Variables in demonstrating methicillin tolerance in Staphylococcus aureus strains

Ishida, Kouichi; Guze, Phyllis A.; Kalmanson, George M.; Albrandt, Keith; Guze, Lucien B.

doi:10.1128/aac.21.4.688

Cited by 51 publications

(36 citation statements)

References 18 publications

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“…While the growth phase may not have a significant effect on MIC tests, as demonstrated by Barry et al (7) and Kim and Anthony (56), most investigators (48,56,70,75,108,114) have confirmed the importance of using log-phase growth for the inoculum for MBC tests. When stationary-phase growth is used, the number of surviving or "persisting" organisms tends to increase after 24 h of incubation, and therefore the MBC result may be artificially high.…”

Section: Introduction Introductionmentioning

confidence: 86%

“…As noted earlier, Taylor et al (108) demonstrated that early agitation was helpful only with a large initial inoculum volume of 1.0 ml, and not when <0.1 ml was used. Early agitation may remove viable bacterial cells from continued exposure to the antimicrobial agent (48,108). A sample size of 0.1 ml for the subculture gives sufficient precision to the endpoint determination used in the evaluation of the MBC result.…”

Section: Proposed Mbc Test Proceduresmentioning

confidence: 99%

“…They found that gentle agitation at 20 h was useful when a large-volume inoculum (1.0 ml) was used; however, it was not needed when the recommended <0.1-ml inoculum volume was used (108). We (41) (4,8,48,95). The proposed standard recommends a subculture volume of 0.01 ml for macrodilution and 0.01 to 0.1 ml for microdilution tests (75).…”

Section: Introduction Introductionmentioning

confidence: 99%

“…The appearance of bacteriostatic or bactericidal activity is typically determined for each tube in the set, with the result indicating the optimal concentrations of each drug in combination for inhibitory and bactericidal effects. IN (59,67,78,85,99,104,114,120), the use of cation supplements (41,92,107,120), whether the culture is mixed or otherwise agitated during incubation (48,104,105,108,120), the growth phase of the inoculum (7,39,48,57,70,104,105,108,114,120), the pH of the medium (34,105,114,120), the use of serum (binding) proteins (92,120), the presence of complement (21,34,120), the elimination of antibiotic carryover during subculture (8,25,35,47,93,103,104,119,122), the final density of the bacterial inoculum …”

Section: Introduction Introductionmentioning

confidence: 99%

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Tests for bactericidal effects of antimicrobial agents: technical performance and clinical relevance

1992

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Bactericidal testing has been used for several decades as a guide for antimicrobial therapy of serious infections. Such testing is most frequently performed when bactericidal antimicrobial agent therapy is considered necessary (such as when treating infectious endocarditis or infection in an immunocompromised host). It has also been used to ensure that the infecting organism is killed by (not tolerant to) usually bactericidal compounds. However, few data are available to support the role of such tests in direct patient care. Several important variables affect the reproducibility of the test results; however, proposed reference methods are now available for performing the MBC test. With minor modifications, these can provide a standardized approach for laboratories that need to perform them. Currently, little evidence is available to support the routine use of such testing for the care of individual patients. However, testing of new (investigational) antimicrobial agents can be beneficial in determining their potential to provide bactericidal antimicrobial activity during clinical use. New methods to assess bactericidal activity are being developed, but as yet none have been rigorously tested in patient care settings; further, for most of these methods, little information is available as to which technical parameters affect their results. In clinical laboratories, all bactericidal tests must be performed with rigorously standardized techniques and adequate controls, bearing in mind the limitations of the currently available test procedures.

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Section: Introduction Introductionmentioning

confidence: 86%

Section: Proposed Mbc Test Proceduresmentioning

confidence: 99%

Section: Introduction Introductionmentioning

confidence: 99%

Section: Introduction Introductionmentioning

confidence: 99%

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Tests for bactericidal effects of antimicrobial agents: technical performance and clinical relevance

1992

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“…The drug carryover phenomenon has been described for several antibiotics, e.g., ␤-lactams, fluoroquinolones, and clofazimine, and also for antiseptics, such as betadine, chlorhexidine, and niacinamide (2,3,4,7,9). Some methods that can be used to overcome this phenomenon are available, but none of them can be universally applied.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Drug Carryover Effects in Studies Assessing Antimycobacterial Efficacy of TMC207

Lounis¹,

Gevers²,

Berg³

et al. 2008

J Clin Microbiol

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The levels of TMC207 (R207910) that can be reached in mouse organs and the sputa of treated patients easily exceed the MIC of the compound and can therefore interfere with in vitro bacterial titrations. We studied the usefulness of protein-enriched media for the prevention of such drug carryover effects. The average MIC of Mycobacterium tuberculosis was determined on three different media: unsupplemented 7H11 agar (MIC ‫؍‬ 0.03 g/ml), 7H11 agar supplemented with 5% bovine serum albumin (BSA; MIC ‫؍‬ 1 g/ml), and LowensteinJensen medium (MIC ‫؍‬ 14.33 g/ml). In a second stage of the study, the maximal noninhibitory concentrations (MNICs) of TMC207 were determined by adding TMC207 to the bacterial inoculum rather than to the culture medium. These MNICs were 0.97 g/ml for 7H11 agar, 32.33 g/ml for 7H11 agar with 5% BSA, and 96.33 g/ml for Lowenstein-Jensen medium. Both protein-enriched media were able to prevent drug carryover effects, but the use of 7H11 medium supplemented with 5% BSA is preferred for practical reasons.The drug carryover phenomenon can be defined as the inhibition of bacterial growth in vitro which is not due to the inhibition of growth in vivo but, rather, to the presence of high inhibitor concentrations in the tested samples. Failure to recognize the contribution of drug carryover may result in overestimation of a drug's in vivo efficacy. Antibiotics combining high levels of tissue penetration (high volumes of distribution) with low MICs, such as the diarylquinoline TMC207, the nitrodihydro-imidazo-oxazole OPC-67683, the nitroimidazo-oxazine PA-824, and the pyrrole LL-3858 (8), are at risk of displaying the carryover phenomenon when sputum from treated patients or organs from treated animals are cultivated for the isolation of Mycobacterium tuberculosis.TMC207 (also known as R207910) is being assessed in a phase IIb, placebo-controlled, double-blind, randomized trial for the evaluation of its antibacterial activity in subjects with smear-positive pulmonary infection caused by multidrug-resistant M. tuberculosis. Patients are treated for either 2 or 6 months with TMC207 in combination with a background regimen recommended for use for the treatment of multidrugresistant M. tuberculosis infections (a combination of secondline drugs, such as kanamycin, pyrazinamide, ofloxacin, and ethionamide).Following repeated oral administration of TMC207 to the mouse, rat, and dog, the tissue trough levels in all species are high in the lung, spleen, lymph nodes, and thymus, with an average tissue concentration/plasma concentration ratio above 30 (1). Theoretically, concentrations of 10 to 15 g/ml or higher could be achieved in the sputum after several months of treatment with TMC207, and these concentrations exceed the MIC of TMC207 against M. tuberculosis by Ͼ100-fold.When TMC207 was assessed in vitro by equilibrium dialysis, TMC207 was found to be extensively bound to plasma proteins, resulting in a free fraction in the buffer compartment below the quantification limit of the liquid chromatographytandem mass...

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Susceptibility and tolerance of β-lactamase-producing, methicillin-sensitive strains of Staphylococcus aureus towards seven broad-spectrum penicillins

1983

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The activity of penicillin G, ampicillin, carbenicillin, ticarcillin, azlocillin, mezlocillin and piperacillin against 102 beta-lactamase-producing, methicillin-sensitive strains of Staphylococcus aureus was determined by agar dilution (method A) and broth microdilution (method B) techniques. By NCCLS breakpoint criteria, 4% of the strains were "sensitive" to penicillin and ampicillin, and almost 100% were "sensitive" to the other drugs when method A was used. Results with method B were only significantly lower as far as the cumulative percentage of strains "sensitive" to azlocillin, mezlocillin and piperacillin was concerned (63-71%). Bactericidal effects at "sensitive" levels were observed in 0-2% (penicillin, ampicillin), 31-35% (carbenicillin, ticarcillin) and 10-14% (azlocillin, mezlocillin, piperacillin). While differences in MIC and MBC levels ranged from 0 to 8 dilution steps, tolerance (a greater than 32-fold difference) was seen in at least 9-22% of all strains (depending on the drug tested); experimental limitations, however, excluded a determination of tolerance in all our strains. In a semi-quantitative nitrocefin assay, "strong" beta-lactamase production was correlated to high MIC and/or MBC levels.

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Variables in demonstrating methicillin tolerance in Staphylococcus aureus strains

Cited by 51 publications

References 18 publications

Tests for bactericidal effects of antimicrobial agents: technical performance and clinical relevance

Tests for bactericidal effects of antimicrobial agents: technical performance and clinical relevance

Prevention of Drug Carryover Effects in Studies Assessing Antimycobacterial Efficacy of TMC207

Susceptibility and tolerance of β-lactamase-producing, methicillin-sensitive strains of Staphylococcus aureus towards seven broad-spectrum penicillins

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