Faculty Bibliography

OBJECTIVES/OBJECTIVE:Carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa are endemic in many medical centres. Because therapeutic options are limited, understanding the epidemiology and controlling the spread of these pathogens are of paramount importance. METHODS:Isolates of K. pneumoniae, A. baumannii and P. aeruginosa were collected from 14 hospitals in New York City over a 3 month period in 2009, and analysed for the presence of genes encoding important carbapenemases. Comparisons were made with a similar study conducted in 2006. Demographic and infection control-related information from hospitals was collected. RESULTS:Overall, 29% of K. pneumoniae possessed the carbapenemase KPC, significantly improved from the 38% observed in 2006 (P < 0.001). However, carbapenem resistance worsened in A. baumannii (mostly due to the emergence of strains with OXA-type carbapenemases) and P. aeruginosa. The decline in KPC-possessing K. pneumoniae was not uniformly observed in all of the hospitals. In a subset analysis of nine hospitals, those with a decreasing prevalence of bla(KPC) had shorter average lengths of stay. CONCLUSIONS:Measurable improvement has occurred in reducing the spread of KPC-possessing K. pneumoniae, and reducing the average length of stay may augment infection control efforts. However, the problem of carbapenem-resistant A. baumannii and P. aeruginosa lingers. New approaches, including respiratory isolation and environmental cleaning, need to be examined to control the spread of A. baumannii and P. aeruginosa.

Multidrug-resistant Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa have become common in many regions, often requiring therapy with colistin or polymyxin B. An increase in resistance to these agents would render many infections untreatable. We tested the activity of polymyxin B and the novel polymyxin analogue CB-182,804 against over 5,000 recent Gram-negative clinical isolates from New York City, a region with a high prevalence of multiresistant strains. Over 96% of Escherichia coli, K. pneumoniae, A. baumannii, and P. aeruginosa were susceptible to polymyxin B; only 76% of Enterobacter spp. was susceptible. The MICs of CB-182,804 were generally two-fold higher than polymyxin B and cross-resistance was observed. The addition of rifampin resulted in synergistic inhibition and bactericidal activity in time kill studies, and restored activity against all polymyxin-resistant strains. The synergistic effect of the combination with rifampin was most pronounced against A. baumannii strains, and was slightly greater with CB-182,804 than with polymyxin B against K. pneumoniae and Enterobacter spp. Despite considerable usage of polymyxin B and colistin in this region, polymyxin B retains excellent activity against most Gram-negative isolates. CB-182,804 shows similar activity, particularly when combined with rifampin. The clinical utility of CB-182,804 remains to be determined.

We report the first case of recurrent intravascular-catheter-related bacteremia in a pediatric hemodialysis patient caused by Delftia acidovorans, previously called Comamonas acidovorans or Pseudomonas acidovorans. The patient had a history of multiple infections of central vascular catheters with other organisms, requiring courses of antibiotics and catheter replacements. Previously reported cases of D. acidovorans infections are reviewed. The isolate appeared to become resistant to cephalosporins after antibiotic treatment, but resistance could not be confirmed with additional testing. In vitro susceptibility testing for cephalosporins is not reliable for this organism.

OBJECTIVES/OBJECTIVE:Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa have become a global problem, often leaving the polymyxins as therapeutic agents of last resort. ACHN-490, a next-generation aminoglycoside with activity against a broad range of Gram-positive and Gram-negative pathogens, was examined against clinical isolates of A. baumannii and P. aeruginosa. METHODS:The activity of aminoglycosides and ACHN-490 was determined against a contemporary collection of A. baumannii and P. aeruginosa. Selected aminoglycoside-resistant isolates were screened for the presence of genes encoding common aminoglycoside-modifying enzymes and methylases. RESULTS:Resistance to the traditional aminoglycosides was common in the collection of A. baumannii. ACHN-490 possessed superior activity against these isolates, with an MIC(50) value of 8 mg/L. In P. aeruginosa, the activity of ACHN-490 was similar to that of amikacin (MIC(50) value of 8 mg/L for both agents). For both A. baumannii and P. aeruginosa, the MICs of ACHN-490 did not correlate with the presence of commonly encountered aminoglycoside-modifying enzymes. CONCLUSIONS:For A. baumannii, the MICs of ACHN-490 were lower than those of traditional aminoglycosides. For P. aeruginosa, the activity of ACHN-490 was similar to that of amikacin.

The detection of Enterobacteriaceae carrying the carbapenemase KPC has been problematic. Thirty isolates of KPC-possessing Escherichia coli were gathered from hospitals in New York City and Connecticut. The imipenem, meropenem, doripenem, and ertapenem MIC50 values were 4, 2, 1, and 4 μg/ml, respectively. Over half of the isolates belonged to a single ribotype. Using an ertapenem breakpoint of 0.25 μg/ml would efficiently detect these isolates.

OBJECTIVES/OBJECTIVE:Reports of Enterobacteriaceae resistant to all commonly used antimicrobial agents, including β-lactams, fluoroquinolones and aminoglycosides, are increasing in hospitals worldwide. The activity of ACHN-490, a next-generation aminoglycoside, was examined against clinical isolates of Escherichia coli and Klebsiella pneumoniae from hospitals in New York City, an area where multidrug-resistant organisms are endemic. METHODS:Unique patient isolates of E. coli and K. pneumoniae were gathered from 16 hospitals located in New York City in 2009 and underwent susceptibility testing to aminoglycosides and ACHN-490. Subsets of isolates were characterized by PCR for the presence of genes encoding aminoglycoside-modifying enzymes, ribosomal methylases and KPC-type carbapenemases. RESULTS:Although most isolates of E. coli were susceptible to the aminoglycosides, the MIC(90) values of gentamicin, tobramycin and amikacin were 32, 8 and 4 mg/L, respectively. The MIC(90) of ACHN-490 was 1 mg/L. Multidrug resistance, including resistance to aminoglycosides and the presence of bla(KPC), was much more common in isolates of K. pneumoniae. However, the MIC(90) of ACHN-490 for K. pneumoniae was also 1 mg/L. The MICs of ACHN-490 did not correlate with the presence of commonly recovered aminoglycoside-modifying enzymes. Bactericidal activity was evident in most isolates at concentrations 4× the MIC. CONCLUSIONS:The novel aminoglycoside ACHN-490 retains activity against most isolates of E. coli and K. pneumoniae, including multidrug-resistant strains. Additional studies examining the roles of efflux systems and outer membrane permeability alterations are recommended in isolates with reduced susceptibility to this agent.