Group A streptococci: localization in rabbits and guinea pigs following tissue injury.

Rabbits injected intravenously with extracellular products ("toxins") of group A streptococci develop myocardial, muscular, and hepatic lesions. When such animals are then challenged with fluorochrome-labeled group A streptococci or with titanium oxide particles the labeled bacteria or particles localize within phagocytic cells in the tissue lesions caused by the toxins. Similarly, labeled streptococci or titanium oxide particles will also localize within phagocytic cells in skin lesions of guinea pigs that develop delayed hypersensitivity to tuberculin or to bovine gamma globulin. It is proposed that a combined mechanism of injury and localization of bacteria in damaged tissues may be responsible for poststreptococcal sequelae or other chronic inflammatory diseases.

Pericarditis: differential diagnostic considerations.

A retrospective analysis of 133 patients was performed to define the factors identifying those individuals at risk for the more serious causes of pericardial disease. In 90% of the cases, the initial assessment from data obtained without pericardiocentesis or pericardiectomy proved correct. Underlying tuberculous or maligant pericarditis were the most common sources of error on initial assessment. Hemodynamic compromise exclusive of anticoagulants, roentgenographic cardiomegaly, pleural effusion, low voltage on ECG, and large pericardial effusion by echocardiography were more common (P less than .05) in tuberculous pericarditis than in acute idiopathic pericarditis. We discuss similar risk factors in patients with chronic idiopathic, rheumatologic, and uremic pericarditis. Anterior pericardiectomy is favored as the diagnostic procedure of choice in patients at risk for the more serious causes of pericarditis because of greater safety, diagnostic sensitivity, and potential therapeutic benefit.

Trimethoprim-sulfamethoxazole therapy for Nocardia infections.

The optimal therapy for infections due to Nocardia species has not been established. To assess the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX), we reviewed the records of 19 patients with Nocardia infections seen at Duke University Medical Center, Durham, NC, who were treated with this drug, either alone or in combination with other antibiotics or a surgical procedure. Underlying diseases or therapy causing immunosuppression were present in all but five cases. Sites of involvement were lung (ten of 19), wound (two of 19), and brain (two of 19); five of 19 patients had disseminated disease. The mean duration of therapy was 7.2 months. Overall cure or improvement was achieved in 89% (17/19) of cases; 80% of patients with disseminated disease and 60% of those with CNS involvement recovered. This experience, and accumulated clinical evidence in the literature, indicates that TMP-SMX should be considered the therapeutic drug of choice in infections due to Nocardia species.

Fungal infection following renal transplantation.

Twenty-seven deep fungal infections developed in 22 of 171 patients following renal transplantation. These infections included cryptococcosis (ten), nocardiosis (seven), candidiasis (four), aspergillosis (two), phycomycosis (two), chromomycosis (one), and subcutaneous infection with Phialophora gougeroti (one). Twelve infections occurred in living-related and ten in cadaveric recipients. Nineteen of the 22 patients were male. Infections occurred from 0 to 61 months after transplantation. Complicating non-fungal infections were present concomitantly in 15 patients. Thirteen patients died, eight probably as a result of fungal infection. Appropriate diagnostic procedures yielded a diagnosis in 20 of 27 infections, and therapy was begun in 18 patients. Serologic, culture, and biopsy procedures useful in making rapid diagnoses are advocated in the hope of increasing survival.

Short-course ciprofloxacin treatment of acute uncomplicated urinary tract infection in women. The minimum effective dose. The Urinary Tract Infection Study Group [corrected].

BACKGROUND: Three studies were undertaken to determine the minimum effective dosing regimen of ciprofloxacin for the treatment of acute, symptomatic, uncomplicated lower urinary tract infection. METHODS: All studies were multicenter, prospective, randomized, double-blind trials. A total of 970 evaluable patients with a diagnosis of urinary tract infection received oral ciprofloxacin (200 mg to 500 mg daily in one or two divided doses for 1, 3, 5, or 7 days) or norfloxacin (400 mg twice daily [BID] for 7 days). The primary measure of efficacy was bacteriologic eradication at the end of therapy. RESULTS: In study 1, bacteriologic eradication was reported in 95 (89%) and 101 (98%) of patients in the groups who received ciprofloxacin, 500-mg single dose and 250 mg BID for 7 days, respectively. Clinical success occurred in 101 patients (94%) who received a 500-mg single dose and in 103 patients (100%) who were administered 250 mg BID for 7 days. In study 2, eradication rates in the groups who received ciprofloxacin, 100 mg BID for 3 days, 250 mg BID for 3 days, and 250 mg BID for 7 days, were 98 (93%), 95 (90%), and 98 (93%), respectively. Clinical success was reported in 102 (97%), 105 (100%), and 104 (98%) of the patients, respectively. In study 3, the eradication rates in the groups who received ciprofloxacin in dosages of 500 mg once daily for 3 days and 500 mg once daily for 5 days and norfloxacin in a dosage of 400 mg BID for 7 days were 137 (92%), 134 (90%), and 133 (94%) of the women, respectively. Clinical success was the same (97%) in all three groups. Overall, short-course (either 3- or 5-day) therapy with ciprofloxacin was statistically equivalent to conventional (7-day) therapy with either ciprofloxacin or norfloxacin. Single-dose ciprofloxacin therapy was statistically less effective than conventional treatment. CONCLUSIONS: Ciprofloxacin at a dosage of 100 mg BID for 3 days was the minimum effective dose for the treatment of uncomplicated urinary tract infection in women.

Cryptococcemia.

Previous reports have emphasized that cryptococcemia is almost uniformly fatal. To define the clinical course and prognostic and therapeutic implications of cryptococcemia, we studied 15 patients treated at this medical center over the past 7 years. Cryptococcemia was strongly associated with corticosteroid therapy, especially when the dosage had recently been increased. Meningitis was common (but not invariably present) in these patients, characteristically with a large burden of organisms in the cerebrospinal fluid. Cryptococcemia developed during hospitalization in one-third of our patients; this high rate of nosocomial infection emphasizes that C. neoformans infection should be considered in febrile, immunocompromised patients even when the initial work-up is negative. Most of these patients were treated with amphotericin B plus 5-fluorocytosine. Although the one-year survival rate of 4/15 (29%) was dismal, no patient died from uncontrolled cryptococcal infection. Other infections, which developed before, during or after cryptococcemia was diagnosed, were the major immediate cause of morbidity and mortality. The progress of underlying diseases and the outcome of concomitant infections in these patients were more important determinants of survival than was cryptococcemia itself.

Single and multiple pyogenic liver abscesses. Natural history, diagnosis and treatment, with emphasis on percutaneous drainage.

The presenting features, modes of treatment and clinical course were reviewed for 55 patients with pyogenic liver abscess, seen at Duke University Medical Center over a 15-year period. Thirty-three patients had a solitary abscess and 22 had multiple abscesses. Most patients were between the ages of 40 and 60 years. Males predominated, 2.4:1. Major underlying conditions included biliary tract disease, malignancy and colonic disease. Eight patients, each with a solitary abscess, had no identifiable underlying condition. Symptoms and signs were nonspecific: fever, chills, focal abdominal tenderness and hepatomegaly were common. A raised serum alkaline phosphatase level was the most consistent abnormal laboratory finding. CT with contrast enhancement, radioisotope scanning and ultrasonography all accurately defined solitary hepatic abscesses. However, CT scan was more successful than other imaging techniques in detecting multiple abscesses. In seven patients the diagnosis was made only at laparotomy. Overall, a diagnosis of liver abscess was made in 50 living patients (91%). Microorganisms were recovered from pus and/or blood cultures of 44 patients (80%). Most common were enteric gram-negative facultative rods, anaerobic gram-negative rods, and microaerophilic streptococci. Single abscesses were more likely than multiple abscesses to contain more than one organism. All patients received antibiotics; the choice of antibiotic does not appear to be critical provided the regimen has a broad spectrum including activity against anaerobes. Surgical or percutaneous drainage was successful when attempted in all patients with a single abscess, but the outcome was less favorable in those with multiple abscesses. Percutaneous drainage is currently replacing open operative drainage as the method of choice. Overall mortality in patients with single abscesses was 15% (5/33) and in those with multiple abscesses 41% (9/22).

Staphylococcus aureus septicemia mimicking fulminant Rocky Mountain spotted fever.

Septicemia due to Staphylococcus aureus can be a difficult diagnosis to make early in its presentation. This report illustrates a case that mimicked fulminant Rocky Mountain spotted fever in a patient with no other medical problems that might predispose her to the development of staphylococcal sepsis. Epidemiology, cerebrospinal fluid characteristics, and early biopsy of skin lesions are emphasized as important factors leading to early diagnosis and definitive treatment.

Comparison of the safety and efficacy of intravenous ciprofloxacin and intravenous ceftazidime in the treatment of selected infections.

A study was conducted to determine the comparative safety and efficacy of intravenous ciprofloxacin with that of intravenous ceftazidime in the treatment of selected infections. Male and female inpatients 18 years or older had bacterial infections of the blood, skin or skin/structure, intra-abdominal region, lower respiratory tract, or urinary tract (considered complicated) caused by organisms susceptible to both ciprofloxacin and ceftazidime. Patients were randomly assigned to receive either ciprofloxacin 200 mg intravenously every 12 hours or ceftazidime 0.5 to 2 g intravenously every eight to 12 hours. Clinical evaluations were performed daily during therapy and within five to nine days after therapy was complete. For patients with urinary tract infection, urine for culture was obtained during (Day 3 or 4) and after (five to nine days and three to five weeks) therapy. A total of 86 patients were enrolled into the study. Forty-three received ciprofloxacin and 43 received ceftazidime. There were 22 evaluable patients in the ciprofloxacin group with 24 infection sites: skin/skin structure (eight), respiratory tract (nine), blood (two), urinary tract (five). In the ceftazidime group, there were 26 evaluable patients with 29 infection sites: skin/skin structure (15), respiratory tract (nine), blood (three), and urinary tract (two). The mean duration of therapy with ciprofloxacin and ceftazidime was 7.5 days (range, four to 28 days) and 8.4 days (range, three to 25 days), respectively. Bacteriologic eradication of the causative organisms occurred at 17 infection sites (70.8 percent) in the ciprofloxacin-treated patients and 21 infection sites (72.4 percent) in the ceftazidime group. Clinically, resolution or improvement in signs/symptoms was demonstrated in 22 patients (91.7 percent) in the ciprofloxacin group and 26 patients (89.7 percent) in the ceftazidime group. Bacteriologic response (by organism) and overall response were comparable in both groups. All enrolled patients were evaluated for determination of safety. Adverse events considered possibly or probably related to the study drugs were reported in 16 of 43 patients (37.2 percent) in the ciprofloxacin group and four of 43 patients (9.3 percent) in the ceftazidime group. Ciprofloxacin and ceftazidime were equally efficacious in the treatment of selected infections, but ciprofloxacin was associated with a higher incidence of adverse reactions probably or possibly related to drug administration. Further studies with larger sample sizes in selected patient populations will be required to identify differences in efficacy among the two antibiotics.

Comparative analysis of three antifungal susceptibility test methods against prospectively collected Candida species.

We performed antifungal susceptibility tests with cilofungin (LY121019), amphotericin B, and flucytosine against 38 strains of yeasts from patients with esophagitis or fungemia either before, during, or after treatment with cilofungin. Tests were performed using a macrobroth dilution method similar to that proposed by the National Committee for Clinical Laboratory Standards (M27-P) and two microbroth methods. For cilofungin and amphotericin B, minimum inhibitory concentrations from microbroth tests using Antibiotic Medium 3 (AM3) were systematically lower than results from the other two methods that utilized RPMI-1640 medium (RPMI). AM3 did not provide any greater degree of in vitro correlation with clinical results than did RPMI. We conclude that cilofungin and possibly other congeners of the echinocandin class of antifungal agents can effectively be studied using the proposed National Committee for Clinical Laboratory Standards method.

Azithromycin--spectrum of activity, pharmacokinetics, and clinical applications.

Azithromycin is an azalide antimicrobial agent. Structurally related to the macrolide antibiotic erythromycin, its mechanism of activity (similar to erythromycin) is interference with bacterial protein synthesis by binding to the 50S component of the 70S ribosomal subunit. Although slightly less potent than erythromycin against gram-positive organisms, azithromycin demonstrates superior activity in vitro against a wide variety of gram-negative bacilli, including Haemophilus influenzae. Absorption is approximately 37% after a 500-mg oral dose. The large volume of distribution (23 L/kg) and low peak serum level (0.4 micrograms/ml) are consistent with data demonstrating extensive tissue distribution and intracellular accumulation. Metabolism is predominantly hepatic (to inactive metabolites), with biliary excretion a major pathway of elimination. Drug elimination is biphasic, with a terminal half-life of up to 5 days. Published trials have examined the efficacy and safety of azithromycin in the treatment of adults with upper and lower respiratory tract infections, skin and skin structure infections, streptococcal pharyngitis, and sexually transmitted diseases. Many used a 5-day course of 250 mg once daily, supplemented with a 250-mg dose on the first day of therapy. Selected trials in sexually transmitted diseases examined single 1-g doses. Promising results also were obtained with oral daily doses of 500 mg in patients with human immunoviral infection who also had Mycobacterium avium complex infection and in animals with toxoplasmosis. Adverse reactions are primarily gastrointestinal (nausea, diarrhea, abdominal pain), with minimal laboratory abnormalities reported. Gastrointestinal tolerance is better than that of erythromycin. Drug interactions have not been observed to date, although coadministration of azithromycin with a large meal may reduce absorption by up to 50%.

Ofloxacin: its pharmacology, pharmacokinetics, and potential for clinical application.

Ofloxacin is a 4-quinolone antibiotic with rapid bactericidal activity against a wide variety of organisms. Its proposed mechanism of activity is interference with DNA gyrase, an enzyme essential for the replication of bacterial DNA. In vitro activity of ofloxacin includes a variety of aerobic and anaerobic bacteria. Enteric gram-negative bacilli and cocci are generally sensitive to ofloxacin; nonaeruginosa strains of Pseudomonas are less so. Numerous bacterial pathogens of the gastrointestinal tract are also sensitive to the drug. Although its MIC values for gram-positive aerobic organisms are generally higher, ofloxacin's bactericidal activity against these organisms is considered by some to be adequate, and superior to that of most other fluoroquinolones. Ofloxacin is well absorbed after oral administration. Wide tissue and body fluid distribution is demonstrated. Urinary excretion is thought to be the primary route of elimination, with 80% of the dose recovered in the urine within 24 hours. The serum half-life ranges between 2.9 and 9 hours in a dose-dependent manner. Only modest accumulation is reported after multiple-dose administration. Clinical trials using daily dosages of 100-800 mg/day in single or divided doses have been reported in the treatment of a variety of conditions such as skin and soft tissue infections, tonsillitis, sexually transmitted disease, respiratory tract infections, cystitis, and complicated and uncomplicated urinary tract infections. English reports of these trials, however, are generally limited to abstract form, making evaluation of trial design difficult. Side effects most frequently encountered include gastrointestinal and central nervous system reactions.

Postoperative intervertebral disc space infection.

Intervertebral disc space infection is an uncommon, but serious, complication of disc surgery. By a retrospective chart review, we identified 27 patients at our institution who had a postoperative disc space infection; 14 were diagnosed and treated within the last 5 years. The characteristic symptoms were severe spinal pain and limited spinal mobility beginning 7 to 30 days postoperatively. The key physical findings were paravertebral muscle spasm and marked mechanical signs. The key laboratory findings were an elevated erythrocyte sedimentation rate and a mildly elevated white blood cell count. The diagnosis was based on the clinical presentation and early radiographic changes in the vertebral bodies adjacent to the involved disc, especially irregularities of the cortical margins seen best by tomography. Definitive bacteriological diagnosis by Craig needle biopsy was attempted in 14 patients; 7 had positive cultures and all yielded a Staphylococcus species. The usual treatment consisted of the administration of antistaphylococcal antibiotics and immobilization of the spine with a spica cast, a plastic body jacket, or complete bedrest. The final radiographic findings showed bony fusion or bridging in 19 patients, and 25 patients had a pain-free recovery after 1 to 9 months. There was 1 recurrent infection, and 3 patients eventually required an anterior discectomy and fusion. Based on a review of our own cases and those reported in the literature, we stress the importance of spinal tomography in establishing the diagnosis of postoperative disc space infection at a relatively early stage in a patient who is suspected of having this condition on the basis of typical symptoms and signs combined with an elevated sedimentation rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Infections in elderly cancer patients.

In order to approach infections in elderly patients with cancer, one must have an understanding of infections in normal elderly populations. This article approaches infections in elderly patients by an examination of host factors, presentation of various organisms, infections of various body sites, diagnosis, treatment, and prevention.

Subacute staphylococcal pneumonia in a renal transplant recipient.

A patient is reported who developed subacute staphylococcal pneumonia 17 months after renal transplantation. Although the illness was modified by oral antimicrobial drugs, a remarkably benign course was observed, leading to a presumptive diagnosis of opportunistic fungal infection. Thus, staphylococcal pneumonia may complicate the differential diagnosis of pulmonary infection in transplant recipients.

The clinical spectrum of Nocardia brasiliensis infection in the United States.

Seven cases of infection due to Nocardia brasiliensis were identified over a 13-year period at Duke University Medical Center, Durham, North Carolina. These seven cases and a review of 55 cases in the literature reported from the United States show that N. brasiliensis can cause a wide spectrum of disease. Forty-six of the 62 patients had disease of skin and soft tissues. Cutaneous manifestations included cellulitis, pustules, ulcerations, pyoderma, subcutaneous abscesses, a lymphocutaneous syndrome, and mycetoma. Six patients had pleuropulmonary disease, and one patient had isolated central nervous system (CNS) involvement. Dissemination of disease, a characteristic generally attributed to Nocardia asteroides infection, was seen in eight instances. Patient ages ranged from one to 79 years; 51 of the patients were males. N. brasiliensis was an opportunistic pathogen in only 28% of the cases for which adequate clinical information was available, although trauma was an important predisposing feature of cutaneous disease (19 of 43 cases). Infection may be acquired either by cutaneous inoculation or respiratory inhalation. Clinical outcome is related to the site and extent of disease and to the presence or absence of serious underlying disease. All patients with skin and soft-tissue infections recovered, as did 83% of those with pulmonary involvement. For patients with disseminated or CNS disease, however, mortality was 67%. Traditional therapy with sulfonamides is not optimal for metastatic nocardial disease, and administration of trimethoprim-sulfamethoxazole may increase rates of cure.

Phycomycosis of the vulva.

A necrotic ulcerative lesion of the vulva in a patient with diabetic ketoacidosis initially resembled necrotizing fasciitis. Debridement and histologic examination led to a diagnosis of phycomycosis. The condition responded to surgical debridement without antifungal therapy.

Degradation of 14C-labeled streptococcal cell walls by egg white lysozyme and lysosomal enzymes.

The resistance of native and trypsin-treated [14C] glucose-labeled cell walls to degradation by lysozyme and human lysosomal enzymes was confirmed. In contrast, chemically N-acetylated cell walls undergo significant degradation by these enzymes in the pH range of 4.5 to 5.5 without prior removal of the group-specific carbohydrate. N-acetylation after removal of the group A carbohydrate by formamide extraction renders the cell walls considerably more susceptible to these enzymes than by formamaide extraction alone. It appears, therefore, that unless N-acetylation can occur in vivo, streptococcal cell walls are minimally degraded, if at all, by human peripheral blood leukocytes or lysozyme. Examination of leukocyte extracts from normal subjects and patients with post-streptococcal syndromes revealed no qualitative differences in ability to dissolve streptococcal cell walls.