# ORTHOPEDIC SEPSIS: PATHOGENESIS, DIAGNOSIS AND TREATMENT

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 1989 · $143,738

## Abstract

The long-term objectives of this application are to elucidate the
pathological alterations which permit musculoskeletal sepsis to
occur and utilize the knowledge of the pathological mechanisms to
improve the treatment of musculoskeletal sepsis.  This application
specifically addresses two types of musculoskeletal sepsis:  acute
hematogenous osteomyelitis (A.H.O.) and the infected total hip
arthroplasty.  There are five specific aims:  1) A.H.O. is caused by
an alteration of the host defense mechanism; 2) A.H.O. occurs
when the oxygen tension in the epiphyseal-metaphyseal junction is
reduced; 3) reduction of the oxygen tension inhibits leukocyte
interaction with tissue based macrophages; 4) concomittant
therapy of antimicrobials with substances that enhance cell
membrane fluidity such as pentoxifylline which locally increases
chemotaxis and phagocytosis can be currative of A.H.O.; and 5) a
delayed, two-staged reconstruction of the infected total hip
arthroplasty with an ingrowth arthroplasty is superior and safer
than a one-staged reconstruction with antibiotic impregnated
bone cement.

Aims one and two will be accomplished using the rabbit model of
A.H.O. described by Morrissy using light microscopy and
transmission electron microscopy, as well as, direct in vivo
oxygen tension measurements.  It is hypothesized that the absence
of peripheral polymorphonuclear leukocytes in the area of the
growth plate leaves the responsibility for bacterial phagocytosis
and killing of bacteria transported to this anatomic location
during a bacteremia to the tissue-based macrophages.  Trauma
further reduces the very low oxygen tension.  Preliminary
ultrastructural studies document growth of bacteria in the
traumatized zone of provisional calcification.   The third and
fourth aims will use the rat model of A.H.O. to permit the use of
available monoclonal antibodies to define the leukocyte
phenotypes and the interaction of lymphocytes and monocytes
with tissue based macrophages as well as perivascular cells.  The
final aim will be addressed in a canine model of a gram-negative
bacillary infection about a cemented total hip arthroplasty.  It is
hypothesized that a one-stage procedure fails to remove all of the
glycocalyx and bacteria from the bony femur and acetabulum
accounting for a reported failure rate of up to 50%.  In contrast, a
two-stage procedure with removal of all foreign material permits
the host-defense mechanism to eradicate any remaining bacteria
following excision of the arthroplasty.

## Key facts

- **NIH application ID:** 3155472
- **Project number:** 5R01AR026928-09
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **SAM.gov UEI:** Y2K4F9RPRRG7
- **Principal Investigator:** ROBERT H FITZGERALD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $143,738
- **Award type:** 5
- **Project period:** 1980-04-01 → 1990-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155472

## Citation

> US National Institutes of Health, RePORTER application 3155472, ORTHOPEDIC SEPSIS: PATHOGENESIS, DIAGNOSIS AND TREATMENT (5R01AR026928-09). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155472. Licensed CC0.

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