Vertebral osteomyelitis due to salmonellae: report of two cases and review.

We describe two patients with salmonella vertebral osteomyelitis (SVO) and review 44 cases in the English-language literature. There was male predominance (distribution, 1.7:1), primarily lumbar involvement (72% of cases), and monomicrobial etiology. Fever (87% of cases) and back pain (92% of cases) were the dominant signs and symptoms, while diarrhea was present only in 16% of cases. Blood culture was positive in 48% of cases, and stool and urine cultures were positive in 36% and 23% of cases, respectively. The overall cure rate was 61%, and the relapse rate was 9%. Infected abdominal aortic aneurysms (IAAAs) were seen exclusively in the older age group (50 years of age or older), and all deaths occurred in these patients. The mean duration of antibiotic use for patients who were cured was 60 days. Although SVO is primarily treated medically, certain cases may require individualized surgical intervention. Patients with concomitant IAAAs may need resection with thorough debridement, extraanatomic bypass grafting, and prolonged antibiotic therapy.

Bone and joint infections in patients with infective endocarditis: review of a 4-year experience.

Musculoskeletal complaints have been reported to occur in as many as 44% of patients with infective endocarditis (IE). A 4-year retrospective review of 104 cases of IE in which new diagnostic criteria were used showed that 24 episodes (23%) began with musculoskeletal complaints. Sixteen of the 24 episodes (66%) involved osteoarticular infection (OAI) documented during the period of hospitalization. Thus, in 15% of the 104 cases of IE, OAI was documented. The 16 episodes occurred in 15 patients, all of whom were intravenous drug abusers (IVDAs). In contrast, OAI was documented in none of the 38 cases in the IE population that did not involve IVDAs. Only three episodes were associated with single rather than multiple bone or joint involvement. There were no deaths, and the patients' conditions seemed to respond well to appropriate therapy. OAIs appear to be uncommon in patients with IE who are not IVDAs. Musculoskeletal complaints in the IVDA population with IE, however, should prompt a careful search for OAI.

Microbiology and antimicrobial therapy of spinal infections.

Hematogenous vertebral osteomyelitis is almost always a monomicrobial infection affecting predominantly the older population. S. aureus is the most common micro-organism isolated. Gram-negative bacilli, however, are seen primarily in elderly males with the urinary tract as the source of infection, as well as in IVDA. In the latter group, P. aeruginosa, as well as S. aureus, are the dominant microorganisms. The offending organisms are generally isolated by needle biopsy, using a cutting needle, or by open surgical biopsy when necessary. Spinal epidural abscesses have very similar microbiology. Antimicrobial therapy is generally given parenterally in high doses, together with surgical evacuation of abscesses and debridement of necrotic tissue, when necessary. Therapy may be guided by the ESR. In VO, when the patient is doing clinically well and the ESR decreases to at least half of the pretherapy value, therapy may be stopped, but continued elevation of the ESR and the presence of abscesses may necessitate more prolonged therapy. The role of oral antimicrobial therapy is currently unclear.

Preliminary study using species-specific oligonucleotide probe for rRNA of Bilophila wadsworthia.

Portions of the 16S RNA from a urease-positive Bilophila wadsworthia strain were sequenced, and a probe was constructed. The probe was end labeled with [32P]ATP and polynucleotide kinase and hybridized on a nylon filter (by dot blot hybridization) to the immobilized rRNA of 12 B. wadsworthia strains and eight other anaerobic isolates. The probe efficiently hybridized only to the Bilophila strains. Cross-reactivity at high RNA levels (2,000 ng) was observed with one strain of Bacteroides thetaiotamicron and one strain of Bacteroides fragilis (with 10x SET buffer [20x SET buffer is 0.5 M NaCl, 0.03 M Tris, and 2 mM EDTA]) but was not seen at lower RNA levels or with 5x SET buffer. When tested against mixed cultures of aerobic and anaerobic isolates representative of appendiceal abscess flora, the probe did not react with mixed cultures containing no Bilophila cells and could detect > or = 10(5) Bilophila CFU/ml when the mixture was seeded with Bilophila cells. This probe is of potential use in the rapid identification of pure isolates and in the direct identification of B. wadsworthia in clinical specimens.

Infections in the diabetic patient: the role of immune dysfunction and pathogen virulence factors.

It is a common belief that certain infections occur more frequently in patients with diabetes mellitus than in nondiabetics. In some infections, poor diabetic control is strongly linked. Diabetics comprise 50%-70% of all patients who undergo nontraumatic foot or leg amputations, the overwhelming majority of which are necessitated by infection and necrosis of soft tissue and/or bone. Imputed host defense abnormalities include defective immune responses (e.g., white blood cell function, granuloma formation), peripheral neuropathies, impaired distal arterial supply, and problems in "control" of the diabetic state eventuating in catabolic metabolism. Increased bacterial translocation as a source of the causative bacteria is another potential entry site. Possible virulence factors of the invading organisms include polymicrobial synergism, glycocalyx formation, and inoculum size. Attention to the principles of preventive education, vascular evaluation, diabetes management, and adequate debridement maximize healing potential.

Low mortality among patients with spinal cord injury and bacteremia.

We reviewed 103 episodes of bacteremia in 93 patients with spinal cord injury who had bacteremia during initial hospitalization (39 patients) or readmission (54 patients) during 1978-1988. Eighteen episodes (18%) were due to polymicrobial infections. Urinary tract infections (47%), infected pressure areas (19%), and pneumonia (9%) were the most frequent primary infections and sources of the bacteremia. The bacteria most frequently associated with urinary tract infections were enterococci (26%), Escherichia coli (26%), Pseudomonas species (20%), and Klebsiella pneumoniae (12%). Bacteria most frequently isolated from patients with infected pressure areas were anaerobes and Staphylococcus aureus. Bacteremia was the cause of death for 8 patients (9%). The urinary tract was identified only once as the source of gram-negative bacteremia in an immunocompetent patient who died. The reason for the low mortality in patients with spinal cord injury is unclear.

Comparison of Enterococcus raffinosus with Enterococcus avium on the basis of penicillin susceptibility, penicillin-binding protein analysis, and high-level aminoglycoside resistance.

We reidentified our laboratories' collections of 57 enterococcal isolates previously classified as Enterococcus avium by the API Rapid Strep identification system (Analytab Products, Plainview, N.Y.) with the identification criteria recommended by Facklam and Collins (R. R. Facklam and M. D. Collins, J. Clin. Microbiol. 27: 731-734, 1989). Thirty isolates were identified as true E. avium, 25 isolates were identified as E. raffinosus, and 2 isolates were identified as E. pseudoavium. E. raffinosus could be differentiated from E. avium on the basis of penicillin susceptibility, as follows: MIC for 50% of E. raffinosus isolates tested (MIC50), 32 micrograms/ml; MIC90, 64 micrograms/ml (range, 4 to 64 micrograms/ml); E. avium MIC50, 1 microgram/ml; MIC90, 2 micrograms/ml (range, 0.5 to 2 micrograms/ml). No strains produced detectable beta-lactamase. Penicillin-binding protein (PBP) analysis of all E. raffinosus isolates demonstrated the unique pattern reported previously (M. D. Collins, R. R. Facklam, J. A. E. Farrow, and R. Williamson, FEMS Microbiol. Lett. 57:283-288, 1989); however, a number of newly identified PBPs were noted. Of 25 isolates, 13 had an additional PBP of 77 kDa (designated PBP 6*), while all isolates possessed a 52-kDa PBP (PBP 7) and a 46-kDa PBP (PBP 8). The presence or absence of PBP 6* did not correlate with penicillin susceptibility; however, PBP 7 demonstrated many features suggestive of low penicillin-binding affinity and may represent a possible mechanism for the relative resistance of this species to penicillin, although this hypothesis remains speculative since attempts to develop a penicillin-hypersusceptible E. raffinosus mutant were unsuccessful. E. raffinosus isolates were significantly more likely to exhibit high-level resistance to kanamycin than E. avium strains were (P < 0.001; chi-square); however, no strains demonstrated high-level resistance to gentamicin. No trend toward increasing penicillin resistance was noted among this collection of E. avium and E. raffinosus isolates collected over the past 35 and 14 years, respectively. Relative resistance to penicillin may be a helpful differentiating feature between E. avium and E. raffinosus when assessment of raffinose metabolism is not possible or is indeterminant.

Cefpirome, alone and in combination with gentamicin for enterococcal pyelonephritis in the rodent model.

The in vitro and in vivo activity of cefpirome (CF) against Enterococcus faecalis GK strain was examined. The ratio of minimal inhibitory to bactericidal concentration (MIC/MBC) values in microgram/ml were (a) ampicillin 0.8/1.5; (b) gentamicin 2/25; (c) vancomycin, 0.8/50; and (d) CF, 8/32. A time-kill study using 10(7) organisms per milliliter showed a drop of 3 logs10 at 4 hr in the tube containing cefpirome (10 micrograms/ml) as well as the tube containing cefpirome (5 micrograms/ml) plus gentamicin (GM) (2 micrograms/ml), as compared to the control and the tube containing GM at 4 micrograms/ml. At 8 and 24 hr, however, regrowth to control levels occurred. Of this enterococcal strain consisting of 10(8) organisms, 1 ml was then injected intravenously by tail vein into 150 male Wistar rats weighing 120 g each. Eleven days after injection, 10 rats were killed and the remaining ones were randomized into four treatment groups: (a) untreated control; (b) BM, 0.9 mg; (c) CF, 10 mg; and (d) CF + GM. The rats received the injections intramuscularly twice daily. At least 10 rats from each group were killed for quantitative kidney cultures at 1, 2, and 4 weeks after start of therapy. At the end of 4 weeks of therapy, the results were significantly better in the combination group compared to the other three groups.

Vertebral osteomyelitis.

Vertebral osteomyelitis can be caused by a variety of microorganisms. The hematogenous pyogenic form is characteristically a disease of people over age 50, predominantly in the male population, and most frequently caused by S. aureus. In IVDAs, however, younger patients and a heavier predominance of males are seen, and P. aeruginosa is one of the most commonly seen pathogens. The disease is generally monomicrobial, unless it is secondary to a contiguous process such as a pressure sore, in which polymicrobial infection with participation of anaerobes is the general rule. Lumbar, greater than thoracic, greater than cervical involvement is the rule in the general population, but cervical spine involvement is frequently seen more often than thoracic involvement in IVDAs. Diabetic patients are over-represented among patients with vertebral osteomyelitis, and they also have a tendency for higher morbidity and mortality. Simultaneous involvement of adjacent vertebral end plates and the intervening disk is the general rule. The vertebrae are generally involved, and the posterior elements of the spine are involved infrequently. Posterior element involvement is seen more commonly in actinomycosis, coccidioidomycosis, and neoplasms. Newer diagnostic modalities, such as CT, MRI, and radionuclide scans, may detect the disease earlier than conventional radiographs. Immunobilization by bed rest and appropriate antimicrobial therapy are generally sufficient in the therapy of pyogenic, as well as tuberculous, vertebral osteomyelitis. In selected circumstances, such as in the presence of marked instability of the spine, the presence of new neurologic deficits, or with progression of previous neurologic deficits, surgical intervention may be necessary. With prompt diagnosis and proper management, the prognosis should generally be good.

Foot infections in patients with diabetes mellitus.

Foot infection is the single most common reason for hospitalization of the diabetic patient. A combination of host factors, including neuropathy, angiopathy, and immunopathy, combine to make the diabetic foot infection the most severe infection commonly seen by podiatrists. If inadequately treated, the likelihood of morbidity or mortality is high. The presence of anaerobic bacteria as a predominant type of organism makes diagnosis and antibiotic selection complicated.

Enterococci highly resistant to penicillin and ampicillin: an emerging clinical problem?

Sixteen clinical isolates of ampicillin-resistant enterococci (ARE) were recovered from the microbiology laboratory of a 450-bed rehabilitation medical center from January 1981 to September 1987. These isolates were detected when a disk diffusion test using 10 micrograms of ampicillin on a blood agar plate revealed no zones of inhibition. Tube macrodilution tests yielded an MIC of greater than or equal to 16 micrograms of ampicillin per ml. None of the isolates were penicillinase producers by the chromogenic cephalosporin disk test. Ten isolates were Enterococcus faecium, four isolates were E. raffinosus, one isolate was E. gallinarum, and one isolate was not identified (lost). There were 6 male and 10 female patients. The sources of isolates were urine (n = 7), wound (n = 5), ascitic fluid (n = 2), blood (n = 2), peritoneal catheter tip (n = 1), Bartholin's cyst abscess (n = 1), rectal swab (n = 2), and pancreatic abscess (n = 1). The organism was isolated from multiple sites in 4 patients, was a pure culture isolate in 5 patients, and was part of a polymicrobial flora in 11 patients. Six patients were diabetic, and four had liver cirrhosis. All but four patients had received at least one antibiotic within 3 weeks of ARE isolation. The MICs (micrograms per milliliter) for 50 and 90% of isolates tested, respectively, were as follows: ampicillin, 64 and 64; penicillin, 128 and greater than 128; vancomycin, 1 and 2; gentamicin, 4 and 16; ciprofloxacin, 1.6 and 3.2; imipenem, 128 and greater than 128; and daptomycin (LY146032), 1.6 and 6.4. ARE may be an emerging pathogen in the hospitalized patient population.

Infections in the diabetic host.

The presence of the diabetic state seems to predispose patients to more severe and unusual types of infections. Awareness and early recognition of these sometimes devastating problems, coupled with appropriate medical and surgical treatment and aggressive metabolic control of diabetes, provide the maximum opportunity for healing and recovery.

Randomized controlled trial of topical hyperbaric oxygen for treatment of diabetic foot ulcers.

The effect of 2 wk of topical hyperbaric oxygen (THO) treatment on the healing of diabetic foot ulcers without associated gangrene was evaluated in a prospective, controlled, and randomized manner in 28 patients. There were 12 patients in the THO group (group 1) and 16 in the control group (group 2). Clinical management of the two patient groups was similar except for THO treatment in the group 1 patients. Clinical parameters, including age, sex, baseline fasting serum glucose levels, duration of diabetes mellitus, duration of foot ulcers, presence of peripheral neuropathy or arterial insufficiency, and evidence of osteomyelitis as determined by radiographs and/or radionuclide scans, were comparable in both groups of patients. No statistical differences (Student's t test) were seen in the number of microorganisms isolated from curettage cultures of the base of the ulcer at days 0, 7, and 14 of the study between groups 1 and 2. In contrast to previous studies, there was a paucity of anaerobic microorganisms isolated from these foot ulcers without associated gangrenous changes. Ulcer areas were estimated by multiplying the maximum width by the maximum length in millimeters at days 0, 7, and 14. Analysis of variance and Student's t test revealed progressive significant reductions in the ulcer areas in both groups when days 0, 7, and 14 were compared and in ulcer depths in both groups when days 0 and 14 were compared. However, such ulcer size changes did not differ statistically between the control and THO groups. A trend toward slower healing was observed in the THO group. Healing of diabetic foot ulcers was not accelerated by THO in this study.

LY146032, alone and in combination with gentamicin, for the treatment of enterococcal pyelonephritis in the rat model.

The in vivo and in vitro activity of LY146032 against Streptococcus faecalis GK was examined. The following MICs and MBCs in micrograms per milliliter were obtained: ampicillin, 0.8 and 1.5; vancomycin, 0.8 and 50; gentamicin, 12 and 25; and LY146032, 0.8 and 6. A time-kill-curve study involving approximately 10(6) organisms per ml showed a drop in the number of organisms of almost 2 log10 in the tube containing LY146032 (2 micrograms/ml) plus gentamicin (4 micrograms/ml) compared with bacterial numbers for the control at 4 h of incubation. However, regrowth was observed at 24 and 48 h, and no in vitro synergism was observed with the combination. A sample (1 ml) of overnight growth of this enterococcal strain at a concentration of 10(7) was then injected intravenously into 184 male Wistar rats weighing about 100 g each. After 12 days, 10 rats were sacrificed and the remaining ones were randomized into four treatment groups: (i) untreated control, (ii) LY146032 (3 mg) given subcutaneously, (iii) gentamicin (0.8 mg) given intramuscularly, and (iv) LY146032 plus gentamicin at the same dosages as when the drugs were used singly. The rats received antibiotics for 4 weeks twice daily, and approximately 10 rats in each group were sacrificed for quantitative kidney cultures at 1, 2, 4, and 6 weeks after the start of therapy. At the end of the 4- and 6-week periods, significantly better results were obtained with the combination of LY146032 plus gentamicin than with no treatment or treatment with single antibiotics.

Quantitative microbiology of pressure sores in different stages of healing.

The quantitative microbiology of 25 pressure sores in different stages of healing was examined in 25 patients with spinal cord injury. When grossly necrotic tissue was present (stage 1), 5.8 isolates per patient with a density of 6.4 log10/g was recovered, with comparable findings for aerobes and anaerobes. In the absence of necrotic tissue but with the presence of undermining (stage 2), 1.5 aerobic and 0.2 anaerobic isolates were recovered per patient with a mean density of 2.7 and 0.1 log10/g of tissue for aerobic and anaerobic isolates, respectively. The lesions were almost sterile in patients with no necrotic tissue and no undermining (stage 3). Foul smell was always associated with the presence of anaerobes in deep tissue cultures, however, six patients with nonfoul-smelling lesions yielded anaerobes. A 75% quantitative concordance was seen between swab and biopsy culture results. The quantitative concordance between peripheral and central biopsy culture results was 63%, showing variability in results from different sampling areas. No relationship was observed between the density of microorganisms and the eventual outcome of the myocutaneous flap procedure.

Osteomyelitis associated with pressure ulcers.

Bone biopsies were performed in spinal cord injured patients with pressure ulcers in whom osteomyelitis was suspected. Roentogenograms and bone and gallium scans were also evaluated to determine their usefulness in diagnosing osteomyelitis. Infected bone underlying pressure ulcers revealed only mild focal inflammatory changes which did not correlate well with x-ray and nuclear scan abnormalities. Negative scans, however, essentially ruled out osteomyelitis. There was no clear association of delayed healing or recurrence of pressure sore with osteomyelitis. Antibiotic therapy of greater than three weeks' duration did not significantly affect the outcome of the disease.

Persistence of polymicrobial abscesses in the poorly controlled diabetic host.

Polymicrobial infections are frequently found in soft tissue infections of the lower extremities in diabetic patients. The relative susceptibility to and persistence of soft tissue polymicrobial infections of diabetic and nondiabetic mice using bacteria commonly found in clinical foot infections were studied. Subcutaneous abscesses were induced in three groups of diabetic and nondiabetic mice using: (1) E. coli and enterococcus, (2) enterococcus and Bacteroides fragilis (B. fragilis), and (3) E. coli and B. fragilis. Abscesses were removed at 1 and 2 wk for total colony counts. At 1 wk, there was a significantly greater bacterial growth in the abscesses of the diabetic mice compared with the nondiabetic mice only in the group injected with enterococcus and B. fragilis. There were significantly higher colony counts in the diabetic compared with the nondiabetic mice in all three groups at 2 wk after injection of the bacteria. Two weeks after injection of inocula containing B. fragilis, both in combination with E. coli or enterococcus, all nondiabetic mice had eradicated B. fragilis from the abscesses, but significant numbers of B. fragilis persisted in the abscesses of the diabetic mice. In the diabetic mice, the presence of enterococci was more synergistic for growth of B. fragilis than was the presence of E. coli. These studies demonstrate that the bacteria of polymicrobial soft tissue infections persist for a longer period of time in the diabetic compared with the nondiabetic host. In addition, B. fragilis has increased pathogenicity in the diabetic compared with the nondiabetic host, particularly in the presence of enterococci.