Susceptibility of the Micro-organisms to Inoculum

About the Study

The number of organisms at the infected area may affect the antibacterial action that is seen at any given medication solution. As a result, the inoculum's thickness may be a key factor in determining a drug's effectiveness. Early studies unmistakably showed that a substantial determinant of functional recovery is the length of the disease prior to therapy. The effectiveness of that therapy is frequently effected by delays in treatment, which could theoretically result in a bigger inoculum. In non-neutropenic rats, greater medication doses were required to treat Microbial strains when the sickness was allowed to continue for 34 hours as opposed to five hours, whether the antibiotic was given continuously or intermittently. Numerous theories have been put out to explain this incident. Large inocula may provide a higher local density of enzymes that efficiently lower antibiotic concentrations at the infection site by making them functional rather than active.

Additionally, due to the selective impact of the antibiotics, large bacterial populations are significantly more likely to have resistant species that develop through spontaneous mutation and prevail both in the population. One such instance was seen in a murine model of group A streptococcal myositis, where the existence of a large inoculum (10⁸ × 10⁹ CFUs/mL) greatly impairs the action of penicillin while having just a minimal effect on the function of clindamycin. This effect of the inoculum was attributed in part to the selection of a cell wall-deficient mutant, which is acceptable provided that the isolate didn't produce -lactamase and that any leftover PAE was unrelated because both medications kept drug levels above the MIC for the period of the test period.

Although not all organisms are susceptible to the inoculum effect, 215 clindamycin does have some vulnerability to it. In a murine Bacillus fragilis abscess model, a smaller reduction in log10CFUs was seen when the inoculum size was increased or the delay until medication was given. A further theory for how the inoculum works is based on the observation that organisms in dense groups may develop more slowly or become metabolically inactive than those in less dense populations. Antibiotic drugs that are bactericidal against both fast developing and fixed organisms are unlikely to be impacted by this procedure (e.g., fluoroquinolones). Consequently, in the combination of an established infection where the number of microorganisms is large and up to 90% of the organisms may be slowly dividing and, therefore, biologically inactive, activity for agents that exert their bactericidal effects primarily on rapidly dividing organisms (e.g., -lactams) may be compromised.

Regardless of whether 104 or 107 organisms were present, time-kill investigations on clinical isolates of group G streptococci showed that when the bacteria was largely in log-phase development, the bacteria was quickly and completely killed. As opposed to this, quick and total killing was only seen for the smaller inoculum (104 organisms) and at 108 organisms, no killing was visible when the organism was primarily in the stationary phase. Additionally, despite high medication doses and the availability of a susceptible isolate, therapy failed in patients with resistant infections or lengthy clinical episodes of illness.