imipenem 52.1%. An appropriate definitive antimicrobial treatment was administered in 86%, using a combined scheme in 76%. Global 30-day mortality rate for intra-abdominal infection was 20%, and mortality-related factors were: solid tumour (P = .009), solid metastasis (P = .009), septic shock (P = .02), blood transfusions (P = .03). Median global stay was 45 (IQR 26-67) days. Median global cost of hospitalization was €29,946 (IQR 15,405-47,749). CONCLUSIONS: The clinical profile of patients with CPE-related SSI associates several comorbidities, interventions, prolonged stay and elevated costs. Mortality-related factors in intra-abdominal infection are solid tumour, metastasis, septic shock or blood transfusions

Prevalence, etiology, and economic impact of clinical mastitis on large dairy farms in China.

This study investigated the continuous monthly prevalence of bovine clinical mastitis (CM) and the distribution of causative pathogens among 36,619 CM milk samples from large dairy farms across seven Chinese provinces from 2015 to 2017 using data from routine CM recording systems. Based on treatment period and cost per cow, withdrawal period, daily milk production, and milk value data from each farm in 2017, we calculated the economic impact of CM at the farm level with 2578-9044 lactating cows per farm. Results showed a wide variation in monthly prevalence of CM (0.6 %-18.2 %) among the seven farms over the study period, indicating regional and temporal differences in the occurrence of CM in China. Enterobacteriaceae were the predominant pathogens across all farms from six provinces except Shandong, in which the Streptococcus spp. was the most prevalent. However, the distribution of various Enterobacteriaceae species differed among farms, and Streptococcus species distribution was strongly associated (Pearson's coefficient, 68.4 %) with location. Monthly economic losses associated with CM showed clear variation, ranging from 12,000-76,000 USD/farm/month. Sensitivity analysis showed that economic loss at the farm level was most sensitive to variation in the prevalence of CM, followed by antibiotic treatment period and daily milk production per cow. To our knowledge, this is the longest running study of CM and the first estimation of its economic impacts in China. Our findings highlight the considerable costs associated with mastitis, and indicate that preventive measures and regional and timely treatment of CM are needed.

Surgical site infection by carbapenemase-producing Enterobacteriaceae. A challenge for today's surgeons. / Infección de sitio quirúrgico asociada a enterobacterias productoras de carbapenemasas. Un desafío para el cirujano actual.

INTRODUCTION: Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are dramatically increasing worldwide, with an important impact on surgical patients. Our aim was to assess the clinical profile, outcomes, treatment, mortality and costs of CPE-related surgical site infection (SSI) in patients with abdominal surgery. METHODS: Review of CPE-related SSI in patients with abdominal surgery from January 2013 to December 2018. Patient factors and interventions present previously to the SSI identification were recorded, and a mortality analysis was also performed in patients with abdominal surgery and CPE-related organ/space SSI. RESULTS: Fifty patients were included: superficial incisional SSI 50%, deep incisional SSI 28%, organ/space SSI (or intra-abdominal infection) 70%. Klebsiella pneumoniae OXA-48 was present in 84%, and the most frequent were colorectal surgery (40%) and pancreatic surgery (20%). The antimicrobial susceptibility was: ceftazidime-avibactam 100%, amikacin 91.7%, tigecycline 89.1%, colistin 70.8%, meropenem 62.8%, imipenem 52.1%. An appropriate definitive antimicrobial treatment was administered in 86%, using a combined scheme in 76%. Global 30-day mortality rate for intra-abdominal infection was 20%, and mortality-related factors were: solid tumour (P=.009), solid metastasis (P=.009), septic shock (P=.02), blood transfusions (P=.03). Median global stay was 45 (IQR 26-67) days. Median global cost of hospitalization was €29,946 (IQR 15,405-47,749). CONCLUSIONS: The clinical profile of patients with CPE-related SSI associates several comorbidities, interventions, prolonged stay and elevated costs. Mortality-related factors in intra-abdominal infection are solid tumour, metastasis, septic shock or blood transfusions.

Polymyxin B and colistin-the economic burden of nephrotoxicity against multidrug resistant bacteria.

BACKGROUND: Polymyxin B and colistin are nephrotoxic drugs used in the treatment of carbapenem-resistant Enterobacteriaceae. The aim of this study is to evaluate the burden of costs due to polymyxin associated AKI and propose a simulated break-even price for new therapies. METHODS: The pharmacoeconomic model is based on two large cross-sectional studies of polymyxin nephrotoxicity. Total direct costs in patients with and without renal failure were compared. The direct cost of each hemodialysis section (USD82.94) and daily hospital charges (USD934.85) were based on the values used in a major public hospital in the city where the clinical study was performed. The break-even price of new drugs was simulated considering eventual new drugs as effective as polymyxins, but less nephrotoxic in different percentages. Outcomes of patients after hospital discharge were not evaluated. RESULTS: Total direct cost of the group of patients who survived without AKI was significantly lower than total direct cost of the groups either with AKI or the group who died without AKI. There was a tendency of even higher costs in those who died with AKI and dialysis. Direct cost of hemodialysis was not as important as the longer hospitalization after sepsis. Considering daily cost of polymyxin is USD60, drugs with 50% less AKI could be considered cost-beneficial if the daily cost is lower than USD160. CONCLUSIONS: AKI in patients with carbapenem-resistant Enterobacteriaceae treated with polymyxin increases both length of stay in hospital and total costs.

Societal willingness to pay to avoid mortality and morbidity from Clostridioides difficile and carbapenem-resistant Enterobacteriaceae infections in the United States.

BACKGROUND: Clostridioides difficile infection (CDI) is among the most common health care-associated infections in the United States and is increasingly affecting the elderly. Although carbapenem-resistant Enterobacteriaceae (CRE) infections are still relatively uncommon, there are reported increases in the rate of infection for certain strains, such as Klebsiella pneumoniae. This study examines the burden of mortality and morbidity for CDI and CRE infections in the United States and estimates the societal willingness to pay to avoid them. METHODS: We use an analytic model to estimate the number of incident cases and associated health outcomes for CDI and CRE infections. RESULTS: The number of CDI and CRE infection incident cases in the United States in 2016, is estimated at 468,567 and 9,620, respectively. These infections result in a total of 17,630 estimated deaths and 8,624 lost quality-adjusted life years among patients who survive per year. CONCLUSIONS: Given the significant mortality and morbidity from these infections, the estimated societal willingness to pay to avoid them is high at $176.7 billion per year, of which 93.9% ($166.0 billion) is for CDI. Our estimates far exceed the medical care costs for CDIs and CRE infections reported in the literature despite not capturing the additional costs borne by third-party payers. As incident cases increase or resistant strains develop, the societal willingness to pay is also expected to increase.

Fast and expensive (PCR) or cheap and slow (culture)? A mathematical modelling study to explore screening for carbapenem resistance in UK hospitals.

BACKGROUND: Enterobacteriaceae are a common cause of hospital infections. Carbapenems are a clinically effective treatment of such infections. However, resistance is on the rise. In particular, carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are increasingly common. In order to limit spread in clinical settings, screening and isolation is being recommended, but many different screening methods are available. We aimed to compare the impact and costs of three algorithms for detecting CP-CRE carriage. METHODS: We developed an individual-based simulation model to compare three screening algorithms using data from a UK National Health Service (NHS) trust. The first algorithm, "Direct PCR", was highly sensitive/specific and quick (half a day), but expensive. The second, "Culture + PCR", was relatively sensitive/specific but slower, requiring 2.5 days. A third algorithm, "PHE", repeated the "Culture + PCR" three times with an additional PCR. Scenario analysis was used to compare several levels of CP-CRE prevalence and coverage of screening, different specialities as well as isolation strategies. Our outcomes were (1) days that a patient with CP-CRE was not detected and hence not isolated ("days at risk"), (2) isolation bed days, (3) total costs and (4) mean cost per CP-CRE risk day averted per year. We also explored limited isolation bed day capacity. RESULTS: We found that although a Direct PCR algorithm would reduce the number of CP-CRE days at risk, the mean cost per CP-CRE risk day averted per year was substantially higher than for a Culture + PCR algorithm. For example, in our model of an intensive care unit, during a year with a 1.6% CP-CRE prevalence and 63% screening coverage, there were 508 (standard deviation 15), 642 (14) and 655 (14) days at risk under screening algorithms Direct PCR, Culture + PCR and PHE respectively, with mean costs per risk day averted of £192, £61 and £79. These results were robust to sensitivity analyses. CONCLUSIONS: Our results indicate that a Culture + PCR algorithm provides the optimal balance of cost and risk days averted, at varying isolation, prevalence and screening coverage scenarios. Findings from this study will help clinical organisations determine the optimal screening approach for CP-CRE, balancing risk and resources.

The Economic Value of the Centers for Disease Control and Prevention Carbapenem-Resistant Enterobacteriaceae Toolkit.

OBJECTIVEWhile previous work showed that the Centers for Disease Control and Prevention toolkit for carbapenem-resistant Enterobacteriaceae (CRE) can reduce spread regionally, these interventions are costly, and decisions makers want to know whether and when economic benefits occur.DESIGNEconomic analysisSETTINGOrange County, CaliforniaMETHODSUsing our Regional Healthcare Ecosystem Analyst (RHEA)-generated agent-based model of all inpatient healthcare facilities, we simulated the implementation of the CRE toolkit (active screening of interfacility transfers) in different ways and estimated their economic impacts under various circumstances.RESULTSCompared to routine control measures, screening generated cost savings by year 1 when hospitals implemented screening after identifying ≤20 CRE cases (saving $2,000-$9,000) and by year 7 if all hospitals implemented in a regional coordinated manner after 1 hospital identified a CRE case (hospital perspective). Cost savings was achieved only if hospitals independently screened after identifying 10 cases (year 1, third-party payer perspective). Cost savings was achieved by year 1 if hospitals independently screened after identifying 1 CRE case and by year 3 if all hospitals coordinated and screened after 1 hospital identified 1 case (societal perspective). After a few years, all strategies cost less and have positive health effects compared to routine control measures; most strategies generate a positive cost-benefit each year.CONCLUSIONSActive screening of interfacility transfers garnered cost savings in year 1 of implementation when hospitals acted independently and by year 3 if all hospitals collectively implemented the toolkit in a coordinated manner. Despite taking longer to manifest, coordinated regional control resulted in greater savings over time.Infect Control Hosp Epidemiol 2018;39:516-524.

Urinary tract infections caused by ESBL-producing Enterobacteriaceae in renal transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Urinary tract infections (UTIs) are the most common infectious complications among renal transplant recipients (RTR). UTIs caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) have been associated with inferior clinical outcomes and increased financial burden. METHODS: We performed a systematic review and meta-analysis by searching through the PubMed and EMBASE databases (to May 20, 2016) and identifying studies that reported data on the number of RTR who developed an ESBL-PE UTI. RESULTS: Our analysis included seven studies, out of 357 non-duplicate articles, that provided data on 2824 patients. Among them, 10% (95% confidence interval [CI] 4%-17%) developed an ESBL-PE UTI over their follow-up periods. The proportion of RTR affected by an ESBL-PE UTI was 2% in North America (95% CI 1%-3%), 5% in Europe (95% CI 4%-6%), 17% in South America (95% CI 10%-27%), and 33% in Asia (95% CI 27%-41%). In addition, patients affected with an ESBL-PE UTI were 2.75-times (95% CI 1.97-3.83) more likely to suffer a recurrent UTI. CONCLUSIONS: Based on a limited number of studies, one in 10 RTR will develop a UTI caused by an ESBL-PE, and these patients face an almost 3 times greater risk of recurrence. A more rigorous monitoring of RTR, both during and after resolution of their infection, should be evaluated in order to reduce the incidence and the clinical impact of these resistant infections.

Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis.

BACKGROUND: Drug resistance among gram-negative pathogens is a risk factor for inappropriate empiric treatment (IET), which in turn increases the risk for mortality. We explored the impact of carbapenem-resistant Enterobacteriaceae (CRE) on the risk of IET and of IET on outcomes in patients with Enterobacteriaceae infections. METHODS: We conducted a retrospective cohort study in Premier Perspective database (2009-2013) of 175 US hospitals. We included all adult patients with community-onset culture-positive urinary tract infection (UTI), pneumonia, or sepsis as a principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure, treated with antibiotics within 2 days of admission. We employed regression modeling to compute adjusted association of presence of CRE with risk of receiving IET, and of IET on hospital mortality, length of stay (LOS) and costs. RESULTS: Among 40,137 patients presenting to the hospital with an Enterobacteriaceae UTI, pneumonia or sepsis, 1227 (3.1%) were CRE. In both groups, the majority of the cases were UTI (51.4% CRE and 54.3% non-CRE). Those with CRE were younger (66.6+/-15.3 vs. 69.1+/-15.9 years, p < 0.001), and more likely to be African-American (19.7% vs. 14.0%, p < 0.001) than those with non-CRE. Both chronic (Charlson score 2.0+/-2.0 vs. 1.9+/-2.1, p = 0.009) and acute (by day 2: ICU 56.3% vs. 30.4%, p < 0.001, and mechanical ventilation 35.8% vs. 11.7%, p < 0.001) illness burdens were higher among CRE than non-CRE subjects, respectively. CRE patients were 3× more likely to receive IET than non-CRE (46.5% vs. 11.8%, p < 0.001). In a regression model CRE was a strong predictor of receiving IET (adjusted relative risk ratio 3.95, 95% confidence interval 3.5 to 4.5, p < 0.001). In turn, IET was associated with an adjusted rise in mortality of 12% (95% confidence interval 3% to 23%), and an excess of 5.2 days (95% confidence interval 4.8, 5.6, p < 0.001) LOS and $10,312 (95% confidence interval $9497, $11,126, p < 0.001) in costs. CONCLUSIONS: In this large US database, the prevalence of CRE among patients with Enterobacteriaceae UTI, pneumonia or sepsis was comparable to other national estimates. Infection with CRE was associated with a four-fold increased risk of receiving IET, which in turn increased mortality, LOS and costs.

Potential economic burden of carbapenem-resistant Enterobacteriaceae (CRE) in the United States.

OBJECTIVES: The Centers for Disease Control and Prevention considers carbapenem-resistant Enterobacteriaceae (CRE) an urgent public health threat; however, its economic burden is unknown. METHODS: We developed a CRE clinical and economics outcomes model to determine the cost of CRE infection from the hospital, third-party payer, and societal, perspectives and to evaluate the health and economic burden of CRE to the USA. RESULTS: Depending on the infection type, the median cost of a single CRE infection can range from $22 484 to $66 031 for hospitals, $10 440 to $31 621 for third-party payers, and $37 778 to $83 512 for society. An infection incidence of 2.93 per 100 000 population in the USA (9418 infections) would cost hospitals $275 million (95% CR $217-334 million), third-party payers $147 million (95% CR $129-172 million), and society $553 million (95% CR $303-1593 million) with a 25% attributable mortality, and would result in the loss of 8841 (95% CR 5805-12 420) quality-adjusted life years. An incidence of 15 per 100 000 (48 213 infections) would cost hospitals $1.4 billion (95% CR $1.1-1.7 billion), third-party payers $0.8 billion (95% CR $0.6-0.8 billion), and society $2.8 billion (95% CR $1.6-8.2 billion), and result in the loss of 45 261 quality-adjusted life years. CONCLUSIONS: The cost of CRE is higher than the annual cost of many chronic diseases and of many acute diseases. Costs rise proportionally with the incidence of CRE, increasing by 2.0 times, 3.4 times, and 5.1 times for incidence rates of 6, 10, and 15 per 100 000 persons.

The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study.

We performed a multicentre retrospective cohort study including 606,649 acute inpatient episodes at 10 European hospitals in 2010 and 2011 to estimate the impact of antimicrobial resistance on hospital mortality, excess length of stay (LOS) and cost. Bloodstream infections (BSI) caused by third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE), meticillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) increased the daily risk of hospital death (adjusted hazard ratio (HR) = 1.80; 95% confidence interval (CI): 1.34-2.42, HR = 1.81; 95% CI: 1.49-2.20 and HR = 2.42; 95% CI: 1.66-3.51, respectively) and prolonged LOS (9.3 days; 95% CI: 9.2-9.4, 11.5 days; 95% CI: 11.5-11.6 and 13.3 days; 95% CI: 13.2-13.4, respectively). BSI with third-generation cephalosporin-susceptible Enterobacteriaceae (3GCSE) significantly increased LOS (5.9 days; 95% CI: 5.8-5.9) but not hazard of death (1.16; 95% CI: 0.98-1.36). 3GCRE significantly increased the hazard of death (1.63; 95% CI: 1.13-2.35), excess LOS (4.9 days; 95% CI: 1.1-8.7) and cost compared with susceptible strains, whereas meticillin resistance did not. The annual cost of 3GCRE BSI was higher than of MRSA BSI. While BSI with S. aureus had greater impact on mortality, excess LOS and cost than Enterobacteriaceae per infection, the impact of antimicrobial resistance was greater for Enterobacteriaceae.

Factors associated with marketable milk production recovery after treatment of naturally occurring acute coliform mastitis.

Milk production loss after recovery from acute coliform mastitis causes major economic losses for dairy industries. Declines in milk production and composition are caused by multiple factors, including cow factors, microorganisms and treatments, but the influence of each factor has not been determined. To investigate risk factors for milk loss after treatment for acute coliform mastitis, multiple logistic regression analyses were conducted in 53 clinical cases. Systemic administration of fluoroquinolone was significantly associated with recovery of marketable milk production. The time to slaughter was significantly shorter in cows with complete loss of quarter milk production than in cows that produced marketable milk. In this study, we identified factors associated with increased risk of milk production loss.

Characteristics and costs of carbapenemase-producing enterobacteria carriers (2012/2013).

OBJECTIVES: We had for aim to determine the characteristics of carbapenemase-producing enterobacteria (CPE) carriers and to assess the economic impact of isolation measures leading to loss of activity (closed beds, prolonged hospital stays) and additional personnel hours. PATIENTS AND METHODS: We conducted a retrospective study for 2years (2012/2013), in a French general hospital, focusing on CPE carriers with clinical case description. The costs were estimated by comparing the activity of concerned units (excluding the ICU) during periods with CPE carriers or contacts, during the same periods of the year (n-1), plus additional hours and rectal swabs. RESULTS: Sixteen EPC carriers were identified: 10 men and 6 women, 65±10years of age. Seven patients acquired EPC in hospital during 2 outbreaks in 2012. Four patients presented with an infection (peritonitis, catheter infection, and 2 cases of obstructive pyelonephritis) with a favorable outcome. The median length of stay was 21days [4,150]. Six patients died, 1 death was indirectly due to CPE because of inappropriate empiric antibiotic therapy. A decrease in activity was observed compared to the previous year with an estimated 547,303€ loss. The 1779 additional hours cost 63,870€, and 716 screening samples cost 30,931€. The total additional cost was estimated at 642,104€ for the institution. CONCLUSIONS: Specialized teams for CPE carriers and isolation of contact patients, required to avoid/control epidemics, have an important additional cost. An appreciation of their support is needed, as well as participation of rehabilitation units.

Burden of bloodstream infection caused by extended-spectrum ß-lactamase-producing enterobacteriaceae determined using multistate modeling at a Swiss University Hospital and a nationwide predictive model.

OBJECTIVE: To obtain an unbiased estimate of the excess hospital length of stay (LOS) and cost attributable to extended-spectrum ß-lactamase (ESBL) positivity in bloodstream infections (BSIs) due to Enterobacteriaceae. DESIGN: Retrospective cohort study. SETTING: A 2,200-bed academic medical center in Geneva, Switzerland. PATIENTS: Patients admitted during 2009. METHODS: We used multistate modeling and Cox proportional hazards models to determine the excess LOS and adjusted end-of-LOS hazard ratio (HR) for ESBL-positive and ESBL-negative BSI. We estimated economic burden as the product of excess LOS and average bed-day cost. Patient-level accounting data provided a complementary analysis of economic burden. A predictive model was fitted to national surveillance data. RESULTS: Thirty ESBL-positive and 96 ESBL-negative BSI cases were included. The excess LOS attributable to ESBL-positive and ESBL-negative BSI was 9.4 (95% confidence interval [CI], 0.4-18.4) and 2.6 (95% CI, 0.7-5.9) days, respectively. ESBL positivity was therefore associated with 6.8 excess days and CHF 9,473 per BSI. The adjusted end-of-LOS HRs for ESBL-positive and ESBL-negative BSI were 0.62 (95% CI, 0.43-0.89) and 0.90 (95% CI, 0.74-1.10), respectively. After reimbursement, the average financial loss per acute care episode in ESBL-positive BSI, ESBL-negative BSI, and control cohorts was CHF 48,674, 48,131, and 13,532, respectively. Our predictive model estimated that the nationwide cost of third-generation cephalosporin resistance would increase from CHF 2,084,000 in 2010 to CHF 3,526,000 in 2015. CONCLUSIONS: This is the first hospital-wide analysis of excess LOS attributable to ESBL positivity determined using multistate modeling to avoid time-dependent bias. These results may inform health-economic evaluations of interventions targeting ESBL control.

[Gut bacteria and antimicrobial resistance--what to worry about]. / Suolistoperäiset moniresistentit bakteerit kliinikon huolenaiheena.

Gram negative and anaerobic bacteria from gut microbiota are important pathogens both in community-acquired and hospital infections. Escherichia coli is the the most common cause of adult bacteraemias in Finland. Antimicrobial resistance in these bacteria is a threatening phenomenon. Enterobacteriacae producing extended spectrum beta-lactamase (ESBL) have spead worldwide. The use of antimicrobial agents shifts the balance in gut microbiota and induces and selects bacterial resistance. When resistant bacteria cause infections, empiric antimicrobial therapy may not cover them, which may increase lenght of hospital stay, costs and mortality due to infections.

Infections with extended-spectrum beta-lactamase-producing enterobacteriaceae: changing epidemiology and drug treatment choices.

Since 2000, Escherichia coli producing CTX-M enzymes (especially CTX-M-15) have emerged worldwide as important causes of community-onset urinary tract infections (UTIs) and bloodstream infections due to extended-spectrum beta-lactamase (ESBL)-producing bacteria. Molecular epidemiology studies suggested that the sudden worldwide increase of CTX-M-15-producing E. coli is mostly due to a single clone named ST131 and that foreign travel to high-risk areas such as the Indian subcontinent might in part play a role in the spread of this clone across different continents. Empirical antibacterial coverage for these resistant organisms should be considered in community patients presenting with sepsis involving the urinary tract especially if a patient recently travelled to a high-risk area. Infections due to ESBL-producing Enterobacteriaceae are associated with a delay in initiation of appropriate antibacterial therapy, which consequently prolongs hospital stays and increases hospital costs. Failure to initiate appropriate antibacterial therapy from the start appears to be responsible for higher patient mortality. The carbapenems are widely regarded as the drugs of choice for the treatment of severe infections due to ESBL-producing Enterobacteriaceae, although comparative clinical trials are lacking. Agents that may be useful for the treatment of ESBL-associated UTIs include fosfomycin, nitrofurantoin and temocillin. If this emerging public health threat is ignored, it is possible that clinicians may be forced in the near future to use the carbapenems as the first choice for empirical treatment of serious infections associated with UTIs originating from the community.

Economic consequences of failure of initial antibiotic therapy in hospitalized adults with complicated intra-abdominal infections.

BACKGROUND: Initial antibiotic therapy in hospitalized adults with complicated intra-abdominal infection (cIAI) usually is empiric. We explored the economic consequences of failure of such therapy in this patient population. METHODS: Using a large U.S. multi-institutional database, we identified all hospitalized adults admitted between April 1, 2003, and March 31, 2004; who had any cIAI; underwent laparotomy, laparoscopy, or percutaneous drainage of an intra-abdominal abscess ("surgery"); and received intravenous (IV) antibiotics. Initial therapy was characterized in terms of all IV antibiotics received, on the day of or one day before initial surgery. Antibiotic failure was designated on the basis of the need for reoperation or receipt of other IV antibiotics postoperatively. Switches to narrower spectrum agents and changes in regimen prior to discharge with no other evidence of clinical failure were not counted as antibiotic failures. Using multivariable linear regression, duration of IV antibiotic therapy, hospital length of stay, and total inpatient charges were compared between patients who did and did not fail initial therapy. Mortality was compared using multivariable logistic regression. RESULTS: Among 6,056 patients who met the study entrance criteria, 22.4% failed initial antibiotic therapy. Patients who failed received an additional 5.6 days of IV antibiotic therapy (10.4 total days [95% confidence interval 10.1, 10.8] days vs. 4.8 total days [4.8, 4.9] for those not failing), were hospitalized an additional 4.6 days (11.6 total days [11.3, 11.9] vs. 6.9 total days [6.8, 7.0], respectively), and incurred $6,368 in additional inpatient charges ($16,520 [$16,131, $16,919] vs. $10,152 [$10,027, $10,280]) (all, p < 0.01). They also were more likely to die in the hospital (9.5% vs. 1.3%; multivariable odds ratio 3.58 [95% confidence interval 2.53, 5.06]). CONCLUSIONS: Failure of initial IV antibiotic therapy in hospitalized adults with cIAIs is associated with longer hospitalization, higher hospital charges, and a higher mortality rate.

Development of a travelers' diarrhea vaccine for the military: how much is an ounce of prevention really worth?

Infectious diarrhea is one of the many threats to the deployed military, and given limited resources, a decision to pursue a vaccine acquisition strategy should be based on best evidence that weighs costs and benefits compared to alternatives. An economic model was developed to estimate the marginal cost to avert a duty day lost due to diarrhea for a vaccine acquisition strategy compared to current clinical management, for both multiplex and pathogen-specific vaccines. Vaccines against Campylobacter and enterotoxigenic Escherichia coli appeared to be more favorable than a Shigella vaccine. This model provides an evidence-based decision tool to support prioritization in vaccine development.