Drugs of Last Resort? The Use of Polymyxins and Tigecycline at US Veterans Affairs Medical Centers, 2005–2010

Multidrug-resistant (MDR) and carbapenem-resistant (CR) Gram-negative pathogens are becoming increasingly prevalent around the globe. Polymyxins and tigecycline are among the few antibiotics available to treat infections with these bacteria but little is known about the frequency of their use. We therefore aimed to estimate the parenteral use of these two drugs in Veterans Affairs medical centers (VAMCs) and to describe the pathogens associated with their administration. For this purpose we retrospectively analyzed barcode medication administration data of parenteral administrations of polymyxins and tigecycline in 127 acute-care VAMCs between October 2005 and September 2010. Overall, polymyxin and tigecycline use were relatively low at 0.8 days of therapy (DOT)/1000 patient days (PD) and 1.6 DOT/1000PD, respectively. Use varied widely across facilities, but increased overall during the study period. Eight facilities accounted for three-quarters of all polymyxin use. The same statistic for tigecycline use was twenty-six VAMCs. There were 1,081 MDR or CR isolates during 747 hospitalizations associated with polymyxin use (1.4/hospitalization). For tigecycline these number were slightly lower: 671 MDR or CR isolates during 500 hospitalizations (1.3/hospitalization) (p = 0.06). An ecological correlation between the two antibiotics and combined CR and MDR Gram-negative isolates per 1000PD during the study period was also observed (Pearson’s correlation coefficient r = 0.55 polymyxin, r = 0.19 tigecycline). In summary, while polymyxin and tigecycline use is low in most VAMCs, there has been an increase over the study period. Polymyxin use in particular is associated with the presence of MDR Gram-negative pathogens and may be useful as a surveillance measure in the future

Evaluation of uncomplicated acute respiratory tract infection management in veterans: A national utilization review.

BackgroundAntibiotics are overprescribed for acute respiratory tract infections (ARIs). Guidelines provide criteria to determine which patients should receive antibiotics. We assessed congruence between documentation of ARI diagnostic and treatment practices with guideline recommendations, treatment appropriateness, and outcomes.MethodsA multicenter quality improvement evaluation was conducted in 28 Veterans Affairs facilities. We included visits for pharyngitis, rhinosinusitis, bronchitis, and upper respiratory tract infections (URI-NOS) that occurred during the 2015-2016 winter season. A manual record review identified complicated cases, which were excluded. Data were extracted for visits meeting criteria, followed by analysis of practice patterns, guideline congruence, and outcomes.ResultsOf 5,740 visits, 4,305 met our inclusion criteria: pharyngitis (n = 558), rhinosinusitis (n = 715), bronchitis (n = 1,155), URI-NOS (n = 1,475), or mixed diagnoses (>1 ARI diagnosis) (n = 402). Antibiotics were prescribed in 68% of visits: pharyngitis (69%), rhinosinusitis (89%), bronchitis (86%), URI-NOS (37%), and mixed diagnosis (86%). Streptococcal diagnostic testing was performed in 33% of pharyngitis visits; group A Streptococcus was identified in 3% of visits. Streptococcal tests were ordered less frequently for patients who received antibiotics (28%) than those who did not receive antibiotics 44%; P < .01). Although 68% of visits for rhinosinusitis had documentation of symptoms, only 32% met diagnostic criteria for antibiotics. Overall, 39% of patients with uncomplicated ARIs received appropriate antibiotic management. The proportion of 30-day return visits for ARI care was similar for appropriate (11%) or inappropriate (10%) antibiotic management (P = .22).ConclusionsAntibiotics were prescribed in most uncomplicated ARI visits, indicating substantial overuse. Practice was frequently discordant with guideline diagnostic and treatment recommendations

In Vitro Bactericidal Activities of ABT-773 against ermB Strains of Streptococcus pneumoniae

The bactericidal activities of ABT-773, a new ketolide, were compared to those of cefuroxime and amoxicillin-clavulanate against 10 strains of Streptococcus pneumoniae containing the ermB gene. MICs and time-kill curves were determined in duplicate per NCCLS guidelines with cation-adjusted Mueller-Hinton broth with 3% lysed horse blood. Viable counts were done at 0, 2, 6, and 24 h. Antibiotic concentrations tested were two and eight times the MIC. ABT-773 MICs ranged from 0.008 to 1.0 μg/ml. Bactericidal activity was observed with ABT-773 at eight times the MIC against 4 of 10 strains at 24 h compared to 10 of 10 strains with the beta-lactam antibiotics

Initiation and termination of antibiotic regimens in Veterans Affairs hospitals.

ObjectivesTo assess rates of starting or stopping antibiotics across different hospitals.MethodsWe used barcode medication administration data to measure antibiotic use on acute-care wards in 128 Veterans Affairs medical centres (VAMCs) in 2010. A treatment day (TD) was defined as the administration of any antibiotic on a given day. A treatment period (TP) was defined as an interval of inpatient antimicrobial therapy with gaps of ≤1 day in TDs. The rate of starting antibiotics was calculated for inpatients who had not yet started antibiotics, as the number of start events divided by the 'person-time at risk'. The rate of stopping antibiotics was calculated analogously for inpatients that were on antibiotics. Once individuals had stopped antibiotics they were removed from further analysis. Per-day start and stop rates were also calculated for each day of hospitalization.ResultsThe hospital mean rate of starting the first TP was 18.1 start events/100 days at risk (range 8.4-25.6/100 days at risk). The mean hospital stopping rate was 21.1 stop events/100 days at risk (range 13.3-29.5/100 days at risk). The ratio of a facility's starting and stopping rates was highly correlated with overall antibiotic use in TDs/1000 patient-days (rs=0.92, P<0.001), while starting and stopping rates individually were only moderately correlated (rs=0.39, P<0.001).ConclusionsVAMCs with similar antibiotic use showed marked differences in their starting and stopping rates of antibiotics. It may be useful to target empirical therapy when starting rates are high and definitive therapy when stopping rates are low

Trends in the use of polymyxin and tigecycline in days of therapy (DOT) per 1000 patient days (PD) by fiscal year.

<p>Trends in the use of polymyxin and tigecycline in days of therapy (DOT) per 1000 patient days (PD) by fiscal year.</p

Dot plot of tigecycline and polymyxin use by facility in DOT per 1000 PD in fiscal year 2010. Each dot represents one facility (n = 127).

<p>Dot plot of tigecycline and polymyxin use by facility in DOT per 1000 PD in fiscal year 2010. Each dot represents one facility (n = 127).</p

Pathogens isolated.

<p>a) when polymyxins (1,145 hospitalizations) or b) tigecycline (3,125 hospitalizations) were used. Only <i>Acinetobacter spp.</i>, <i>E. coli</i>, <i>Klebsiella spp.</i> and <i>P. aeruginosa*</i> are included <b>MDR:</b> multi-drug resistance (non-susceptibility to > = 3 drug classes) <b>CR:</b> carbapenem resistance (non-susceptibility to carbapenems; ertapenem not considered for non-fermenters) <b>XDR:</b> non-susceptibility to all tested classes except to polymyxins (definitions of MDR, CR and XDR adapted from reference <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036649#pone.0036649-Magiorakos1" target="_blank">[22]</a>) *In 206/225 cases where tigecycline was given and a Pseudomonas was isolated, the patient had at least one anti-pseudomonal spectrum agent (definition of anti-pseudomonal activity based on reference <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036649#pone.0036649-Magiorakos1" target="_blank">[22]</a>).</p