Journal of Antimicrobial Chemotherapy (1999) 43, 423-424
© 1999 The British Society for Antimicrobial Chemotherapy
Correspondence |
The effect of the inoculum size on bactericidal activity
J Antimicrob Chemother 1999; 43: 423– 424
GR Micro Ltd, 7–9 William Road, London NW1 3ER,UK
Sir,
In a recent issue, König et al. 1 described the effect of the inoculum size on the activities of various antibiotics against Escherichia coli and Staphylococcus aureus. They showed that the activity of ciprofloxacin, expressed in terms of the MIC, was notmarkedly affected by this parameter. We wish, firstly, to point out that Chin & Neu 2 demonstrated 15 years ago that the inoculum size does not affect the MICs of thefluoroquinolones.
König et al. 1 also concluded that the bactericidal activity of ciprofloxacin, in terms of the MBC, was equally unaffected by the inoculum size. However, these investigators neglected to compare theirresults with other published data. For example, it had been shown previously that the bactericidalactivities of ofloxacin and ciprofloxacin against E. coli and S. aureus are reduced when the initial inoculum size is increased from 10 9 cfu/L to 10 11 cfu/L and are totally eliminated when inocula of c.10 13 cfu/L are used. 3 This inoculum effect has been attributed to a greatly reduced oxygen tension at high bacterialdensities. 4 Therefore, in contrast to the results of König et al., there are data showing that the bactericidal activities of the fluoroquinolones are indeedinfluenced by the inoculum size. In further support of this contention, we provide here newinformation about the inoculum effect exhibited by fluoroquinolones and cefotaxime in relationto Streptococcus pneumoniae.
The bactericidal activities of levofloxacin, ofloxacin, cefotaxime (Hoechst Marion Roussel,Romainville, France), sparfloxacin (Rhône-Poulenc Rorer, Vitry sur Seine, France), andciprofloxacin (Bayer, Newbury, UK) against S. pneumoniae C3LN4 were determined by a broth dilution method. The bacterium was inoculated into nutrientbroth No. 2 (Unipath, Basingstoke, UK) supplemented with 7% (v/v) laked horse blood (Unipath) containing each drug at a concentration that reflected its potential maximumbactericidal activity (see the Table for concentrations); the fluoroquinolones were therefore testedat their respective optimum bactericidal concentrations (OBCs) 5 and cefotaxime was tested at a concentration equivalent to the mean peak serum concentrationfollowing a single 1 g iv dose. 6 The inocula, which were prepared as described previously, 3 ranged from 10 8 to 10 13 cfu/L. The suspensions were incubated at 37°C for 3 h, after which 100 µL aliquots were withdrawn and inoculated on to nutrient agar No. 2 (Unipath) supplemented with7% laked horse blood. After overnight incubation, the colonies were counted and the numbers ofviable bacteria in the suspensions were calculated.
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The percentages of S. pneumoniae C3LN4, at initial inoculum sizes of 10 9, 10 11 and 10 13 cfu/L, that survived after incubation for 3 h in the presence of the various antibiotics are shown in theTable. The bactericidal activities of levofloxacin and ofloxacin at inocula of 10 9 cfu/L were greater than those of ciprofloxacin and sparfloxacin, an observation in accord withour previous findings. 5 When the initial inocula were increased to 10 11 cfu/L, the bactericidal activities of all the fluoroquinolones tested were reduced markedly, and at10 13 cfu/L the activities were effectively bacteriostatic. These results agree with those alreadyreported for ciprofloxacin and ofloxacin against E. coli and S. aureus. 3 In contrast, increasing the inoculum size had no effect on the bactericidal activity of cefotaxime.It might be argued that, had the fluoroquinolones been tested at concentrations as high as that ofcefotaxime, an inoculum effect with the former group of drugs would not have been observed.However, earlier data demonstrated an inoculum effect with the quinolones when they were usedat concentrations as high as 500 mg/L. 3
The results of the present study are in accord with those of König et al. in demonstrating that an inoculum effect varies from drug class to drug class. 1 However, in contrast to their findings, we have shown that the bactericidal activities offluoroquinolones such as levofloxacin, ciprofloxacin, ofloxacin, and sparfloxacin are markedlyaffected by the inoculum size. This difference can probably be accounted for by variations inmethodology, König et al. having used the MBC as a measure of the bactericidal activity of the quinolones, whereas weused the OBC. Further studies designed to determine whether novel fluoroquinolones alsoexhibit an inoculum effect are warranted, particularly if these drugs are to be used in clinicalsettings in which the numbers of bacteria at the sites of infections are veryhigh.
Notes
* Corresponding author. Tel: +44-171-388 7320; Fax: +44-171-388-7324. 
References
1
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König, C., Simmen, H.-P. & Blaser, J. (1998). Bacterial concentrations in
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2
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Chin, N. X. & Neu, H. C. (1983). In-vitro
activity of enoxacin, a quinolone carboxylic acid,compared to those of norfloxacin, new ß
-lactams, aminoglycosides and trimethoprim. Antimicrobial Agents and
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3 . Morrissey, I., Lewin, C. S. & Smith, J. T. (1990). The influence of oxygen upon bactericidalpotency. In The 4-Quinolones: Antibacterial Agents in Vitro (Crumplin, G. C., Ed.), pp. 23–36. Springer-Verlag,London.
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George, J. & Morrissey, I. (1997). The bactericidal activity of levofloxacin
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(1983).Comparative pharmacokinetics of cefoperazone, cefotaxime, and
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