A Closer Look At Multidrug-Resistant Organisms And Nosocomial Pathogens
Although ESBLs hydrolyze cephalosporins and monobactams such as aztreonam (Azactam, Bristol-Myers Squibb), they do not generally affect cephamycins such as cefoxitin (Mefoxin, Merck) and cefotetan (Cefotan, AstraZeneca) or carbapenems such as meropenem (Merrem, AstraZeneca), imipenem (Primaxin, Merck) or ertapenem (Invanz, Merck). Some strains may also be hyper-producers of beta-lactamase, limiting the usefulness of beta-lactam/beta lactamase inhibitor compounds. In an age of increasing resistance, it is more important than ever that antibiotic choice be guided by culture results.
According to a study by Jadhav and co-workers, over one-half of the ESBL-producing colonies of E. coli were resistant to ciprofloxacin (Cipro, Bayer), implying resistance to all the currently available fluoroquinolones.9 Treatment options are therefore limited. One may consider carbapenems reasonable therapeutic options although tigecycline (Tygacil, Pfizer) may also prove useful.
A notable challenge to today’s podiatric physician has been that of Acinetobacter. The resistance mechanism of Acinetobacter baumannii has been so efficient that it has extended into the hospital-associated strains of the Enterobacteriaceae family such as Klebsiella, E. coli and Enterobacter.10 With even greater healthcare implications, clinicians have discovered Gram-negative, multidrug-resistant organisms in relatively healthy patients outside hospitals.11 Examples include urinary tract infections caused by E. coli that are resistant to trimethoprim/sulfamethoxazole (Bactrim, Roche) and fluoroquinolones, and produce extended beta-lactamases.11
Key Insights On Klebsiella Pneumoniae Carbapenemases
Another enzyme to note is Klebsiella pneumoniae carbapenemase. Originally isolated in Klebsiella pneumoniae, these organisms confer resistance not only to carbapenems but to penicillin, cephalosporins and monobactams. Although most commonly seen in K. pneumoniae, Klebsiella pneumoniae carbapenemases have also been reported in in K. oxytoca, Citrobacter freundii, Enterobacter spp., Escherichia coli, Salmonella spp., Serratia spp. and P. aeruginosa.11
Treatment options are limited and include tigecycline and colistin. Colistin (also known as polymyxin E) is an interesting antibiotic that has enjoyed a re-emergence in recent years to treat infections caused by Gram-negative organisms. Aminoglycosides, when C&S shows susceptibility, may be adjunct therapies.
Bratu and colleagues studied Klebsiella pneumoniae carbapenemase producing K. pneumoniae in bacteremic patients in New York City.12 Results showed that several of the isolates were not only resistant to carbapenems but were also resistant to colistin. As noted previously in recent literature, colistin has long been heralded as the “last resort” antibiotic therapy for Gram-negative infections.12
What The Literature Reveals About Declining Treatment Options
Traditional antibiotic therapies for Gram-negative bacterial infections have included the carbapenems. However, their effectiveness has been steadily declining.13 Bacterial production of beta-lactamases, a.k.a. carbapenemases, is the driving force behind this. Carbapenemases are enzymes that render the beta-lactam ring (the core of the antibiotic structure) completely incompetent.14 Even more worrisome is the ability to transfer this type of resistance between Gram-negative organisms.
Tigecycline is the first of a novel class of broad-spectrum antibiotics, the glycylcyclines, for the parenteral treatment of adult patients with complicated skin and soft-tissue infections. Of particular importance is the drug’s activity against ESBL- and Klebsiella pneumoniae carbapenemase-producing Gram negatives.2
Physicians are now resorting to drastic measures and re-prescribing previously used antibiotics that fell out of use due to serious adverse events.