Antimicrobial activity of borate-buffered solutions

Abstract

A minimal salts medium adjusted to physiological pH and osmolality was buffered with either 0.3% phosphate or 1.2% borate and evaluated for antimicrobial activity. The borate-buffered medium, either with or without a carbon source, exhibited significant antimicrobial activity against 15 Pseudomonas strains, 12 strains of enteric bacteria, and 7 strains of staphylococci. The borate-buffered system appears suitable for use as a generic vehicle for ophthalmic pharmaceutical agents.In 1958, Kingma summarized the pharmacology and toxicology of boron compounds (10 on neonates (5), and by two pharmacokinetic studies of oral (14) and intravenous (9) administration.The present study evaluated the antimicrobial activity of 1.22% borate buffer in a minimal salts medium, with and without a carbon source (glucose). For comparison, phosphate-buffered and unbuffered minimal salts media were also evaluated. The antimicrobial activity of the solutions was evaluated as a function of the log change in viable cell count over 28 days. The significance of the results as they relate to the preservative effectiveness test described by the United States Pharmacopeia (USP XXI) and their application to ophthalmic pharmaceuticals is discussed. MATERIALS AND METHODSMicoorganisms. The microorganisms that were tested are listed in Tables 1 to 4. They were obtained from several different sources, including clinical, environmental, and product isolates.Defined media. Minimal media used with the Pseudomonas strains contained 0.04% (NH4)2SO4 and 0.05% MgSO4, either unbuffered, buffered with 0.10% KH2PO4 7H20 and 0.02% Na2HPO4, or buffered with 1.00% boric acid and 0.22% Na2B407 10H20. The minimal medium for the enteric bacteria and staphylococci contained 0.04% (NH4)2SO4, 0.02% MgSO4 7H2O, 0.02% CaC12 * 2H20, 0.0025% Na,MoO4 2H20, and 1.00% vitamin solution. The vitamin solution was prepared separately at 10Ox concentration and filter sterilized. The final concentrations were 0.0005% calcium pantothenate, 0.0001% thiamine hydrochloride, 0.0001% pyridoxine hydrochloride, 0.0001% biotin, and 0.0001% nicotinic acid. Each solution was made isotonic with 0.9% NaCl by calculating the salt equivalent of each ingredient and adding the appropriate amount of NaCl. The pH of each solution was adjusted to 7.00 ± 0.2 with hydrochloride or KOH. The glucose, MgSO4, CaCl2, and NaMoO4 were autoclaved separately at 10Ox concentration and then aseptically transferred to the minimal media.The microorganisms were transferred from nutrient broth to the defined minimal medium containing phosphate and glucose. After the microorganisms adapted and began growing in the minimal medium, a second 24-h culture was used for each experiment. The respective cultures were harvested by centrifugation, washed three times in distilled water, and standardized at A500 to give approximately 106 CFU/ml.The staphylococci were unable to grow in the minimal medium without the addition of amino acids. They were therefore harvested directly from the tryptic soy broth, washed three times in d...

Adaptation and growth of Serratia marcescens in contact lens disinfectant solutions containing chlorhexidine gluconate

“…Solutions containing borate ions in combination with chlorhexidine effectively inhibited unadapted S. marcescens with linear killing kinetics, whereas cells adapted to phosphate-buffered chlorhexidine showed biphasic killing curves in borate-buffered chlorhexidine. Antimicrobial activity of borate solutions for ophthalmic products has been noted by Houlsby et al (14). Ogunbiyi et al (21) reported that borate ions enhanced the activity of polyhexamethylene biguanides, and Wilson et al (27) noted relatively greater inhibitory activity for several contact lens solutions containing borate versus phosphate buffers.…”

Assessing the Contributions of the LiaS Histidine Kinase to the Innate Resistance of Listeria monocytogenes to Nisin, Cephalosporins, and Disinfectants

“…It was also apparent that the ⌬liaS mutant is more sensitive than LO28 to chloroxylenol, novobiocin, chloramphenicol, iodoacetate, doxycycline, pentachlorophenol, and sodium metaborate (Table 3). Chloroxylenol functions by disrupting the membrane potential of cells and is used in antibacterial soaps as well as being the active ingredient in the household antiseptic Dettol (44), novobiocin inhibits DNA gyrase, pentachlorophenol is used as a wood preservative and, previously, in disinfectant cleaners (46), iodoacetate is an inhibitor of glycolytic pathway enzyme GAPDH (glyceraldehyde-3-phosphate dehydrogenase) (43), and sodium metaborate is used in hard-surface cleaners to remove grease, rust, and scale from metal, glass, and detergents (24). It would thus seem that the status of the LiaSR system in L. monocytogenes impacts differently on the resistance of the pathogen to a variety of disinfectants and industrial hygiene agents.…”

In Vitro Cytotoxicity Screening as a Criterion for the Rational Selection of Tear Substitutes

“…It is not currently clear what phosphate concentration is critical for the onset of corneal calcification. Quite recently, preference has been given to borate buffers, which possess antimicrobial activity, showed good biocompatibility with the ocular surface both in vivo and in vitro and are considered safer [26,27]. Tris buffers are also included in some dosage forms and have been found to be effective and low toxic [28].…”