David K. Wagner

Effect of Bone Biopsy in Guiding Antimicrobial Therapy for Osteomyelitis Complicating Open Wounds

BackgroundOsteomyelitis associated with infected overlying wounds represents a difficult diagnostic and therapeutic problem; bone biopsies can be done during debridement of the overlying wounds, but it is unclear how often the results of these bone cultures actually affect subsequent antibiotic decisions. The present study was undertaken to evaluate the usefulness of bone biopsies in guiding antibiotic therapy for this type of osteomyelitis. MethodsCulture results of 44 bone biopsies taken during surgical debridement in 41 patients over the period from June 1994 to August 1998 were compared with those from the overlying wounds to determine whether the data affected the subsequent choice of antibiotics. The study design was that of a retrospective chart review in which the standard operative and microbiological procedures in place at the Milwaukee Veterans Affairs Medical Center were used. ResultsSixty-one wound and 55 bone isolates were obtained during this study. Thirty-one isolates were found in bone, but not the overlying wound; diphtheroids were the most common organism obtained in this fashion. Correlation between wound and bone isolates was generally poor. Antibiotics were subsequently changed in 20 of the 44 cases after results of the bone biopsy became known, with the bone isolates already being covered in 10 cases and the bone biopsy results ignored in 14 cases. ConclusionBecause bone biopsy results seem to aid in tailoring antibiotic therapy in almost half the cases when bone is sampled during wound debridement surgery, this technique may be very helpful in certain cases and should be regularly undertaken when these procedures are carried out.

Epidural abscess, vertebral destruction, and paraplegia caused by extending infection from an aspergilloma

An aspergilloma developed in a lung cyst in a 53-year-old man. Aspergillus infection then contiguously spread to the epidural space, causing an abscess, vertebral destruction, and paraplegia at the level of T4. Chronic alcoholism, liver cirrhosis, and corticosteroid treatment may have been predisposing factors in this patient. Although Aspergillus epidural abscess has been described infrequently, this complication has not been described in association with an aspergilloma. Symptoms, signs, or roentgenographic or laboratory findings suggestive of vertebral or meningeal pathologic lesions in patients with aspergilloma should alert the physician to the possibility of contiguous spread of infection.

Dysgonic fermenter 3-associated gastrointestinal disease in a patient with common variable hypogammaglobulinemia

A gram-negative bacteria designated DF-3 was cultured on multiple occasions from stool samples of a patient with common variable hypogammaglobulinemia and chronic diarrhea. Antibiotic therapy resulted in elimination of the organism and resolution of the patients symptoms. DF-3 has not been linked previously to human disease; because of its fastidious growth characteristics and unique isolation requirements, it may be a rarely identified cause of diarrhea and other gastrointestinal symptoms in immunocompromised patients.

Successful treatment of post-mitral valve annuloplasty aspergillus flavus endocarditis

Aspergillus endocarditis is associated with a very high mortality. Of approximately 67 cases reported in the English language literature, there have been only two known survivors. This report describes a patient with Aspergillus flavus endocarditis after mitral valve annuloplasty who recovered with combined surgical and antifungal therapy. This is the first successfully treated case due to A. flavus and the first involving an annuloplasty ring.

Comparison of the metal-binding anticandidal activities of serum and abscess fluid supernatants

Serum transferrin appears to play a role in host defense by competing with invading microorganisms for iron. The purpose of the present study was to compare this activity to a similar one recently described in abscess fluids and based on a calcium- and zinc-binding protein called calprotectin. Serum and abscess fluid supernatants were collected and pooled from groups of five to 10 C57BL/6 mice with experimental Candida albicans abscesses; serum was also collected from normal animals. In four experiments, serum was found to reduce in vitro C. albicans growth in Sabouraud glucose broth by a mean of 97.9% at 10 mg ml-1 of protein; this effect was reversed by adding 3-10 microM FeCl3, but not by similar amounts of ZnSO4. Abscess fluid supernatants had a greater effect, reducing growth by 99.9% at 1 mg ml-1 and 76.1% at 0.1 mg ml-1 of total protein; this effect was reversed by 3-10 microM ZnSO4, but not FeCl3. Although abscess fluid supernatants were effective when high inocula (10,000 yeast cells) were used, serum from the infected mice inhibited growth only with lower inocula (10-100 yeast cells). In a separate study, serum from infected mice (eight pools) reduced growth (by a range of 36 to 97%), whereas serum from normal mice (five pools) actually enhanced growth in this system (by a range of 173 to 595%).(ABSTRACT TRUNCATED AT 250 WORDS)

Release of soluble interleukin-2 receptors (Tac peptide) in vivo during human immune responses to tuberculin

Cutaneous levels of soluble interleukin-2 receptor (Tac peptide) have been measured in tuberculin responses in 13 human volunteers by assaying the fluid present in suction-induced blisters at various times after injection of standard purified protein derivative of tuberculin (PPD). Low levels of Tac peptide were found in blisters without prior injection of PPD and in PPD-negative individuals, and maximal levels of Tac peptide were correlated with increased induration at 48 hr (r = 0.69, P = 0.04) in PPD-positive subjects. This is the first report of measurement of Tac peptide in vivo in a defined immune response in man, and may offer a new approach to the study of human immune function in vivo.

Immunology of Cutaneous Candidiasis

Cutaneous candidiasis represents infections of the epidermis, primarily the stratum corneum of the skin, with C. albicans and occasionally certain non-C. albicans species. The condition known as chronic mucocutaneous candidiasis consists of a variety of syndromes with varying degrees of immune dysfunction and resulting chronic infections of the skin, nails, and mucous membranes with Candida organisms. The various forms of cutaneous candidiasis have a number of predispositions, such as warmth, moisture, and occlusion at the local site, various kinds of natural or iatrogenic immunosuppression, and perhaps some degree of inherited susceptibility. The immune system, particularly CMI, appears to be important in the defense against this type of infection. In the skin the mechanisms involved in generating immunologic reactions are particularly complex, with epidermal Langerhans cells, other dendritic cells, lymphocytes, microvascular endothelial cells, and the keratinocytes themselves all playing important roles. Studies of cutaneous candidiasis have elucidated a number of immunologic defects, which in some cases may be preexistent and in others may be secondary to the infection itself. Different mechanisms may cause immunologic dysfunction in individual patients and lead to the development of chronic infections. Although an inability to develop protective immune responses appears to be involved in the chronicity of certain cutaneous Candida infections, treatment at the present time depends primarily on antifungal medications; therapeutic modalities aimed at reversing the underlying immunologic defects remain experimental.

Arrays of Candida albicans pseudohyphae that protect the organisms from neutrophil fungicidal mechanisms in experimental infections of mice

Experimental subcutaneous Candida albicans infections in mice were used to examine the manner in which this pathogen is cleared in animals recovering from cyclophosphamide-induced leucopenia. In this system, infections at the inoculation sites progressed rapidly during a 6 day period of leucopenia to form arrays of parallel filamentous organisms that effectively isolated those in the interior from contact by neutrophils, even when the leucopenia had resolved. Dense collections of organisms also developed at sites of metastatic infection in the kidneys. A majority of the organisms were found to be viable when they were retrieved from the infected subcutaneous sites of animals that had recovered from leucopenia and whose abscesses had begun to drain spontaneously. Removal of the protective arrays of fungal cells appeared to be accomplished by drainage of abscess contents through the surface of the skin or into the collecting system of the kidney. Drainage of the subcutaneous abscesses did not occur in the cyclophosphamide-treated animals until after the neutrophilic infiltrates had developed, suggesting that this drainage process was mediated by neutrophils rather than by the organisms themselves. In summary, the above findings demonstrate that C. albicans infections in leucopenic hosts may progress to the extent that they would be very difficult to clear solely through the microbicidal processes of returning neutrophils. However, neutrophils also appear to promote the removal of masses of viable fungal cells to the exterior of the body.

Concentration of ciprofloxacin in bone tissue after single parenteral administration to patients older than 70 years

SummaryThe concentrations of ciprofloxacin produced in bone, cartilage and menisci after a single administration of 200 mg were determined at different intervals in a group of patients with an average age of 80 years. Concentrations of 0.11 to 0.94 mg/kg bone tissue were measured after 0.5 to 5 hours. In the cartilage a concentration of active substance was measurable only once (4.18 mg/kg). In the presence of marked circulatory disorders the active substance concentrations reached in the bone were above those found in the seriously damaged muscle. Although the concentrations reached in the bone are effective, no risk should be taken in osteomyelitis. Ciprofloxacin should therefore be used at high dosage and possibly be combined with another substance. Given for therapeutic purposes, a single dose of ciprofloxacin is naturally not effective enough, and given for prophylactic purposes, not safe enough to prevent a post-traumatic osteitis.ZusammenfassungBei einem Patientenkollektiv mit einem Durchschnittsalter von 80 Jahren wurden Knochen, Knorpel und Menisci auf ihren Gehalt von Ciprofloxacin nach Einmalgabe von 200 mg der Substanz nach unterschiedlichen Zeitspannen untersucht. Im Knochen wurden nach einer Zeitdauer von 0,5 bis 5 Stunden 0,11 bis 0,94 mg/kg Gewebe gemessen. In Knorpel fand nur einmal eine Anreicherung statt (4,18 mg/kg). Bei erheblichen Durchblutungsstörungen lagen die Substanzspiegel der Knochen über denen der schwer geschädigten Muskulatur. Die Werte zeigen zwar effektive Knochenspiegel, dennoch sollte bei der Osteomyelitis kein Risiko eingegangen werden und Ciprofloxacin höher dosiert und eventuell mit einer anderen Substanz kombiniert werden. Eine Einmalgabe ist natürlich als Therapiedauer zu kurz, als Prophylaxe zur Verhinderung einer posttraumatischen Osteitis zu unsicher.

Cellular source of soluble interleukin 2 receptors in serum of mice after recombinant interleukin 2 administration

Previous studies have shown that peripheral blood mononuclear cells activated in vitro not only express cell-associated interleukin 2 receptors (IL2R) but also release a soluble form of this receptor. In this study, we demonstrate that administration of human recombinant IL 2 (rIL 2) to mice results in increased spleen weights, splenic natural killer (NK) cell cytolytic activity, and serum levels of soluble IL2R. However, compared with rIL 2-treated heterozygote controls, beige mice treated with rIL 2 displayed similar elevations in serum soluble IL2R but significantly less splenic NK activity. Likewise, administration of anti-asialo GM1 antiserum to rIL 2-treated mice resulted in a dramatic reduction in splenic NK cytolytic activity, but no reduction in serum soluble IL2R. Conversely, while rIL 2 treatment of BALB/c mice produced increased splenic NK activity and serum soluble IL2R, similar treatment of BALB/c nude mice resulted in elevation of only splenic NK activity. These studies demonstrate that administration of rIL 2 to normal mice can elevate both serum IL2R levels and splenic NK cytolytic activity. However, the results suggest that T cells are likely to be the source of elevated serum IL2R after rIL 2 administration.