Colistin, resistance

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal administration, especially for Pseudomonas aerupinosa mP QXiosis, but also for most other gram-negative organisms, such as those resistant to first-line antibiotics. Nephrotoxicity and various neurotoxicities are common in parenteral, but not in topical, use. Resistance to polymyxins develops slowly, involves mutation and, at least in some bacteria, adaptation, a poorly understood type of resistance that is rapidly lost on transfer to a medium free of polymyxin. Resistance can involve changes in the proteins, the lipopolysaccharides, and lipids of the outer membrane of the cell (52). Polymyxin and colistin show complete cross-resistance. 

To prevent development of resistance and promote synergy, inhaled tobramycin or colistin is usually added to an oral fluoroquinolone for P. aeruginosa coverage.1,3 Methicillin-sensitive S. aureus (MSSA) may be treated with oral amoxiciUin-clavulanic acid, dicloxacillin, first- or second-generation cephalosporins, trimethoprim-sulfamethoxazole, or clindamycin, depending on sensitivity. Likewise, methiciUin-resistant S. aureus (MRSA) may be treated with oral trimethoprim-sulfamethoxazole, clindamycin, minocycline, or linezolid. H. influenzae often produces... 

Nebulized colistin using the IV formulation may be an option in patients with tobramycin-resistant strains or intolerance to inhaled tobramycin. Due to an increased risk of bronchoconstriction after colistin inhalation, patients should pre-treat with albuterol and administer the first doses under medical observation.1,5... 

Treatment should be guided by the local or hospital resistance patterns. Extensive use of a quinolone for selective decontamination will increase the incidence of quinolone-resistant gram-negative pathogens. Alternative regimens for gut decontamination are oral colistin with an oral aminoglycoside such as neomycin. 

The polymyxins are a group of basic peptides active against gram-negative bacteria and include polymyxin and polymyxin E (colistin). Polymyxins act like cationic detergents. They attach to and disrupt bacterial cell membranes. They also bind and inactivate endotoxin. Gram-positive organisms, proteus, and neisseria are resistant. 

Gump WC, Walsh JW. Intrathecal colistin for treatment of highly resistant Pseudomonas ventriculitis. Case report and review of the literature. J Neurosurg. 2005 102 915-917. 

Adams, M., Nickel, G., Bajaksouzian, S., Lavender, H., Murthy, A., Jacobs, M., Bonomo, R. Resistance to colistin in Acinetobacter baumannii associated with mutations in the PmrAB two-component system. Antimicro Agents Chemother 53 (2009) 3628-3634. 

Moskowitz, S.M., Bums, J.L., Nguyen, C.D., Hftiby, N., Ernst, R.K., Miller, S.I. Polymyxin resistance and lipid A structure of Pseudomonas aeruginosa isolated from colistin-treated and colistin-naive cystic fibrosis patients. Pediatr Pulmonol Suppl 20 (2000) 272. 

Resistance to polymyxins. The polymyxins (A, B, C, D, E) are a group of antibiotics obtained from Bacillus polymyxa [145]. Polymyxin E is referred to as colistin. These antibiotics are extremely active against strains of Ps. aeruginosa but have the disadvantage of certain toxicity problems. The action of polymyxin is on the cytoplasmic membrane involving the phopholipid components [65,146]. 

The ototopical antimicrobial preparations stated earlier suffice for most cases of otitis externa and selected cases of chronic suppurative otitis. However, these compounds have a limited effect in certain patients with resistant strains of bacteria, drug-induced allergies, or a tympanic membrane perforation that requires administration into the middle ear space. In the last case, ototopical preparations may cause pain because of the acidic pH or the presence of alcohol. Ototoxicity of neomycin, polymyxin B, and colistin is also of concern, and many otolaryngologists prefer topical ophthalmic preparations.f Ophthalmic preparations are discussed in the article Ocular Drug Formulation and Delivery in this volume. 

Resistance to colistin has been analysed in 44 adults with cystic fibrosis treated with inhaled colistin. Five developed polymyxin resistance (31). After therapy P. aeruginosa became sensitive to polymyxins within a few months, enabling the reintroduction of colistin for antibacterial treatment. 

In a study of the intrathecal administration of colistin adverse events were not reported (36). This may be an effective alternative treatment of bacterial meningitis caused by multidrug-resistant Gram-negative rods. 

Jimenez-Mejias ME, Pichardo-Guerrero C, Marquez-Rivas FJ, Martin-Lozano D, Prados T, Pachon J. Cerebrospinal fluid penetration and pharmacokinetic/phar-macodynamic parameters of intravenously administered colistin in a case of multidrug-resistant Acinetobacter bau-mannii meningitis. Eur J CUn Microbiol Infect Dis 2002 21(3) 212-14. 

Gunderson BW, Ibrahim KH, Hovde LB, et al. Synergistic activity of colistin and ceftazidime against multiantibiotic-resistant Pseudomonas aeruginosa in an in vitto pharmacodynamic model. Antimicrob Agents Chemother 2003 47 905-909. 

In contrast to many other, primarily bacteriostatic drugs, both colistin and polymyxin rarely induce resistance during repeated passage of normally sensitive strains in subinhibitory concentrations. 

Polymyxin B sulfate is available for ophthalmic, otic, and topical use in combination with a variety of other compounds. Colistin is available as otic drops. Parenteral preparations are rarely used, but colistin may be useful as a salvage regimen for infections caused by multiple-drug-resistant organisms. 

Organism exhibits intermediate resistance to colistin concentration (disc) 2 yg. 

A probable hypersensitivity pneumonitis secondary to inhaled aerosolized coUstin has been reported in a 68-year-old Indian woman who was successfully treated for a nosocomial pneumonia due to a multidrug-resistant Acinetobacter baumarmii [100 ]. The authors postulated that the hypersensitivity pneumonitis was due to conversion of the prodrug, colistimethate, to the biologically active form of colistin, which is less well tolerated. They recommended ensuring that the prodrug is only reconstituted just before administration to avoid excessive conversion to the biologically active drug. 

Nervous system Of 7 patients from a Thai hospital and 17 patients who received intrathecal cohstin for drug-resistant Acinetobacter baumannii central nervous system infection identified in a literature review, three developed chemical ventriculitis and one had treatment-emergent seizures [101 ]. The dosage regimens of intrathecal colistin varied. There was an overall clinical cure rate of 83% and a microbiological cure rate of 92%. 

In a single-center prospective comparison of intravenous colistin ( =200) and imipenem, meropenem, or ampicillin/sul-bactam (n=295) the 30-day mortality rates were 39% versus 29% respectively [110. The difference also reached statistical significance in the subgroup of patients with infections caused by Klebsiella pneumoniae (40/104, 39% versus 18/80, 23% OR=2.2 95% Cl = 1.1, 4.2). Treatment with colistin was significantly associated with death (overall adjusted HR =1.3 95% CI = 1.01, 1.6). Renal insufficiency was more frequent among patients treated with colistin (adjusted OR >3). After 3 months follow-up the use of colistin was associated with a higher rate of resistant Proteus species. 

Khawcharoenporn T, Apisamthanarak A, Mundy LM. Intrathecal colistin for drug-resistant Acinetobacter baumannii central nervous system infection a case series and systematic review. Clin Microbiol Infect 2010 16(7) 888-94. 

Baiocchi M, Catena V, Zago S, Badolati L, Baccarin M. Intrathecal colistin for treatment of multidrug resistant (MDR) Pseudomonas aeruginosa after neurosurgical ventriculitis. Infez Med 2010 18(3) 182-6. 

Nikita D, Michalopoulos A. Colistin therapy for microbiologically documented multidrug-resistant Gram-negative bacterial infections a retrospective cohort study of 258 patients. Int J Antimicrob Agents 2010 35(2) 194-9. 

Intravenous and nebulized colistin in the treatment of multidrug resistant Gram-negative infections have been analysed in two retrospective chart reviews of 115 and 121 treatments [177 178 ]. There was nephrotoxicity in 8.3% and 14% respectively, and chronic renal insufficiency, diabetes mellitus, and aminoglycoside use were associated susceptibility factors. Four patients experienced neurotoxicity in one study. 

Montero M, Horcajada JP, Sorlf L, Alva-rez-Lerma F, Grau S, Riu M, Sala M, Knobel H. Effectiveness and safety of colistin for the treatment of multidrug-resistant Pseudomonas aeruginosa infections. Infection 2009 37(5) 461-5. 

A multicenter, observational study investigated the effectiveness and toxicity of colistin in a paediatric intensive care setting. Seventy-nine patients were followed with a median age of 30 months. Four serious adverse events were recorded, including two of each of renal failure and seizures [134 ]. A survey study of 229 paediatric infectious disease specialists gathered data on 92 cases of colistin use in children. Twenty-two percent of children developed nephrotoxicity and four children developed reversible neurotoxicity. Concemingly development of resistance to colistin was noted in 20.5% [135 j. 

A retrospective matched case-control study was carried out to determine the effect of inhaled colistin (160 mg twice daily) in patients with multidrug resistant Acinetobacter baumannii infection. The majority of patients reviewed were intensive care patients with baseline renal impairment. After 28 days of treatment, 17.9% developed haemodynamic instability, 30.6% developed acute renal failure and 20.8% required intubation. These results were not different to the control group and highlight the poor clinical state of the patient rather than the antibiotic used [137 ]. 

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