Stuart Levin

INFECTIOUS COMPLICATIONS OF SOLID ORGAN TRANSPLANTATIONS

The rate of infectious complications in SOT recipients has declined dramatically. As improvements in immunosuppressive therapy, surgical techniques, and diagnostics and antimicrobial treatment continue, further declines in infectious complications are expected. Refinements to preemptive therapy for high-risk patients are likely to contribute further to this decrease. Further investigation is required to define what role various infectious agents play in chronic allograft injury and rejection.

Pseudomonas maltophilia pseudosepticemia

During a 17 month period, 25 hospitalized adult patients had blood cultures reported as positive for Pseudomonas maltophila. Review of the hospital records suggested that these were contaminants and that blood for coagulation studies and for cultures that were subsequently positive had been drawn simultaneously. The source of contamination appeared to be black-top evacuated collection tubes used for coagulation studies in adults. Cultures of the liquid anticoagulant tubes yielded a pure growth of greater than 10(5) colony forming units (CFU)/cc of Ps. maltophilia on blood agar. Mock trials demonstrated that following venipuncture by syringe, inoculation of contaminated black-top tubes prior to inoculation of blood culture bottles would yield false-positive blood cultures (pseudosepticemia). One patient being treated for streptococcal prosthetic valve endocarditis and having frequent coagulation studies with blood obtained via direct venipuncture into evacuated collection tubes was found to have superinfection of his prosthetic valve with Ps. maltophilia at autopsy. Prosthetic valve infection may have occurred after reflux of contaminated anticoagulant from an evacuated collection tube directly into the vein. Contaminated evacuated collection tubes are a potential source of confusion in the diagnosis of infection as well as a potential source of true infection.

Antibodies to hepatitis B surface antigen as the sole hepatitis B marker in hospital personnel.

The epidemiologic and serologic differences between hospital employees with antibodies to hepatitis B surface antigen (anti-HBs) alone or in combination with antibodies to hepatitis B core antigen (anti-HBc) were evaluated. Of 105 employees with anti-HBs, 38 (36%) did not have anti-HBc. Sera from employees with anti-HBs alone had significantly lower mean sample ratio units of anti-HBs than sera with both antibodies (15.9 +/- 43.2 as compared to 110.3 +/- 73.9, p less than 0.0005) and more commonly had less than 10 sample ratio units of anti-HBs (32 [84%] of 38 as compared to 9 [13%] of 67, p = 0.0001). The anti-HBs in sera with anti-HBs alone was predominantly IgM as shown by inactivation with 2-mercaptoethanol and the presence of anti-HBs activity in serum IgM fractions. Failure of protection from hepatitis B virus infection in persons with anti-HBs alone and the presence of nonprotective IgM anti-HBs in chimpanzees has been reported. Our data suggest the use of anti-HBs as a single serologic screening test for hepatitis B virus immunization programs may not be reliable in identifying employees with protective antibodies.

Randomized study of intravenous/oral ciprofloxacin versus ceftazidime in the treatment of hospital and nursing home patients with lower respiratory tract infections

This study determined the efficacy of intravenous ciprofloxacin in the treatment of institutionalized patients with lower respiratory tract infections. Hospitalized adults with hospital/nursing home-acquired pneumonia were randomly assigned to receive either intravenous ciprofloxacin or ceftazidime. When deemed feasible, therapy was changed to oral ciprofloxacin for patients who received ciprofloxacin intravenously or to any alternative oral therapy for patients who received ceftazidime. All 23 patients who received ciprofloxacin had a favorable response versus 15 of 21 patients who received ceftazidime (p less than 0.025). One patient with a favorable response to ceftazidime developed a superinfection and one patient had a relapse during subsequent alternative oral therapy. However, patients who received ceftazidime were more severely ill than those who received ciprofloxacin on the basis of APACHE II scores.

The role of adenoviruses in the pertussis syndrome

To define the role of adenoviruses in the pertussis syndrome, a study was done of a group of 134 children with clinical pertussis and a healthy control population of similar age, race, sex, and socioeconomic status. Adenovirus infections occurred in 30 (22.4%) of 134 patients with the pertussis syndrome and 5 (4.9%) of 101 control subjects (p smaller than 0.001). B. pertussis was recovered from 46 (34.3%) patients, and from 18 (39.1%) of these patients adenoviruses were also isolated. Although adenovirus infections also occurred in patients with the pertussis syndrome with negative cultures for B. pertussis, the rate, 12 of 88 patients (13.6%), was significantly lower (p smaller than 0.001). The clinical course was similar irrespective of the results of bacterial or viral cultures. These data substantiate the frequent association of adenoviruses with the pertussis syndrome, It would appear that adenoviruses do not usually have an independent role in the pathogenesis of the pertussis syndrome since we found them so commonly to be one agent in a mixed infection.

Pneumococcal meningitis: the problem of the unseen cerebrospinal fluid leak.

A study was done of all patients treated for pneumococcal meningitis at the Municipal Contagious Disease Hospital, Chicago, Illinois, between 1954 and 1968 to estimate the frequency and differential features of recurrent diseases. Seventeen of 155 patients (11 per cent) had more than one episode of bacterial meningitis. There were 26 deaths in the non-recurrent and none in the recurrent group. Neurological complications occurred in five of 17 patients (29.4 per cent) with recurrent disease and 18 of 138 patients (12.9 per cent) without recurrent meningitis. Recurrent meningitis was more frequent in younger persons and males. Patients with recurrent disease were more likely to have an upper respiratory infection, to be hospitalized early in their illness, and to have positive blood cultures. Although a history of severe head trauma was significantly more frequent in those with recurrent disease (35.3 per cent) than in those without recurrences (9.4 per cent), this history was often overlooked by the patient even in the presence of cerebrospinal fluid rhinorrhea. Most often the trauma occurred six months or more prior to the initial episode of meningitis. The data suggest that each patient presenting with pneumococcal meningitis should be evaluated for evidence of dural tears or other host defense defects. Controlled data concerning surgical or antibiotic prophylaxis are needed.

Treatment of pertussis with pertussis immune globulin

Children with pertussis were treated with 2.5 c.c. of pertussis immune globulin or placebo in double-blind fashion. Patients were generally in the first week of the paroxysmal stage, and treatment and control groups were comparable. All children received ampicillin for 10 days. No difference in the rate of recovery between treated and control groups was noted with respect to the frequency of paroxysms of coughing, whooping, episodes of vomiting and suctioning required and pulmonary complications. These results are consistent with those of the few controlled studies in the literature, namely, that pertussis immune globulin is of no value in treatment at this stage of pertussis.

Clinical efficacy of cefotaxime in serious infections.

Thirty-five patients underwent 38 treatment courses with cefotaxime. Documented infections included 11 bacteremias, 7 cases of nosocomial pneumonia, 6 surgical wound infections, 3 bone infections, 1 biliary infection, and 1 urinary tract infection. Granulocytopenic patients with fever received 15 courses of empiric cefotaxime therapy alone; in 8 courses, no definite site of infection or pathogen was isolated. Broad-spectrum antibiotics had been administered to 23 patients before cefotaxime. Thirty-seven bacterial pathogens were isolated from 25 patients. Three such pathogens were resistant to cefotaxime and required alternative therapies. Pathogenic isolates included 13 Serratia marcescens, 12 Pseudomonas aeruginosa, 4 Escherichia coli, 2 Klebsiella pneumoniae, 2 Providencia stuartii, 1 Enterobacter cloacae, 1 Haemophilus influenzae, 1 Enterococcus, and 1 Staphylococcus aureus. Of the treatment courses, 25 of 38 resulted in a favorable response to cefotaxime, including 9 of 15 in granulocytopenic patients. Superinfection was seen in one patient. The emergence of resistance was documented in another patient. Of 15 patients with multiply resistant pathogens, 12 improved with cefotaxime. Of 12 patients with Pseudomonas aeruginosa, 6 favorably responded. Possible complications of cefotaxime were observed in 14 of 42 treatment courses. Cefotaxime is most useful in treatment of infections due to multiply resistant, gram-negative pathogens other than Pseudomonas aeruginosa.

Bacteriologic and clinical applications of a new extended-spectrum parenteral cephalosporin

Although third-generation cephalosporins have been considered the backbone of antibiotic therapy for the treatment of many kinds of serious infections, including those in hospitalized patients, lack of activity against some important pathogens still exists among currently available drugs. In addition, increasing accounts of antibiotic resistance, particularly in the hospital environment, are of deep concern and have thus led to the need for the development of newer antimicrobial agents. Cefepime is a now parenteral cephalosporin with an extended spectrum of antibacterial activity that includes both aerobic gram-negative and gram-positive bacteria. It is also active against many gram-negative organisms resistant to ceftriaxone and cefotaxime, as well as many strains of Enterobacter and Citrobacter resistant to ceftazidime. Cefepime appears to be less likely to select out resistant organisms, and it may be less likely to change hospital flora than currently available antimicrobials. Cefepime has been shown to be very well tolerated and effective in the treatment of a variety of infections including moderate-to-severe pneumonia (including cases associated with concurrent bacteremia), complicated and uncomplicated urinary tract infections (also including cases associated with concurrent bacteremia), and skin and skin-structure infections. Clinical response rates are > or = 75% for most infections and have been comparable to ceftazidime in comparative trials. In addition, pretreatment susceptibility testing indicates that >94% of organisms isolated in patients enrolled in clinical trials were susceptible to cefepime.

Future trends in aminoglycoside therapy.

The aminoglycosidic aminocyclitols have been utilized extensively for three decades. Nonetheless, the future use of this class of agents has been questioned of late. Recognized inadequacies of the aminoglycosides and the development of new antibiotics with significant activity against gram-negative bacilli are commonly cited reasons for the theorized decline of these compounds. However, resistance to newly developed antibiotics already has become evident. This insures a continuing role for the aminoglycosides in the treatment of nosocomial infections. Aminoglycosides will have continued use as empiric, potentially synergistic therapies for hospital-acquired infections in neutropenic patients with bacteremia, in enterococcal endovascular infections, and in patients with serious infections associated with Pseudomonas aeruginosa. Those factors that will influence the future role of aminoglycosides in these settings will include economic, administrative, and space pressures to restrict the number of antibiotics available in hospitals, the discovery of novel antibiotics, the utility of combination therapies employing an aminoglycoside and newly available drugs, the comparative toxicities of new antimicrobial regimens, and considerations of cost containment.