Polymicrobial Foot Infection Patterns Are Common and Associated With Treatment Failure

That foot infections are predominately polymicrobial has long been recognized, but it is not clear if the various species co-occur randomly or in patterns. We sought nonrandom species co-occurrence patterns that might help better predict prognosis or guide antimicrobial selection.

We analyzed tissue (bone, skin, and other soft tissue), fluid, and swab specimens collected from initial foot infection episodes during a 10-year period using a hospital registry. Nonrandom co-occurrence of microbial species was identified using simple pairwise co-occurrence rates adjusted for multiple comparisons, Markov and conditional random fields, and factor analysis. A historical cohort was used to validate pattern occurrence and identify clinical significance.

In total, 156 unique species were identified among the 727 specimens obtained from initial foot infection episodes in 694 patients. Multiple analyses suggested that Staphylococcus aureus is negatively associated with other staphylococci. Another pattern noted was the co-occurrence of alpha-hemolytic Streptococcus, Enterococcus fecalis, Klebsiella, Proteus, Enterobacter, or Escherichia coli, and absence of both Bacteroides and Corynebacterium. Patients in a historical cohort with this latter pattern had significantly higher risk-adjusted rates of treatment failure.

Several nonrandom microbial co-occurrence patterns are frequently seen in foot infection specimens. One particular pattern with many Proteobacteria species may denote a higher risk for treatment failure. Staphylococcus aureus rarely co-occurs with other staphylococci.