Brian E. Scully

An outbreak of Legionella micdadei pneumonia in transplant patients: evaluation, molecular epidemiology, and control

PURPOSE To describe a nosocomial outbreak of Legionella micdadei pneumonia in transplant patients and to characterize the source of the outbreak and the control measures utilized. SUBJECTS AND METHODS We performed retrospective Legionella micdadei serologic testing to enhance case finding in transplant patients with pneumonia that lacked a documented microbial etiology, as well as prospective environmental surveillance of water sites and testing for Legionella in clinical specimens. RESULTS During a 3-month period, 12 cases of Legionella micdadei pneumonia were identified either by culture or serologic testing among 38 renal and cardiac transplant patients. Legionella micdadei isolates from hot water sources were found by pulsed-field gel electrophoresis to have a DNA banding pattern that was identical to the isolates from the first 3 culture-positive cases and from 2 cases that occurred 16 months later. CONCLUSIONS Hospitals caring for organ transplant recipients and other immunosuppressed patients must be aware of the possibility of environmental sources of outbreaks of Legionella infection. A first-line screen with the Legionella urine antigen test will identify Legionella pneumophila serogroup 1. However, specific cultures in outbreak situations should be considered to identify other Legionella pneumophila serotypes and the nonpneumophila Legionella species.

Cardiac transplantation using extended-donor criteria organs for systemic amyloidosis complicated by heart failure.

Background. Systemic amyloidosis complicated by heart failure is associated with high cardiovascular morbidity and mortality. Heart transplantation for patients with systemic amyloidosis is controversial due to recurrence of disease in the transplanted organ or progression of disease in other organs. Methods. All patients with systemic amyloidosis and heart failure referred for heart transplant evaluation from 1997 to 2004 were included in this retrospective cohort analysis. An interdisciplinary protocol for cardiac transplantation using extended-donor criteria organs, followed in 6 months by either high-dose chemotherapy and stem cell transplantation for patients with primary (AL) or by orthotopic liver transplantation for familial (ATTR) amyloidosis, was developed. Survival of the transplanted amyloid cohort was compared to survival of those amyloid patients not transplanted and to patients transplanted for other indications. Results. A total of 25 patients with systemic amyloidosis and heart failure were included in the study; 12 patients received heart transplants. Amyloid heart transplant recipients were more likely female (58% vs. 8%, P=0.02) and had lower serum creatinine (1.3±0.5 vs. 2.0±0.7 mg/dL, P=0.01) than nontransplanted amyloid patients. Survival at 1-year after heart transplant evaluation was higher among transplanted patients (75% vs. 23%) compared to patients not transplanted (P=0.001). Short-term survival posttransplant did not differ between transplanted amyloid patients and contemporaneous standard and extended-donor criteria heart transplant patients (P=0.65). Conclusions. Cardiac transplantation for amyloid patients with extended-donor criteria organs followed by either stem cell or liver transplantation is associated with improved survival compared to patients not transplanted. Short- to intermediate-term survival is similar to patients receiving heart transplantation for other indications. This clinical management strategy provides cardiac amyloid patients a novel therapeutic option.

Streptococcus agalactiae (group B) endocarditis — A description of twelve cases and review of the literature

SummaryThe group B streptococcus has been shown to be a major cause of meningitis in the newborn and an occasional cause of endocarditis and sepsis in postpartum women. Little attention has been devoted to this organism as a cause of bacterial endocarditis. Twelve patients with group B streptococcal endocarditis were seen at The Presbyterian Hospital, New York, NY, between 1974 and 1985. There were seven women, five men. Ages ranged from 32 to 81 years. Serious underlying disease was present in all — diabetes mellitus in seven, carcinoma in three (bladder in two, and breast in one), alcoholism in three, malnutrition in two, heroin addiction in one, tuberculosis in one, serious prior valvular heart disease in two. The aortic valve was affected in four patients — mitral in two, mitral and aortic in one, tricuspid in four, unknown in one. The presentation was acute in seven patients. Metastatic infection occurred in seven, heart failure in six, major emboli in four, septic pericarditis in one, myocardial abscess in one. The group B streptococcus should be considered as a pathogen capable of causing acute endocarditis in certain patients with defects of host defense, particularly patients with diabetes mellitus, carcinoma or alcoholism. Cardiac surgery may be necessary in these patients due to the rapid destruction of the valves which occurs, in spite of the fact that the organisms are usually highly susceptible to penicillin.ZusammenfassungStreptokokken der Gruppe B haben sich als wichtige Erreger der Neugeborenenmeningitis erwiesen; gelegentlich lösen sie bei Frauen im Wochenbett eine Endokarditis oder Sepsis aus. Die Bedeutung dieses Mikroorganismus als kausaler Erreger der bakteriellen Endokarditis wurde bisher wenig beachtet. Am Presbyterian Hospital New York, NY, wurden zwischen 1974 und 1985 12 Fälle von Endokarditis durch Streptokokken der Gruppe B beobachtet, sieben Frauen und fünf Männer im Alter von 32 bis 81 Jahren. Bei allen Patienten bestand eine schwere Grundkrankheit, bei sieben ein Diabetes mellitus, bei drei ein Karzinom (zweimal Blasenkarzinom, einmal Mammakarzinom), bei drei Alkoholismus, bei zwei Malnutrition, bei einem Heroin-Sucht, bei einem Tuberkulose, und zwei Patienten hatten früher eine ernsthafte Herzklappenerkrankung durchgemacht. Die Endokarditis spielte sich bei vier Patienten an der Aortenklappe ab, bei zwei war die Mitralklappe, bei einem die Mitral- und Aortenklappe und bei vier die Trikuspidalklappe betroffen; in einem Fall war die Lokalisation unbekannt. Bei sieben Patienten bestand ein akutes Krankheitsbild. In sieben Fällen traten metastatische Infektionen auf, in sechs Fällen Herzversagen, bei vier Patienten kam es zu größeren Embolien, bei einem zur septischen Perikarditis und bei einem zu einem Myokardabszeß. Es sollte daran gedacht werden, daß B-Streptokokken bei bestimmten Patienten mit Abwehrschwäche, insbesondere bei Diabetes mellitus, Krebs oder Alkoholismus, eine akute Endokarditis auslösen können. Trotz der in der Regel hohen Empfindlichkeit gegen Penicillin führt die Infektion mit diesem Erreger rasch zur Klappenzerstörung; daher kann bei diesen Patienten ein herzchirurgischer Eingriff nötig werden.

The pharmacokinetic and bactericidal characteristics of oral cefixime

The pharmacokinetics of cefixime (FK 027), a broad‐spectrum cephalosporin, were assessed in 12 normal subjects after single oral doses of 50, 100, 200, and 400 mg. Mean peak serum concentrations were 1.02, 1.46, 2.63, and 3.85 µg/ml after the four respective doses. Respective mean serum levels at 12 hours were 0.16, 0.33, 0.72, and 1.13 µg/ml. Volumes of distribution averaged 0.1 L/kg body weight, and the elimination t½ was 3 hours for all doses. The AUC was 7.01, 11.4, 22.5, and 36.4 µg · hr/ml for the four doses, respectively. Serum clearance averaged 0.4 mg/min/kg and mean 24‐hour urinary recovery was 21%, 19%, 20%, and 16% for the four respective doses. Serum bactericidal titers at 4 hours exceeded 1:16 for Streptococcus pneumoniae, S. pyogenes, Hemophilus influenzae, and Branhamella catarrhalis. Urine bactericidal titers exceeded 1:8 for Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae resistant to the available oral cephalosporins.

Transfusion-associated babesiosis after heart transplant.

We describe a 54-year-old spleen-intact man with transfusion-associated Babesia microti infection after a heart transplant. Adult respiratory distress syndrome developed in the patient, and he required mechanical ventilation. Our experiences with this patient suggest that babesiosis should be considered in the differential diagnosis of transplant patients who have fever and hemolytic anemia.

The Pharmacokinetics and Serum and Urine Bactericidal Activity of Ciprofloxacin

Ciprofloxacin is an investigational quinolone agent possessing an impressive antibacterial spectrum. Its pharmacokinetics were studied in six volunteers after 250‐mg and 500‐mg single oral doses, and its bactericidal activity compared to that of trimethoprim‐sulfamethoxazole given to the same volunteers. Mean peak serum levels were 1.45 μg/mL and 2.46 μg/mL for 250‐mg and 500‐mg doses, and time to peak was 1 and 1.3 hours. The 12‐hour levels were 0.12 μg and 0.22 μg. Half‐life (T1/2)α were 0.32 and 0.43 with T1/2β were 3.97 and 4.15 and volume of distribution (area) were 80L and 90L, respectively. Area under the concentration curve (AUC) was 5.65 h · μg/mL and 10.37h · μg/mL. Serum clearance was 23L for both doses. Approximately 49% of the 250‐mg dose and 43% of the 500‐mg dose was recovered in the urine. Bactericidal levels were determined against clinical isolates. Sera at 1.5 hours after the 500‐mg dose averaged bactericidal levels of 1:20 or better for an Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa,and beta‐lactamase producing Haemophilus influenzae and Branhamella catarrhalis. Urinary bactericidal levels at eight to 12 hours were 1:157 for E coli, K pneumoniae, gentamicin‐piperacillin resistant P aeruginosa, Staphylococcus aureus, and 1:20 for Streptococcus faecalis. Serum bactericidal levels were superior, and urine bactericidal levels were superior or equal to the bactericidal levels obtained with trimethoprim‐sulfamethoxazole. Ciprofloxacins in vitro activity and human pharmacology should permit a twice or once daily dosing schedule for system 1C infections due to most Enterobacteriaceae, Haemophilus, Branhamella and Pseudomonas, and S aureus, and once daily for urinary gastrointestinal infections.

Use of aztreonam in the treatment of serious infections due to multiresistant gram-negative organisms, including Pseudomonas aeruginosa

Aztreonam is a novel antimicrobial agent belonging to the monobactam class of antibiotics. It inhibits both beta-lactamase-producing and non-beta-lactamase-producing aerobic gram-negative bacilli, but it has no activity against gram-positive species or against anaerobic species. The efficacy of aztreonam in the treatment of infection in 76 patients and its safety in 87 patients was evaluated. The majority (91 percent) of patients had significant underlying disease, and 47 percent were critically ill. Aztreonam produced an overall clinical response of 86 percent, with 10 of 11 cases of bacteremia cured, including four due to Pseudomonas aeruginosa, seven of eight cases of pneumonia, and seven of nine episodes of osteomyelitis. Infections due to bacteria resistant to ampicillin, carbenicillin, cefazolin, cefamandole, cefoxitin, and gentamicin were cured. Although 15 of 18 patients with exacerbations of pulmonary infection due to P. aeruginosa showed clinical improvement, bacteriologic cure was not achieved, as has been noted with other drugs. Similarly, patients with major underlying structural abnormalities of the urinary tract showed early relapses of bacteriuria. Aztreonam combined with antistaphylococcal, antistreptococcal, or antianaerobic agents provided an alternative to aminoglycoside use in these non-neutropenic patients. Administration of 1 or 2 g every eight hours yield serum bactericidal levels well in excess of 1:8 against all Enterobacteriaceae and some P. aeruginosa strains. There was a low incidence of adverse side effects, none serious. Overall, aztreonam is a useful alternative to the drugs available for use in hospital-acquired gram-negative infections and provides a chance for more directed therapy.

Mycobacterium avium complex infection in kidney transplant patients

Abstract: Mycobacterium avium complex (MAC) infections have been reported rarely in renal transplant patients. Consequently the clinical course and optimal treatment of these patients are not well understood. We present 3 patients with MAC infections after receiving a renal transplant (2 with generalized and 1 with localized infection). All patients were treated with combination antibiotic therapy and reduction of immunosuppression. One patient experienced clinical control of disease but a mild cellular rejection that was successfully treated with high‐dose corticosteroids. One patient died of disseminated MAC infection. The patient with localized infection died of unrelated causes. In summary, MAC infection, although rare in renal transplant patients, may respond to combination antimicrobial therapy and reduction of immunosuppression.

Five cases of bacteraemia due to Gordonia species

Gordonia species are aerobic Gram-positive bacilli and a rare cause of human disease. To our knowledge, there are only two cases of human infection with Gordonia sputi reported in the literature. We report five cases of bacteraemia due to Gordonia species at our institution since 2005, including four caused by G. sputi. Three of these cases were likely related to chronic indwelling central venous catheters.

Pharmacology of ticarcillin combined with clavulanic acid in humans

Serum and urine levels of ticarcillin and clavulanic acid after administration of doses of 50 mg/kg and 1.7 mg/kg or 50 mg/kg and 3 g/0.1 g, respectively, are potentially toxic to susceptible bacteria. Both compounds are widely distributed in body tissues and fluids, with concentrations exceeding the minimal inhibitory concentrations of most pathogens. Excretion is primarily renal, although there is some metabolism of clavulanate in the body. Due to accumulation, dosage adjustment is required for patients with renal insufficiency. Both ticarcillin and clavulanic acid are cleared by hemodialysis.