Abstract: Vancomycin was used alone and in combination with rifampin in the treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Treatment with 60 mg of vancomycin/kg of body weight twice a day for 28 days was ineffective in sterilizing infected rabbit bones. Rifampin (40 mg/kg) injected once a day for 28 days sterilized 57% of infected rabbit bones. Treatment with a combination of vancomycin and rifampin for either 14 or 28 days was significantly more effective than either drug used alone, sterilizing 84% and 90%, respectively, of the infected bones of treated animals. A possible explanation for the failure of vancomycin when used alone may be that its in vitro activity against the infecting strain of S. aureus (as measured by minimal inhibitory concentrations or minimal bactericidal concentrations) was substantially less under anaerobic conditions (that is, at partial pressures of oxygen analogous to those in osteomyelitic bones) than under aerobic conditons. In previous studies using an experimental model of chronic staphylococcal osteomyelitis, antibiotic therapy in which rifampin was combined with an aminoglycoside or with cephalothin was significantly more effective than single-drug therapy [1]. However, the optimal treatment for this disease remains enigmatic, and further studies are clearly indicated. Vancomycin is an effective antistaphylococcal agent [2-4] and has potential attractiveness in the treatment of a chronic infectious disease-such as osteomyelitis caused by Staphylococcus aureus-because it can be administered less frequently than many other antimicrobial agents while maintaining comparable effectiveness. Rifampin has a unique ability to kill intraleukocytic bacteria [5], has already proved ef

Abstract: Sixteen patients with serologically proven Q-fever infection are reviewed. Fifteen had significantly raised antibody titres to both phase I and phase II Coxiella burneti antigens, indicating persistent or chronic infection. One patient, a premature infant who died, had raised phase II titres only, but is included together with the mother who had chronic Q-fever and was the presumed source of infection. Chronic Q-fever infection has previously been regarded as virtually synonymous with Q-fever endocarditis, but only seven of the patients in this survey had evidence of valvular endocarditis. In those who did, the infection had arisen on prosthetic valves or those affected by rheumatic or syphilitic heart disease. One patient had inexorably progressive destruction of an infected congenitally bicuspid aortic valve. Eight patients had infections associated with extra-valvular sites and several of these associations have not been previously described. These include extreme prematurity with perinatal death, possibly following transplacental infection, the sudden infant death syndrome (SIDS), multiple lower limb emboli from endocarditis of an abdominal aortic dacron graft, and colonization of ventricular endocardium following left ventricular myotomy/sub-aortic diaphragm resection. The current concept that chronic Q-fever is invariably associated with endocarditis is therefore untenable and the indications for phase I antibody screening should be extended to include patients other than those under investigation for ‘culture-negative’ endocarditis, for example those with unusual osteomyelitis of vertebrae.

Abstract: We reviewed the technetium phosphate scans of 280 patients who had been referred with a clinical diagnosis of osteomyelitis in order to establish the diagnostic accuracy of this procedure. Strict criteria were established to define two subgroups: one of patients with proved osteomyelitis and one of patients who definitely did not have osteomyelitis. The scan correctly identified osteomyelitis at fifty-five of sixty-two sites, and was correctly negative in seventy-four of seventy-nine patients without osteomyelitis. The scan correctly distinguished all cases of cellulitis or soft-tissue abscess from osteomyelitis, but identified osteomyelitis in eight of thirty-nine patients with septic arthritis. The phosphate bone scan maintained this accuracy through any duration of symptoms, and performed almost equally well at all skeletal sites and in all age groups.

Abstract: A simple and reproducible avian model of acute hematogenous osteomyelitis is described, and the natural history of the disease has been documented. Infection was induced by intravenous injection of bacteria. Chickens were killed 6, 12, 24, 48, 96, and 192 hours following bacterial inoculation, and the left proximal tibia and distal femur were removed for histologic examination. Bacterial deposition initially occurred within the growing ends of metaphyseal tunnels in the hypertrophic region of the zone of cartilage transformation in the growth plate. Bacterial proliferation occluded the vascular tunnel within 24 hours. The initial deposition of bacteria, the subsequent spread, and the nature of the inflammatory process are discussed in relation to the vascular arrangement adjacent to the growth plate. The frequent formation of sequestrum and the effect on the growth plate of an adjacent abscess is described.

Abstract: Computed tomography (CT) is now used extensively for the evaluation of orbital, facial, and intracranial infections. Nine patients are presented to illustrate the importance of detecting underlying and unsuspected sinusitis. Prompt treatment of the sinusitis is essential to minimize the morbidity and mortality associated with complications such as brain abscess, meningitis, orbital cellulitis, and osteomyelitis. A review of the literature documents the persistence of these complications despite the widespread use of antibiotic therapy. Recognition of the underlying sinusitis is now possible with CT if the region of the sinuses is included and bone-window settings are used during the examination of patients with orbital and intracranial infection.

Abstract: SUMMARY A single strain of Staphylococcus aureus was used to study the pathogenesis of osteomyelitis in chickens. The disease was consistently reproduced in 6-week-old broiler chickens when 1 X 105 or more organisms were given intravenously. Severe feed restriction, debeaking, and single or multiple injections of corticosteroids delayed the appearance and decreased the severity of lesions due to staphylococcal infection. This increased resistance was associated with increased numbers of circulating heterophils and monocytes. No correlation between the presence of tibial dyschondroplasia

Abstract: Experience with rifampin as a component of combination antibiotic therapy for chronic staphylococcal osteomyelitis was reviewed. These data included the preliminary results of a randomized, prospective trial of parenteral nafcillin alone vs. parenteral nafcillin plus oral rifampin; the results of use of rifampin in combination with other oral antibiotics for the treatment of chronic staphylococcal osteomyelitis; and experience with rifampin regimens at the Oregon Health Sciences University. A total of 28 patients are described in this report; 70% of those who received regimens including rifampin experienced an apparent cure of infection. Most patients whose infections were not cured had inadequate surgical therapy or were also infected with other bacteria. Staphylococcus aureus was eradicated from the sinus drainage of all but one patient. Although these results are encouraging, a larger number of patients and a longer follow-up period are required for an adequate evaluation of the place of rifampin in therapy for chronic staphylococcal osteomyelitis.

Abstract: 10 patients with serious infections caused by Staphylococcus epidermidis (8 cases of endocarditis in non-prosthetic valves, 1 was complicated by osteomyelitis, 1 case of osteomyelitis, and 1 case of septicemia) are described. Clinical and microbiologic features were evaluated including antibiotic sensitivity and synergy studies, phage typing and biotyping. Endocarditis tended to affect the elderly population and the clinical manifestations were quite similar to those caused by Streptococcus viridans. Both patients with osteomyelitis had involvement of the cervical spine with excellent response to antibiotic therapy. The only patient with septicemia acquired via hyperalimentation had delayed clearance of the bacteremia but ultimately responded to intravenous antibiotics. Rifampicin was the most effective of all antibiotics tested. All isolates were sensitive to penicillinase-resistant penicillins and cephalosporins and over half were sensitive to penicillin. Full synergistic activity was demonstrated with ...

Abstract: The efficacy of rifampin alone and in combination with sisomicin, cephalothin, sisomicin and cephalothin, or trimethoprim was measured in an experimental model of chronic osteomyelitis due to Staphylococcus aureus in rabbits. Single-drug regimens used for 28 days were relatively ineffective (bone sterilization rate, 5%-55%). Combinations of rifampin with other agents were more effective (bone sterilization rate, 75%-100%). The combination of rifampin, sisomicin, and cephalothin given for only 14 days sterilized the bones of all treated rabbits. Staphylococci isolated from the bones of rabbits that had received rifampin alone or in combination with other antibiotics were highly resistant to rifampin; in contrast, these organisms remained sensitive to the other agents used. Results of in vitro studies of synergy correlated with in vivo results in some but not all instances. The results obtained with rifampin in the treatment of experimental chronic osteomyelitis caused by S. aureus suggest that clinical trials of this agent for the treatment of osteomyelitis in humans are warranted.

Abstract: Psoas muscle abscesses are a diagnostic and therapeutic challenge. Until recently, surgery was mandated for diagnosis and drainage of these deep posterior lesions. Scanning techniques such as computerized tomography, radionuclide imaging, and ultrasonography now enable noninvasive visualization of abnormalities of the psoas muscle. Patients with abscesses in the greater psoas muscle fall into two distinct groups. Six of 12 patients reviewed had no apparent predisposing conditions. These patients presented with subacute symptoms of fever, pain, and disability. Staphylococcus aureus was the predominant organism isolated. Psoas infections developed in six other patients secondarily to infection or trauma elsewhere in the abdomen. Gram-negative and enteric organisms were the predominant bacteria isolated from this group. Surgical drainage in selected patients and appropriate antimicrobial therapy is necessary for treatment of these infections. Late complications such as osteomyelitis are not unusual.

Abstract: Computed tomography (CT) were performed in 17 adults with osteomyelitis of the spine. The dominant features were paravertebral soft-tissue swelling, abscess formation, and bone erosion. In two patients there were no findings indicative of osteomyelitis on conventional radiographs, but CT revealed paravertebral abscesses and bone lysis, helping to establish the diagnosis of osteomyelitis. CT was found helpful in the evaluation of the patients suspected of spinal osteomyelitis, chiefly because of its ability to detect early erosion of spongy vertebral bone, disk involvement, paravertebral soft-tissue swelling or abscess, and extension of the pathology into the spinal canal. Furthermore, CT facilitated closed-needle biopsy, helping to establish the pathologic diagnosis.

Abstract: A simple and reproducible model of acute haematogenous staphylococcal osteomyelitis is described. Twenty-nine day-old chickens were inoculated intravenously with 10(4)-10(8) viable organisms Staphylococcus aureus per kg body weight and were killed 1-8 days after inoculation. Macroscopic septic foci could be detected within 24 hr of inoculation and were most commonly situated in the metaphyseal region of the proximal tibia and distal femur. Lesions in other organs were not observed. The production of osteomyelitis was dependent on the bacterial inoculum size. It was estimated that 5.5 X 10(5) viable organisms per kg body weight of chicken were required to produce osteomyelitis in 50 per cent of injected chickens. Chicken weights were monitored throughout the experiment. A close negative correlation existed between the logarithm of the bacterial inoculum size and the chicken growth rate in the first 24 hr following inoculation (r = -0.968, P less than 0.01). The chicken growth rate was therefore used as an accurate predictor of osteomyelitis in individual chickens.

Abstract: •Kingella (Moraxella) kingaeoccasionally colonizes the nasopharynx and rarely causes serious infections. Three children withK kingaeinfections treated over a two-month period were studied. Epidemiologic investigation concluded that infection was community acquired, not pseudoinfection or nosocomial infection. Except for prompt laboratory recognition of the organism, no identifiable factors explained the observed prevalence. Five additionalK kingaeinfections were reviewed. Affected sites included blood (two), valves (two), bone (two), joint (one), and disk space (one). Three patients had underlying disease; one was immunosuppressed.Kingella kingaeresembles other members of the Neisseriaceae family and causes similar infections except meningitis. It is differentiated by colonial characteristics and standard biochemical tests. Treated infections responded to penicillin G potassium. Gram-negative bacteria uncommonly are implicated in endocarditis, arthritis, osteomyelitis, and diskitis;K kingaedeserves recognition as a pathogen in these pediatric infections. (Am J Dis Child1983;137:650-653)

Abstract: Five cases of chronic, inflammatory, multifocal bone lesions of unknown etiology are reported. Although bone biopsy confirmed osteomyelitis in each case in none of them were organisms found inspite of an extensive work up. Different clinical course of the disease reflects different aetiology in respective cases. These cases present changing aspects of osteomyelitis emerging since introduction of antibiotics.

Abstract: A 720-g premature newborn developed disseminated candidiasis during treatment with systemic antibiotics and total parenteral nutrition through an umbilical arterial catheter. Clinical features were typical for candidal skeletal infection at this age and included warmth and fusiform swelling of the lower extremities together with radiographic evidence of osteolysis and cortical bone erosion. Candida albicans was cultured from blood, urine, joint fluid, and a bone aspirate. The infection was cured with a 44-day course of amphotericin B and flucytosine (5-fluorocytosine). Antifungal therapy was monitored closely with serum drug levels and laboratory tests for bone marrow toxicity and renal dysfunction. Serum levels of both drugs were comparable to those achieved in older patients treated with similar doses. Significant concentrations of amphotericin B were detected in serum four and 17 days after completion of therapy, indicating a slow rate of elimination similar to that which occurs in adults. There was no evidence of drug-induced toxicity other than transient elevation in the fractional urinary excretion of sodium. This suggests that antifungal therapy may be effectively and safely administered to infants in dose schedules similar to those used for older patients.

Abstract: Six patients with bacteriologically proven pyogenic osteomyelitis of the spine were followed serially with computed tomography (CT). Initial evaluation of the involved vertebral bodies and adjacent soft tissues showed a drop in CT numbers when compared to normal cancellous bone and soft tissues. A soft-tissue mass was seen in all cases. After appropriate antibiotic therapy, all six patients showed an increase in bone density and a diminution of the soft-tissue mass (p less than 0.05). Five of the six patients showed a further decrease in soft-tissue CT numbers.

Abstract: Osteomyelitis of the clavicle is rare; however, it may occur following head and neck surgery. Risk factors include radiation, long-standing tracheitis, disruption of the periosteum or the cortical bone with interruption of the blood supply to the clavicle. Proper management includes early diagnosis, surgical debridement of soft tissue and bone, appropriate antimicrobial therapy, and coverage of the defect with a myocutaneous flap to protect the great vessels of the upper mediastinum.

Abstract: Groups of 6-week-old broiler chickens were exposed to Staphylococcus aureus by aerosol, intratracheal or intravenous (control) inoculation. No lesions were produced by aerosol. A single dose of up to 5 X 10(10) organisms given intratracheally failed to produce any lesions. Single or repeated doses of 5 X 10(11) organisms given intratracheally resulted in osteomyelitis in a low proportion of chickens.

Abstract: • Osteomyelitis of the clavicle is an uncommon complication of Swan-Ganz catheterization. The diagnosis should be suspected when the clinical features of fever and sternoclavicular pain are present. Traditional roentgenograms may be falsely normal early in the disease. Radioactive isotope scanning may be helpful in establishing the diagnosis sooner, followed by tomography or computed tomography to better define the abnormality. Therapy should include long-term parenteral antibiotics and possible surgical removal. ( Arch Intern Med 1983;143:153-154)

Abstract: A rabbit model for Staphylococcus aureus osteomyelitis was used to compare the results of twenty-eight days of treatment with cefamandole or cephalothin. Cultures of bone were positive for Staphylococcus aureus in eleven of eleven controls, nine of thirteen cefamandole-treated animals, and seven of fifteen cephalothin-treated animals. Both treatment groups differed from the untreated controls (p < 0.05), but there were no differences between the treatment groups. However, the cephalothin-treated group had lower mortality, greater weight gain, and decreased severity of bone destruction by gross and radiographic indices. Concentrations of cefamandole in bone were higher than those of cephalothin in both normal and infected bone (p < 0.05). However, greater /3-lactamase stability of cephalothin compared with cefamandole or cefazolin was shown by inactivation studies and by high and low-dilution sensitivity studies. Using multiple assessments, cephalothin appears to be superior to cefamandole for eradication of this Staphylococcus aureus from infected bone. CLINICAL RELEVANCE: Many variables must be considered when one attempts to evaluate antibiotic studies in patients with osteomyelitis. The rabbit model of osteomyelitis that was developed by Scheman et al. and refined by Norden and 18 eliminated the majority of these variables. This animal model of Staphylococcus aureus osteomyelitis can be extremely useful in orthopaedic research. In this study, we demonstrated that cephalothin is superior to cefamandole for the treatment of experimental Staphylococcus aureus osteomyelitis. Staphylococcus aureus is the pathogen most often involved in bone infections. Cefamandole provided higher bone concentrations than cephalothin, but cefamandole was less stable to the elaborated f3-lactamase of this Staphylococcus aureus. /3-lactamase production by this Staphylococcus aureus may account for the failure of some animals to respond Read in part at the Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, Illinois, November 6, 1981. t Supported by a grant from Eli Lilly and Company, Indianapolis, Indiana, and by the Marine Biomedical Institute, Galveston, Texas. : Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, Texas 775502772. to cefamandole therapy. Cephalothin was stable to high inocula of Staphylococcus aureus and filterable /3-lactamase. It is difficult to extrapolate from rabbit to human, but cephalothin appears to be superior to cefamandole for the treatment of osteomyelitis when Staphylococcus aureus is involved in the infection. Cefamandole is a second-generation cephalosporin with excellent in vitro activity against Staphylococcus aureus4’5’25. In vitro studies with cefamandole have shown excellent antibacterial activity against most streptococci, Escherichia c’oli, and Klebsiella species, and significant activity agai nst most other I 4,22 Cli nically, cefamandole has been effective in the treatment of septicemia, lower respiratory-tract infections, urinary tract infections, peritonitis, skin structure infections, and other miscellaneous infections’ . However, little experimental or clinical data are available to evaluate cefamandole in the treatment of osteomyelitis. To be effective in osteomyelitis, a single broad-spectrum antibiotic must be capable of eradicating Staphylococcus aureus, which is the most common isolate from infected bone23. In order to reduce the variables of a clinical antibiotic study, the rabbit model of Staphylococcus aureus osteomyelitis developed by Scheman et al. and refined by Norden and Kennedy’8 was utilized. The model produces a progressive osteomyelitis that is accompanied by periosteal reaction, lytic bone lesions, sequestra, and involucra. In this model a solution of 5 per cent sodium morrhuate, a mild sclerosing agent, is injected directly into the tibial metaphysis of a rabbit. This injection is followed by an injection of /3-lactamase-producing Staphylococc’us aureus which is followed by saline. Crane et al., in detailed histological studies, observed abscess formation at the site of injection which was surrounded by an exudate composed chiefly of polymorphonuclear leukocytes and an advancing zone of edema. The infection spreads proximally and distally to involve the entire tibia. Progressive destruction of bone with sequestrum formation is present by fourteen days. The model has previously been used to evaluate cephalothin’5 ’9 and cephaloridine ‘ A controlled study utilizing the Staphylococcus aureus osteomyelitis model was performed to compare the . . . . Visual and Radiographic Evaluation ment ofStaphylococcus aureus osteomyehtls then, wlth lts enhanced coverage of gram-negative aerobic organisms, it would be an ideal antibiotic for the treatment of contiguous-focus osteomyelitis or chronic osteomyelitis . These types of osteomyelitis are usually polymicrobial, with Staphylococcus aureus often being one of the isolates. Materials and Methods THE JOURNAL OF BONE AND JOINT SURGERY 508 J. 1. MADER AND K. J. WILSON effectiveness of cefamandole and cephalothin. Cephalothin is the standard first-generation cephalosporin and is frequently used to treat Staphylococcus aureus osteomyelitis. If cefamandole proved effective in the treat-

Abstract: Osteomyelitis due to M. avium is extremely rare and frequently fatal. the successful cure of an 11-year-old patient with multiple mycobacterial lesions in the pelvis and right humerus is reported. Although the mycobacteria were in vitro resistant to most antituberculous drugs a five-drug regimen was given over a total of 2½ years. the accumulated streptomycin dose was 160 g but no adverse effects were noted. Streptomycin therapy was judged of major importance for the favourable outcome.

Abstract: Actinomyces israelii is a part of the human oral flora and thus is more commensal than pathogenic. Oral trauma, accidental or purposeful, can precipitate its introduction into the soft tissues, to which infection is usually confined. The case presented is one in which, over a span of two decades (1956 to 1977), the extraction of a mandibular tooth resulted in a chronic actinomycotic osteomyelitis, destroying first the mandible, then both maxillae, and then the right zygoma, with decreased vision and proptosis despite repeated medical and surgical intervention. Adequate treatment required removal of the sequestrum and excision of all infected granulation tissue, scars, and involucra until healthy bone was exposed. Intravenous penicillin was administered for 2 weeks, followed by a 6-month course of oral penicillin. The patient was followed for 4 years and remained disease free.

Abstract: A 31-year-old man had a maxillary sinus infection and osteomyelitis In vitro lymphocyte transformation studies indicated that he had a specific immune tolerance to Alternaria organisms The etiologic agent was recovered and was identified as Alternaria alternata