Carbapenem Prescription Research Articles

Ciprofloxacin prophylaxis in high risk neutropenic patients: effects on outcomes, antimicrobial therapy and resistance.

BackgroundThe use of quinolone prophylaxis in high-risk neutropenic patients is considered standard of care but the development of resistance is a concern. Previous studies have focused mainly on quinolone resistance among patients receiving prophylaxis, with very few data reporting its impact on the hospital microbial epidemiology.MethodsWe analyzed a cohort of 329 episodes of chemotherapy-induced neutropenia in adults, and compared two periods: 2005 (period 1, no prophylaxis, n=110) and 2006-2008 (period 2, ciprofloxacin prophylaxis, n=219). Outcomes analyzed were the frequency of febrile neutropenia, bacteremia, duration of antibiotic therapy and hospitalization, and antimicrobial resistance to ciprofloxacin and extended-spectrum beta-lactamase [ESBL] production. We analyzed resistance rates (by patients-day) in the cohort, as well as in other patients (neutropenic and non-neutropenic, 11,975 patients-day) admitted to the hematology unit in the same period, taking into consideration the general resistance patterns in the hospital.ResultsQuinolone prophylaxis (period 2) resulted in fewer episodes of febrile neutropenia (159/219 [73%] vs. 102/110 [93%], Chi-square 18.09, p = 0.00002), and bacteremia (49/219 [22] vs. 36/110 [33%], Chi-square 4.10, p = 0.04), shorter duration of antibiotic therapy (p = 0.0002) and hospitalization (p = 0.002), but more frequent use of carbapenems (79/219 [36%] vs. 15/110 [14%], Chi-square 18.06, p = 0.0002). In addition, period 2 was associated with higher rates of quinolone resistance (6.77 vs. 3.02 per 1,000 patients-day, p = 0.03). The rate of ESBL-producing enterobacteria in the two periods was slightly higher in patients receiving quinolone prophylaxis (1.27 vs. 0.38 per 1,000 patients-day, p = 0.26) as well as in the hematology unit overall (1.59 vs. 0.53 per 1,000 patients-day, p = 0.08), but remained stable in the whole hospital (0.53 vs. 0.56 per 1,000 patients-day, p = 0.74).ConclusionsCiprofloxacin prophylaxis was beneficial in high risk neutropenic patients, but important modifications in the prescription of carbapenems and on antimicrobial resistance patterns of isolates were observed. The importance of hospital or ward ecology must be taken into account when deciding for quinolone prophylaxis in high-risk neutropenic patients.

Impact of a program combining pre-authorization requirement and post-prescription review of carbapenems: an interrupted time-series analysis

The objective of this study was to assess the impact on carbapenems use of a program combining pre-authorization requirement and systematic post-prescription review of carbapenems prescriptions. The program was implemented in a 1,230-bed teaching tertiary hospital. Monthly carbapenems consumption was analyzed using a controlled interrupted time-series method and compared to that of vancomycin before and after implementation of the intervention. Compared to the pre-intervention period (14 monthly points), a significant and sustained decrease of carbapenems consumption [1.66 defined daily doses (DDD)/1,000 patient-days; p = 0.048] was observed during the intervention period (12 monthly points), despite an increasing trend in incidence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) isolates (0.02/1,000 patient-days per month; p = 0.093). As expected, vancomycin consumption was unaffected by the intervention. A total of 337 prescriptions were reviewed in the intervention period; most were microbiologically documented (81.3%; ESBL-PE: 39.2%). Three of four (76.6%) carbapenems prescriptions were modified within a median [interquartile range] of 2 [1; 4] days, either after infectious disease physician (IDP) advice (48.4%) or by ward physicians (28.2%). Most changes included de-escalating (52.2%) or reducing the planned duration (22.2%), which resulted in a median duration of treatment of only 3 [2; 7] days. The median length of stay and mortality rate were not influenced by the intervention. This reasonably practicable antimicrobial stewardship program including controlled delivery and systematic reevaluation of carbapenems prescriptions was able to reduce their use in our hospital, despite a rising ESBL-PE incidence.

Carbapenem Restriction and its Effect on Bacterial Resistance in an Intensive Care unit of a Teaching Hospital.

Development of antibiotic resistance in Intensive Care Units (ICUs) is a worldwide problem. The purpose of this study was to evaluate the effect of an antibiotic stewardship program (ASP) by carbapenems restriction on gram-negative antimicrobial resistance in ICU. The study was designed in a 21 bedded general ICU of a teaching hospital with two wings (one and two) in Tehran, Iran. Carbapenem prescription in ICU1 was restricted to only the culture proven multi-drug-resistant bacteria with the absence of sensitivity to other antimicrobial agents. Carbapenem had to be prescribed by a trained ICU physician with close consultation with infectious disease specialist and the clinical pharmacist posted in ICU. Post-prescription reviews and de-escalations were carried out by the same team on regular basis. Restriction policy was commenced in January 2011 in ICU1. All documented infections and resistance patterns of isolated pathogens were recorded in both ICUs during two periods of 6 months before and 9 months after restriction policy implementation. During this study bacterial growth was detected in 51.5% of 1601 samples. Carbapenem administration was decreased from 6.86 to 2.75 DDD/100 patients day (60% decreases) pre-restriction and post-restriction respectively. Significant increase in sensitivity of pseudomonas to imipenem was observed in ICU1 comparing with pre-restriction period six months post restriction (p = 0.000). Sensitivity of Klebsiella and Acinetobacter to imipenem did not change significantly during the study period. Our study demonstrated that restriction of carbapenems can increase sensitivity of P. aeroginosa to imipenem.

Appropriate use of carbapenems in the Besançon university hospital

IntroductionThe excessive and inappropriate use of carbapenems is responsible for the development of resistance. The scientific community has been requiring caution and using these agents in specific cases only. ObjectivesThe authors had for aim to evaluate the appropriate use of carbapenems in a French university hospital. DesignA retrospective survey was made over two months as a clinical audit to assess professional practices. The evaluation criteria for this audit were: the appropriateness of the indication, the possibility of alternative therapeutic strategies, the choice of an antibiotic combination, duration of treatment and dosage. ResultsDuring the audit period, 103 carbapenem prescriptions were included. Ninety-nine cases were analyzed. Among the carbapenem prescriptions, 28.3% (28/99) did not meet the criterion “appropriateness of the indication”. Carbapenems were mostly prescribed empirically (60/99 [60%]) and most often for lung infections or nosocomial urinary tract infections. Finally, 66.7% (66/99) of all prescriptions were considered inappropriate for at least one criterion. The rate of inappropriateness ranged around 30% for each criterion. ConclusionsThis study allowed us to assess professional practices for carbapenem prescriptions. The overall rate of inappropriateness was quite important. Carbapenems were not always used appropriately. These findings highlight the need of new regional guidelines and regular updating of local best practices recommendations. Finally, a stricter validation of carbapenem prescriptions will be implemented at the hospital pharmacy level.

Correlation between Carbapenem Prescription Trends and Imipenem Resistance inAcinetobacter baumanniiat an Intensive Care Unit between 2006 and 2010

Correlation between Carbapenem Prescription Trends and Imipenem Resistance in<i>Acinetobacter baumannii</i>at an Intensive Care Unit between 2006 and 2010

Determinants of prescription and choice of empirical therapy for hospital-acquired and ventilator-associated pneumonia

The objectives of this study were to assess the determinants of empirical antibiotic choice, prescription patterns and outcomes in patients with hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in Europe. We performed a prospective, observational cohort study in 27 intensive care units (ICUs) from nine European countries. 100 consecutive patients on mechanical ventilation for HAP, on mechanical ventilation>48 h or with VAP were enrolled per ICU. Admission category, sickness severity and Acinetobacter spp. prevalence>10% in pneumonia episodes determined antibiotic empirical choice. Trauma patients were more often prescribed non-anti-Pseudomonas cephalosporins (OR 2.68, 95% CI 1.50-4.78). Surgical patients received less aminoglycosides (OR 0.26, 95% CI 0.14-0.49). A significant correlation (p<0.01) was found between Simplified Acute Physiology Score II score and carbapenem prescription. Basal Acinetobacter spp. prevalence>10% dramatically increased the prescription of carbapenems (OR 3.5, 95% CI 2.0-6.1) and colistin (OR 115.7, 95% CI 6.9-1,930.9). Appropriate empirical antibiotics decreased ICU length of stay by 6 days (26.3±19.8 days versus 32.8±29.4 days; p=0.04). The antibiotics that were prescribed most were carbapenems, piperacillin/tazobactam and quinolones. Median (interquartile range) duration of antibiotic therapy was 9 (6-12) days. Anti-methicillin-resistant Staphylococcus aureus agents were prescribed in 38.4% of VAP episodes. Admission category, sickness severity and basal Acinetobacter prevalence>10% in pneumonia episodes were the major determinants of antibiotic choice at the bedside. Across Europe, carbapenems were the antibiotic most prescribed for HAP/VAP.

Limited efficacy of a nonrestricted intervention on antimicrobial prescription of commonly used antibiotics in the hospital setting: results of a randomized controlled trial

Most interventions aimed at diminishing the use of antimicrobials in hospitals have focussed on newly introduced antibiotics and very few have been randomly controlled. We evaluated the impact on antibiotic consumption of an intervention without restrictions in antibiotic use, focussed on commonly used antibiotics with a controlled randomized trial. All new prescriptions of levofloxacin, carbapenems, or vancomycin in hospitalized patients were randomized to an intervention or a control group. Intervention consisted of an antibiotic regimen counselling targeted to match local antibiotic guidelines, performed using only patients' charts. Clinical charts of patients assigned to the control group were reviewed daily by a pharmacist. The primary endpoint was a reduction in consumption of the targeted antibiotics. Two hundred seventy-eight prescriptions corresponding to 253 patients were included: 146 were assigned to the intervention and 132 to the control group. Total consumption of the targeted antibiotics (median [IQR]) was slightly lower in the intervention (8 [4-12] defined daily doses [DDDs] per patient) than in the control group (10 [6-16] DDDs per patient; p = 0.04). No differences in number of DDDs were observed when antibiotics of substitution were included (11.05 [6-18.2] vs 10 [6-16.5] in the intervention and control groups, respectively, p = 0.13). The total number of days on treatment with the targeted antibiotics was lower in the intervention (4 [3-7] days per patient) than in the control group (6 [4-10] days per patient; p = 0.002). Differences in number of days on treatment only reached statistical significance in the prescriptions of carbapenems. There were no differences between intervention and control groups in terms of number of deaths, hospital readmissions, length of hospital stay, or antibiotic costs. In this trial, an intervention without restrictions focussed on antimicrobial prescriptions of commonly used antibiotics in the hospital setting had a limited efficacy to reduce consumption and did not save costs. Future strategies to promote a more rational antimicrobial use should be evaluated with a randomized controlled design.

Critical steps in fluoroquinolones and carbapenems prescriptions: results from a prospective clinical audit

Antibiotic misuse is associated with emergence of resistance and high expenditures. Fluoroquinolones (FQ) and carbapenems (CP) are drugs with considerable potential of resistance development and its disseminated use is a concern. We undertook a prospective clinical audit to evaluate prescriptions of FQ and CP in a multistep process. Each prescription was unfolded in the following steps: indication for antimicrobial therapy; adequacy of initial prescription, dosage and route; previous cultures; and parenteral-oral transition. There was no antibiotics indication in 8.9% of FQ and 1.5% of CP group (p = 0.07). In CP 25.8% of initial schemes were inappropriate (21% in FQ). Lack of switch to oral therapy comprised 25% of monthly costs of FQ. Inadequacy in initial choice accounted for 13.6% of CP expenses. We concluded that, in spite of infection control restrictive policies, inappropriateness of antibiotic usage is worrisome. Clinical audit in a multistep approach may identify possible flaws in this process.

Nosocomial Infections Caused by Acinetobacter baumannii A Major Threat Worldwide

From the Unite des Rickettsies, Faculte de Medecine, Universite de la Mediterranee, Marseille, France (both authors). Received May 15, 2006; accepted May 15, 2006; electronically published June 23, 2006. Infect Control Hosp Epidemiol 2006; 27:645-646 2006 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2006/2707-0001$15.00. Currently, Acinetobacter baumannii is considered to be an important and emerging hospital-acquired pathogen worldwide. It is responsible for 2%-10% of all gram-negative bacterial infections in intensive care units in Europe and the United States. However, despite the importance of this organism as a public health problem, several shadow areas persist regarding its virulence, antimicrobial resistance, reservoirs, and epidemiology. Several articles published in this issue of ICHE shed some light on this fascinating bacterium. Some of the uncertainties surrounding A. baumannii are related to the fact that bacteria classified as members of the genus Acinetobacter have a long history of taxonomic changes, moving from the family Neisseriaceae to the family Moraxellaceae. Within the genus Acinetobacter, studies based on DNA-DNA hybridization have described 25 “genomic species” that fulfilled the criteria to be considered as distinct species, and 17 of these have officially been validated to date. This situation has led contributors to the Manual of Clinical Microbiology to state that the majority of the genomic species cannot be reliably distinguished by phenotypic tests. Despite that, and because of the difficulties in differentiating the isolates according to their phenotypic characteristics, the term Acinetobacter calcoaceticus–Acinetobacter baumannii complex is often used. It is important to note, and this may be a limitation of the studies we comment on in this editorial, that in 3 of the 4 studies, species identification was performed using phenotypic methods only, and the isolates were named either A. baumannii or A. baumannii-calcoaceticus. In the study in this issue of the journal by Griffith et al., ribotyping, which could have been used to identify the isolates, was used to compare the isolates but not to identify them, and the isolates were also classified as A. baumanniicalcoaceticus. One of the main concerns about A. baumannii is a characteristic that makes it a major threat to public health, namely, its remarkable ability to rapidly develop antibiotic resistance, mostly by acquisition of gene clusters carried by plasmids, transposons, or integrons, sometimes arranged in resistance islands within the genome. This phenomenon led to multidrug resistance in this species within a few decades. With the emergence of increasingly resistant strains, the management of A. baumannii infection has become a public health problem in many countries. To date, some strains of A. baumannii have become resistant to almost all currently available antibacterial agents, including carbapenems, which were once considered the drug of choice for treatment of A. baumannii infection. In this issue, Peleg et al. describe the frightening emergence of carbapenem resistance in A. baumannii isolates over a 3-year period in an Australian hospital, significantly linked to an increased used of meropenem. They demonstrated, by pulsed-field gel electrophoresis, the clonal origin of these multidrug-resistant strains, but they failed to identify the mechanism associated with carbapenem resistance. The latter point is of particular interest, because Peleg et al. screened strains for the presence of the genes for carbapenemhydrolyzing b-lactamases most commonly found in other countries. However, although Peleg et al. suggested that there may be a nonenzymatic mechanism of resistance or a new b-lactamase, they did not search all currently described genes coding for carbapenem-hydrolyzing b-lactamases. The identification of the mechanism involved in carbapenem resistance in this clonal population of A. baumannii should warrant further investigation to determine whether the bacterium has acquired a resistance gene that is spreading around the world or a gene “made in Australia.” Finally, this article by Peleg et al. emphasizes the risk of misuse of antibiotics, because of the extremely rapid emergence of antibiotic resistance in A. baumannii, and the consequent need for strict rules for prescription of carbapenems. In addition to its propensity to acquire antibiotic resistance, A. baumannii is feared for its ability to cause outbreaks of disease in healthcare facilities. Such outbreaks may take particular forms, such as those that involve multiple facilities. In France, the AYE strain, which produces an extended-spectrum b-lactamase, spread throughout 54 healthcare facilities in 8 administrative regions during an 11-month period. In their study, Fillaux et al. used pulsed-field gel electrophoresis to compare 1,277 A. baumannii strains, including 148 mul-

Nosocomial outbreak of ampicillin resistant Enterococcus faecium: Risk factors for infection and fatal outcome

A nosocomial outbreak caused by ampicillin resistant Enterococcus faecium (ARE) was detected at a Norwegian university hospital in January 1995. Prior to this outbreak, ARE were not common in this hospital or other hospitals in Norway. During 1995 and 1996, a total of 149 cases with clinical ARE infection were detected prospectively. A case control study was performed by allocating controls matched for gender, age and ward of admission. Altogether, 123 case control pairs with mean age 70.1 years were included. Isolates from 89 (72.4%) of the cases were identical or related to the defined outbreak strain as determined by pulsed-field gel electrophoresis (PFGE). In 75 of the patients (60.9%), ARE caused urinary tract infection, five (4.1%) had bacteraemia, 33 (26.8%) had wound infection and 10 (8.1%) had other infections. In a logistic regression model for 1:1 matched samples, the following factors were identified as significant risk factors for ARE infection: underlying neurological disease (OR=33.5), prescription of antimicrobial agents for more than 10 days (OR=8.99), prescription of cephalosporins (OR=4.69), underlying gastrointestinal disease (OR=3.36) and length of hospital stay per day (OR=1.04). The intrahospital death rate for the cases was 18.7% compared with 8.9% for the controls, corresponding to an excess mortality attributable to ARE infection of 9.8%. A history of carbapenem prescription was the only independent factor contributing to death (OR=5.64) when comparing ARE patients dying in hospital to those surviving.