In a retrospective study conducted in an Italian tertiary care hospital, the incidence of nosocomial candidemia was evaluated together with causative pathogens, treatment, and risk factors for death. Over a 6-year period (1992-1997), a total of 189 episodes of candidemia occurred in 189 patients (mean age 58+/-19 years), accounting for an average incidence of 1.14 episodes per 10,000 patient-days per year. The most common reasons for hospitalization were solid neoplasia (21%), trauma (17%), abdominal diseases requiring surgery (13%), and cardiovascular diseases (13%). No patient was neutropenic within 3 weeks prior to the onset of candidemia. One hundred thirty patients were hospitalized in intensive care units, 47 patients in surgical wards, and 12 patients in medical wards. Candida albicans was the most frequently isolated pathogen, accounting for 54% of fungal isolates, followed by Candida parapsilosis (23%), Candida glabrata (7%), Candida tropicalis (5%), Candida pelliculosa (4%), Candida lusitaniae (1%), Candida humicula (1%), and other non-albicans Candida spp. (5%). Seventy-six (41%) patients received adequate antifungal therapy. Seventy-one (58%) of the 123 evaluable patients with central venous catheters underwent line removal; 51 of them had catheter-related candidemia. The 30-day crude mortality rate was 45%. Older age, hospitalization in an intensive care unit, a longer duration of candidemia, retention of central lines, and inadequate antifungal therapy were significantly associated with poor outcome. In the present study, nosocomial candidemia was a frequent and relatively underestimated illness. Adequate antifungal therapy and central line removal independently reduced the high mortality of the disease.

Cryptococcus neoformans isolates that exhibited unusual patterns of resistance to fluconazole and voriconazole were isolated from seven isolates from two different geographical regions: one isolate from an Israeli non-AIDS patient and six serial isolates from an Italian AIDS patient who had suffered six recurrent episodes of cryptococcal meningitis. Each isolate produced cultures with heterogeneous compositions in which most of the cells were susceptible, but cells highly resistant to fluconazole (MICs, >64 g/ml) were recovered at a variable frequency (7 ؋ 10 ؊3 to 4.6 ؋ 10 ؊2 ). Evidence showed that this type of resistance is innate and is unrelated to drug exposure since the Israeli patient had never been treated with azoles or any other antimycotic agents. Analysis of clonal subpopulations of these two strains showed that they exhibited heterogeneous patterns of resistance. The number of subpopulations which grew on fluconazole or voriconazole agar declined progressively with increasing azole concentration without a sharp cutoff point. For the Italian serial isolates, the number of clonal populations resistant to fluconazole (64 g/ml) and voriconazole (1 g/ml) increased steadily, yielding the highest number for the isolate from the last episode. Attempts to purify a sensitive subpopulation failed, but clones highly resistant to fluconazole (100 g/ml) and moderately resistant to voriconazole (1 g/ml) always produced a homogeneous population of resistant cells. Upon maintenance on drug-free medium, however, the majority of the homogeneously resistant cells of these subclones lost their resistance and returned to the stable initial heteroresistant phenotype. The pattern of heteroresistance was not affected by the pH or osmolarity of the medium but was influenced by temperature. The resistance appeared to be suppressed at 35°C and was completely abolished at 40°C. Although heterogeneity in azole resistance among subpopulations of single isolates has been reported for Candida species, the transient changes in expression of resistance under different growth conditions reported here have not been observed in fungal pathogens.

Between September and October 1994 we observed three cases of Pseudomonas aeruginosa endophthalmitis in a single ophthalmology center. Endophthalmitis progressed rapidly following surgical intervention, and the three patients completely lost vision in the affected eye. Microbiological surveillance culture specimens were obtained from environmental sites, the operating team, intraocular lenses, irrigation fluids, and surgical equipment. P. aeruginosa was isolated from the internal tubing system of automated cataract surgical equipment. The strains of P. aeruginosa cultured from vitreous and anterior chamber specimens of case patients and from the surgical equipment were analyzed with pulsed-field gel electrophoresis. Genomic DNA typing of these isolates showed an identical banding pattern on ethidium bromide-stained gels. We believe that this is the first reported outbreak of P. aeruginosa endophthalmitis traced to automated surgical equipment. Genomic DNA typing emerged as a practical and reliable option for the epidemiological investigation of the outbreak.

Enterococci are characterized by an intrinsic resistance to growth inhibition by beta-lactam antibiotics. The low susceptibility of enterococci to beta-lactam antibiotics is associated with the synthesis of a particular penicillin-binding protein (PBP) that has a low affinity for beta-lactam agents. This protein appears to be capable of taking over the function of the other PBPs when they are saturated with beta-lactam molecules or inactivated by mutations. A quantitative correlation can be established between the binding of several beta-lactam molecules to the low-affinity PBP and the minimal inhibitory concentration for enterococcal strains. In contrast, the mechanism of enterococcal resistance to the bactericidal activity of beta-lactam agents that inhibit growth at relatively low concentrations appears to be associated with an alteration in the pattern of autolytic enzyme activity. In particular, lack of or poor activity of an autolytic enzyme appears to be responsible for the paradoxical bactericidal response often exhibited by clinical isolates of Enterococcus faecalis in the presence of penicillin.

A 73-year-old man developed an acute prosthetic aortic valve dehiscence for which emergent operation was undertaken. The intraoperative evidence of an aortic annular disruption and of a subannular abscess led to the hypothesis that an endocarditis process was involved. The aortic valve was replaced with a stentless porcine bioprosthesis. Cultures taken intraoperatively from the aortic area had a pure growth of aerobic, sporeforming, gram-positive bacilli identified as Bacillus licheniformis. The patient responded to specific antibiotic therapy with no relapse at a 20-month follow-up. The potentiality of B. licheniformis as a pathogen should be reconsidered.With the exception of Bacillus anthracis infections, serious infections caused by aerobic, spore-forming, gram-positive Bacillus species are rare (5). Only a few cases have been reported previously, and these have often occurred in conjunction with the host's immunological incompetence, associated with operative procedures, wounds and burns, hemodialysis, and food poisoning, and in a parenteral drug abuser (5,11). We describe here a unique case of life-threatening B. licheniformis endocarditis occurring on a prosthetic aortic valve, for which reoperation was successfully undertaken. To the best of our knowledge, this is the first reported case of endocarditis due to this etiology in an immunologically normal patient.A 73-year-old white male under medical treatment for arterial hypertension and type II diabetes was admitted to the University of Verona Medical School hospital with acute pulmonary edema. He had undergone 12 years before an aortic valve replacement (25-mm-diameter mechanical prosthesis; St. Jude Medical Inc., St. Paul, Minn.) in association with an epicardial pacemaker implantation (C2141; Vitatron Medical B.V., Dieren, The Netherlands) for the treatment of a calcified aortic valve with a complete atrio-ventricular block.On admission, the patient presented with dyspnea at rest and leg edema. His blood pressure was 100/45 mm Hg, and his body temperature was 37.4ЊC. The hematocrit was 40% with a hemoglobin level of 13.6 g/100 ml. The leukocyte count was 9,150/mm 3 with 86.9% neutrophils.The erythrocyte sedimentation rate and the C-reactive protein level were moderately elevated. A grade IV/VI blowing diastolic murmur was audible in the aortic area. A chest roentgenogram revealed a moderate cardiomegaly (cardiothoracic ratio, 0.6%) and evidence of severe pulmonary edema. Twodimensional transesophageal echocardiography showed severe aortic valve regurgitation due to an extensive periprosthetic leak associated with diminished left-ventricular function. Cardiac catheterization confirmed the diagnosis and revealed normal coronary arteries. The patient was then taken to the operating room, where, under general anesthesia and with total cardiopulmonary bypass, he underwent removal of the previously implanted artificial aortic valve, detached for about one-third of its circumference. After removal of the valve, a limited abscess was noted underneath the aort...

The ultrastructure of twenty human intestinal spirochetes was analyzed using the electron microscope. Negatively stained cells were generally found to be loosely and irregularly waved. The isolates had cell dimensions ranging from 0.18-0.35 micron in width and from 3.9-14.2 micron in length. Twin bundles of flagella were present in the space between the cytoplasmic membrane and the outer membrane. The majority of isolates had five flagella inserted sub-terminally at each cell end. Human intestinal spirochetes divide by binary fission. They are morphologically similar to swine intestinal treponemes, both pathogenic (Treponema hyodysenteriae) and non pathogenic (Treponema innocens), and different from Treponema pallidum, Treponema phagedenis and Borrelia burgdorferi. Following treatment with sodium deoxycolate, no bundles of cytoplasmic microtubules were observed in cells obtained from cultures of human and swine intestinal spirochetes or from cells of B. burgdorferi, while these structures were present in similarly treated cells of T. pallidum and T. phagedenis.

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