. 2015 Jan 20;79(2):195–207. doi: 10.1111/bcp.12310

Table 1.

A description of the pharmacology and clinical utility of colistin, pristinamycin and fosfomycin in haematology patients with mutli-resistant organisms

Antibiotic	Class	Mechanism of action	Formulation Oral bioavailability	Dosing Renal/hepatic adjustment	Clinical utility	Comments regarding treatment of multi-drug resistant (MDR) organisms in haematology patients
Colistin^*	Polymyxin	Not completely understood; believed to interact with LPS on gram-negative membrane	i.v., i.m., inhaled	Loading and maintenance dosing calculations required^†	MDR gram-negatives, including Pseudomonas spp. and Acinetobacter spp.	• Renal adjusted dosing safe in haematology and HSCT patients 104,124.
			NA	Renal adjustment required		• Successful treatment in a matched pair analysis of MDR Pseudomonas aeruginosa; median treatment duration 13 days, resolution of infection in 20/26 (76.9%). Single patient suffered renal failure 105.
			NA	Renal adjustment required		• Case report/series data of successful colistin single agent and combination therapy for allogenic HSCT patients and haematology patients with MDR Pseudomonas spp 107,149.
Pristinamycin	Streptogramin	Inhibit protein synthesis via binding peptidyl transferase of 50S subunit of 70S ribosomes	Oral Excellent	500 mg⁻¹ to 1 g TDS No adjustment required	Resistant gram-positive cocci (streptococci, staphylococci > enterococci)	• Limited data specific to haematology cohorts. Majority of data for suppressive therapy for resistant CoNS, MRSA or VRE bone and joint infections 150,151.
Pristinamycin	Streptogramin		Oral Excellent	500 mg⁻¹ to 1 g TDS No adjustment required		• In a retrospective review of 46 cases predominately suppression of VRE or staphylococci (58%) joint, bone or wound infections 152.
Fosfomycin	Phosphoenolpyruvate analogue	Bacterial cell wall inhibition by binding to and inactivating enzyme enolpyruvate transferase	Oral or i.v.	• 3 g single dose (simple UTI)	MDR gram-negatives (except Pseudomonas) and gram-positive cocci (S. aureus and Enterococcus spp. except E. faecalis)	• No specific data for use in haematology patients. Usual clinical indication is gram-negative UTIs, soft tissue infections and surgical prophylaxis 153,154.
			Oral or i.v.	• 3 g alternate days (complicated UTI)		• Primarily for MDR gram-negative UTI, not bacteraemia (E.coli, Citrobacter, Proteus mirabilis including ESBL, however excluding Enterobacter spp., P. vulgaris, Providencia spp., Acinetobacter spp., Pseudomonas spp., Morganella morganii) 153.
			Good^‡ (excellent urinary levels)	• 8 g BD i.v. Renal adjustment if CL_cr <50 ml min⁻¹		• In vitro and in vivo synergy with carbapenems, colistin, fluoroquinolones and tigecycline in 30–74% of gram-positive and gram-negative organisms 155,156.
			Good^‡ (excellent urinary levels)	• 8 g BD i.v. Renal adjustment if CL_cr <50 ml min⁻¹		• Successful mono or combination therapy for suppression of chronic MDR gram-positive infections (e.g. Staphylococcus aureus, Enterococcus spp.) 153

Adapted from Kucers'. The use of Antibiotics (6th edition) – For ‘Class’, ‘Mechanism of action’, ‘Bioavailability’, ‘Dosing’ sections 124. *Colistin is commercially available in two forms: colistin sulphate (referred to in this publication as colistin) and sodium colistin methanesulphonate (CMS). CMS is ‘less toxic’ when administered intravenously and is present in all parenteral (and most inhaled) formulations. CMS undergoes conversion in vivo to form a mixture of partially sulphonmethylated byproducts and colistin 157. †Colistin dosing dependent upon organism MIC and patient renal function. Loading dose of CBA (colistin based activity)(mg) = Colistin organism minimum inhibitory concentration (mg l⁻¹) × 2 × body weight (kg) (use lower of ideal or actual body weight). Maintenance dose of CBA (mg) = Colistin organism minimum inhibitory concentration (mg l⁻¹) × (1.50 × CL_cr + 30) 158. ‡Bioavailability: 37–42%. Oral formulation has high levels in urine for 1–3 days post single dose (1053–4415 mg ml⁻¹). BD, twice daily; CoNS, Coagulase-negative Staphylococcus; CL_cr, creatinine clearance; ESBL, Extended-spectrum-beta-lactamase; HSCT, haematopoietic stem cell transplantation; i.m., intramuscular; i.v., intravenous; LPS, lipopolysaccharide; MDR, multidrug-resistant; MIC, minimum inhibitory concentration.; MRSA, methicillin-resistant Staphylococcus aureus; NA, not applicable; TDS, three times daily; UTI, urinary tract infection; VRE, vancomycin-resistant enterococcus.