Molecular epidemiology of a clonal outbreak of multidrug-resistant Acinetobacter baumannii in a university hospital in Italy.

This study investigated the molecular epidemiology of a clonal outbreak of multidrug-resistant Acinetobacter baumannii that occurred between June 2003 and June 2004 in a tertiary-care hospital in Naples, Italy. A. baumannii was isolated from 74 patients, of whom 38 were infected and 36 were colonised. Thirty-three patients had ventilator-associated pneumonia, three had hospital-acquired pneumonia, and two had sepsis. Genotypic analysis of 45 available A. baumannii isolates revealed two distinct pulsed-field gel electrophoresis (PFGE) patterns. Of these, PFGE pattern 1 was represented by isolates from 44 patients and was identical to that of an epidemic A. baumannii clone isolated in another hospital of Naples during 2002. All A. baumannii isolates of PFGE type 1 showed identical multiresistant antibiotypes, characterised by resistance to all antimicrobial agents tested, including carbapenems, with the exception of colistin. In these isolates, inhibition of OXA enzymes by 200 mM NaCl reduced the imipenem MIC by up to four-fold. Molecular analysis of antimicrobial resistance genes showed that all A. baumannii isolates of PFGE type 1 harboured a class 1 integron containing the aacA4, orfX and bla(OXA-20) gene cassettes, an ampC gene and a bla(OXA-51)-like allele. Moreover, a bla(OXA-58)-like gene surrounded by the regulatory elements ISAba2 and ISAba3 was identified in a 30-kb plasmid from A. baumannii isolates of PFGE type 1, but not PFGE type 2. Thus, selection of a single A. baumannii clone producing an OXA-58-type carbapenem-hydrolysing oxacillinase was responsible for the increase in the number of A. baumannii infections that occurred in this hospital.

Efficacy and limitations of preemptive therapy against cytomegalovirus infections in heart transplant patients.

OBJECTIVES: Cytomegalovirus (CMV) disease often represents a serious complication that promotes opportunistic infections in heart transplant recipients. In this study we evaluated the impact of preemptive gancylovir therapy, guided by pp65 antigenemia on the morbidity associated with viral reactivation. PATIENTS AND METHODS: We have performed a CMV infection surveillance program since March 1999, with antigenemia pp65 determinations weekly for the first 2 months biweekly in the third months, and monthly to the sixth month. Patients with pp65 antigenemia value >/= 10 positive cells per 2 x 10(5) polymorphonuclear cells (PMN) were treated with intravenous gancyclovir followed by 1 month of oral gancyclovir. RESULTS: Among the 107 patients who underwent the virological monitoring, 80 were pp65 antigenemia-positive with preemptive therapy administered in 48 cases. Five patients displayed symptomatic CMV disease (4.7% vs 18% rate in the period of 1988 to 1998 before the introduction of virologic monitoring; P <.01). We observed only one case of gancyclovir-resistant pneumonia which was successfully treated with foscarnet. CMV recurrence in 10 patients required a second cycle of gancyclovir treatment. Our experience included 13 opportunistic infections (12.7%) with 11 antigenemia-positive. CONCLUSIONS: Preemptive therapy drastically reduces the incidence of CMV disease and the associated morbidity. Compared to universal prophylaxis, this approach may avoid unnecessary pharmacologic treatment in more than 50% of transplant recipients. Indeed, preemptive therapy does not fully prevent CMV disease, because it may manifest at the first antigenemia determination, and furthermore may select gancyclovir-resistant strains.

Midterm results of a prospective randomized comparison of two different rabbit-antithymocyte globulin induction therapies after heart transplantation.

This prospective randomized study compared the effects in heart transplant recipients of thymoglobulin and ATG, two rabbit polyclonal antithymocyte antibodies available for induction therapy. Among 40 patients (29 men and 11 women, mean age: 40.7 +/- 14 years) undergoing orthotopic heart transplantation, 20 were randomly allocated to receive induction with thymoglobulin (group A) and 20 to ATG-fresenius (group B). Comparisons between the two groups included early posttransplant (6 months) incidence of acute rejection episodes (grade >/= 1B), bouts of steroid-resistant rejection, time to first rejection, survival, graft atherosclerosis, infections, and malignancies. The study groups displayed similar preoperative and demographic variables. No significant difference was found with regard to actuarial survival (P =.98), freedom from rejection (P =.68), number of early rejections > 1B (P =.67), mean time to first early cardiac rejection (P =.13), number of steroid-resistant rejections (P =.69). Cytomegalovirus reactivations were more frequent among group A (65%) than group B (30%; P =.028). New infections due to cytomegalovirus occurred only in group A (four patients; 20%; P =.05). No cases of malignancies were observed at a mean follow-up of 32.8 +/- 8.9 months. Although thymoglobulin and ATG showed equivalent efficacy for rejection prevention, they have different immunological properties. In particular, thymoglobulin seems to be associated with a significantly higher incidence of cytomegalovirus disease/reactivation.

Heart transplantation during active infective endocarditis: case report and review of the literature.

Bacterial infections are a contraindication to organ transplantation, but infective endocarditis may require heart transplantation when otherwise untreatable. We describe a heart transplant patient with cardiomyopathy and ongoing defibrillator endocarditis due to Staphylococcus epidermidis. An initial attempt at percutaneous extraction of the 5 implanted leads was unable to eradicate the infection and was complicated by severe decompensation, requiring a new implant for biventricular pacing. Despite continuing bactericidal treatment, the patient showed persistent infection on the implanted leads with further hemodynamic deterioration. The decision was therefore made to list the patient for heart transplantation. The procedure was successful in removing all of the hardware. No recurrence of infection was observed despite persistence of large vegetations on the removed defibrillator leads. The patient had an uneventful postoperative course, remaining free of symptoms with negative blood cultures at 3 months' follow-up. Our experience showed that active infection of defibrillator leads may not represent an absolute contraindication to heart transplantation when all other medical and surgical treatments have been proven to be ineffective.

Hepatic cryptococcosis in a heart transplant recipient.

Cryptococcosis primarily occurs in patients with impaired immune response. While pulmonary and/or cerebral involvement are more often described, there is limited experience of its presence in other sites. We present a case of hepatic cryptococcosis with possible pulmonary involvement in a 54-year-old male heart transplant recipient. Two months after heart transplantation, he developed a persistent, moderate dyspnea with fever and signs of liver damage. Diagnosis was made with liver biopsy for a concurrent reactivation of chronic hepatitis B virus (HBV) infection already present before transplant. Along with a mild chronic HBV hepatitis with fibrosis, we observed sinusoidal dilation and groups of bright, rounded, colorless cells with a central nucleus suggestive of cryptococci. Periodic acid-Schiff stain clearly showed encapsulated yeasts, which supported the diagnosis. Cryptococcal antigen was positive in serum and negative in the cerebrospinal fluid. Computed tomography scan of the chest demonstrated a mild interstitial infiltrate. The patient promptly responded to reduction of immunosuppressive therapy and antifungal treatment with amphotericin B lipid complex and flucytosine followed by maintenance treatment with fluconazole. Cryptococcosis should always be considered in the differential diagnosis in immunocompromised hosts with dyspnea and signs of extrapulmonary involvement. Diagnosis of extrapulmonary and extraneural cryptococcosis is difficult and often fortuitous; a histopathological examination of tissues involved is probably warranted.

Treatment of pulmonary nocardiosis in heart-transplant patients: importance of susceptibility studies.

Pulmonary nocardiosis is an infrequent but insidious disease in transplant patients. It has occurred in our centre in 3 out of 233 heart-transplant recipients since 1988. Common clinical features were mild symptoms and a severe nodular lung involvement. Early diagnosis was based upon cultures of bronchoalveolar lavage or fine-needle aspirate specimens of the lung lesions. Susceptibility studies and tests of antibiotic synergism guided the therapy. Two patients were treated with a combination of piperacillin-tazobactam and ciprofloxacin, and one with imipenem and amikacin, for 3-4 wk followed by a 3-month course of trimethoprim-sulphamethoxazole. The nocardial disease was successfully treated in the 3 patients; however, one died of subsequent invasive pulmonary aspergillosis. In the absence of consensus on the length of therapy, this experience suggests that a synergistic combination of a beta-lactam/beta-lactamase inhibitor with ciprofloxacin or amikacin followed by a short course of trimethoprim-sulphamethoxazole may be effective in eradicating nocardial disease and may reduce the need for long-term treatment.