Table 2.
Recent studies on inoculum size effect of antibiotics.
| Bacteria | Inoculum size | MIC Change | References |
|---|---|---|---|
| E. coli ATCC 25922 (non-ESBL producer) E. coli Ec1062 (CTX-M-14 producer) | 105.5 CFU/g and 107.5 CFU/g | In an experimental murine sepsis model, piperacillin-tazobactam and imipenem reduced spleen ATCC 25922 strain concentrations (−2.53 and −2.14 log10 CFU/g [P <0.05, respectively]) in the HI vs. LI groups, while amoxicillin-clavulanate maintained its efficacy (−1.01 log10 CFU/g [no statistically significant difference]). Regarding the Ec1062 strain, the antimicrobials showed lower efficacy in the HI than in the LI groups: −0.73, −1.89, and −1.62 log10 CFU/g (P <0.05, for piperacillin-tazobactam, imipenem, and amoxicillin-clavulanate, respectively, although imipenem and amoxicillin-clavulanate were more efficacious than piperacillin-tazobactam). | Docobo-Perez et al., 2013 |
| E. coli | 5 × 102 to 5 × 108 CFU/ml | The concentrations of marbofloxacin needed to eradicate all bacterial population increased from 1- or 2-fold the MIC for low inocula to 128- or 256-fold the MIC for the 5 × 107 and 5 × 108 CFU/ml inocula. | Ferran et al., 2014 |
| MSSA & MRSA | 2.5–4 × 102 to 2.5–4 × 106 CFU/spot | To MSSA, a big IE for ampicillin; small IE for cefazolin, meropenem, and ciprofloxacin; middle IE for teicoplanin and linezolid. | Miyake et al., 2011 |
| To MRSA, small change in vancomycin and arbekacin; middle change in teicoplanin and linezolid. | |||
| MRSA | 104, 106, and 108 CFU/ml | A small IE for vancomycin (MICL = 1 mg/ml, MICM = 1–2 mg/ml, and MICH = 2 mg/ml); a significant IE for daptomycin (MICL = 0.25 mg/ml, MICM = 0.25–0.5 mg/ml, and MICH = 2 mg/ml); no IE for linezolid at low and medium inocula (MICL = 1 mg/ml and MICM = 1–2 mg/ml), but with the high inoculum, concentrations up to 2,048 mg/ml did not fully inhibit visual growth. | Rio-Marques et al., 2014 |
| Staphylococcus aureus Pseudomonas aeruginosa | 105–108 cfu/mL | 105~108 cfu/mL had no significant effect on the MICs of fluoroquinolones and carbapenems; however, inoculum size to >108 cfu/mL resulted in a reduction in bactericidal activity against S. aureus; increasing the inoculum size of P. aeruginosa exerted only a minimal influence on the bactericidal activity of fluoroquinolones, but resulted in a reduction in the bactericidal activity of carbapenems; when the inoculum was increased above 106 cfu/mL, the duration of the PAEs of these antimicrobial agents was reduced; Inoculum size had a greater influence on the in vivo efficacy of carbapenems than that of fluoroquinolones in mouse model. | Mizunaga et al., 2005 |
| P. aeruginosa | 106, 108, and 109 CFU/ml | The killing of the susceptible population was 23-fold slower at the 109 CFU/ml and 6-fold slower at the 108 CFU/ml than at the 106 CFU/ml. | Bulitta et al., 2010 |
| Staphylococus spp Streptococcus spp. Enterobacteriaceae P. aeruginosa | 5 × 103, 5 × 105, and 5 × 107 CFU/ml | An increase over 7-fold of the MIC in ozenoxacin, ciprofloxacin, and levofloxaci at 107 CFU/mL | Tato et al., 2014 |
| Pasteurellaceae | 5 × 105 and 5 × 108 CFU/ml | Marbofloxacin was equally potent against 105 CFU/mL inocula Mannheimia haemolytica and Pasteurella multocida; an IE was observed with P. multocida at a 108 CFU/mL inoculum; no IE was observed with M. haemolytica. At the same dose, the clinical and bacteriological outcomes were much better for mice infected with M. haemolytica than for those infected with P. multocida with 109 CFU of each bacteria | Lhermie et al., 2015 |
| Klebsiella pneumoniae | 105 CFU or 109 CFU/animal | The dose of 50 mg/kg b.w. cefquinome targeting the high K. pneumoniae inoculum cured all the treated rats and resulted in a massive amplification of CTX-M-producing Enterobacteriaceae. A dose of 5 mg/kg targeting the low K. pneumoniae inoculum cured all the rats and averted an outbreak of clinical disease, all without any amplification of CTX-M-producing Enterobacteriaceae. | Vasseur et al., 2014 |
ESBL, extended-spectrum β-lactamase; MSSA, methicillin-susceptible Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus; IE, inoculum effect.