Synergistic Effect of a Novel Focal Hyperthermia on the Efficacy of Rifampin in Staphylococcal Experimental Foreign-Body Infection

Abstract

This study was designed to evaluate the efficacy of focal hyperthermia and rifampin in vitro and in vivo using a rabbit model of foreign-body infection by methicillin-resistant Staphylococcus aureus (MRSA). In vitro studies demonstrated bacterial re-growth and development of rifampin resistance after 24 h with rifampin alone, which was prevented under hyperthermic conditions. For the in vivo studies, rifampin was administered intraperitoneally every 12 h for 7 days to rabbits with MRSA-containing cages implanted into their flanks. When combined with hyperthermia at 39 degrees C, 41 degrees C and 43 degrees C, rifampin significantly reduced in-cage bacterial counts by > 3.0 log(10) colony forming units/ml compared with rifampin alone. Eradication of cage-associated infection was achieved more effectively when rifampin was combined with hyperthermia, with cure rates of 70-95% on day 10. Focal hyperthermia combined with rifampin prevented the emergence of rifampin resistance and maintained rifampin efficacy. These findings might have implications for orthopaedic surgery.

Using biofilms as initial inocula in animal models of biofilm‐related infections

“…Currently, combination biomaterials and coatings are being developed for the treatment and prevention of biofilm‐related infections. The majority of animal studies that are used to model infections related to these materials primarily involve the use of an initial inoculum of planktonic bacterial cells from batch cultures 1–24. The expectation has been that these planktonic cells would attach to the surface of a biomaterial, medical device, or surrounding tissue and subsequently form a biofilm.…”

Experimental model of biofilm implant‐related osteomyelitis to test combination biomaterials using biofilms as initial inocula

“…After a careful literature review, it appears that currently, the majority of animal models that are used to study biofilm‐related infection use planktonic bacterial cells as initial inocula to produce positive signals of infection 1–24. The expectation has been that planktonic bacteria would, depending on the animal model, attach to host tissue or a medical device and subsequently form a biofilm.…”

“…However, although the value of these animal models cannot be underestimated, the use of planktonic bacteria as initial inocula has provided inconsistent results in the repeatability of infection development. More specifically, results have shown that when planktonic cells are used as initial inocula, without any antimicrobial intervention, rates of infection are inconsistent between ∼47 and 100% 1–24. In addition to these inconsistencies, these models have potentially limited biomaterials scientists, clinicians, and other investigators from obtaining additional insights into the effect that bacteria might have if they contaminate a site while residing in well‐established, mature biofilms.…”

Are infectious diseases and microbiology new fields for thermal therapy research?

“…Additionally, combinations of heat therapy with antimicrobial drugs may have synergistic effects on infections with different kinds of isolates. Even if there are some reports investigating the synergistic effect of hyperthermia on the efficacy of some antibiotics, these studies are limited to a few bacterial strains (especially Staphylococcus aureus) and they do not recommend performing heat synergy tests before starting hyperthermia-plus-chemotherapy treatment [29,30]. One bacterial species, such as S. aureus, may have several biotypes with different physical and biochemical characteristics [47].…”

“…Therefore, as an alternative, local thermal therapies should be evaluated for the treatment of infectious diseases. In the literature, there are several reports indicating the potential of local heat therapy to treat bacterial infections [25][26][27][28][29][30].…”