Periumbilical parasitic thumbprint purpura: strongyloides hyperinfection syndrome acquired from a cadaveric renal transplant.

Periumbilical parasitic thumbprint purpura may be a presenting sign of hyperinfection strongyloidiasis in the immunocompromised host. We report a case of fatal hyperinfection strongyloidiasis acquired from a cadaveric renal allograft, diagnosed by the pathognomonic periumbilical thumbprint purpuric eruption, confirmed by skin biopsy and laboratory testing.

Infections during left ventricular assist device support do not affect posttransplant outcomes.

BACKGROUND: Although infections acquired during ventricular assist device support may increase the risk of infection and have an impact on transplant survival, their true posttransplant consequences remain to be determined. This study evaluates the impact of an outpatient program, newer devices, and an updated infection management protocol on infection-related patient outcomes after transplant. METHODS AND RESULTS: Eighty-six patients received a left ventricular assist device (LVAD) between June 1996 and June 1999. Fifty patients transplanted during the same period, without prior device support, were used as controls; they were matched to transplanted LVAD recipients by age, sex, diagnosis, and transplant date. The nature of and actuarial freedom from peritransplant and posttransplant infections were compared at 6 months after transplant; actuarial patient survival was compared at 3 years. Infection was defined as leukocytosis or leukopenia, with a positive culture requiring either medical or surgical intervention. Forty-four patients (51%) were successfully discharged home on LVAD support, and 61 (71%) were transplanted. A high incidence of infection during device support did not have an impact on pretransplant or posttransplant mortality, posttransplant infectious rate, or overall patient survival. Active infections at transplant also did not significantly influence 6-month mortality. In comparison, LVAD recipients had a lower freedom from infection than did controls (P:<0.05); however, 3-year survival did not differ: 79% and 87% for the LVAD and control groups, respectively. CONCLUSIONS: Although LVADs increase the risk of infection in the early posttransplant period, this appears not to have an impact on transplantability or patient survival and likely reflects effective infection control in both inpatient and outpatient settings.

The influence of infection on survival and successful transplantation in patients with left ventricular assist devices.

BACKGROUND: Mechanical cardiac assistance has recently emerged as a tenable option in the treatment of end-stage heart failure. In spite of recent technical improvements that have reduced the incidence of life-threatening complications, the reported frequency of infections in these patients has remained high. METHODS: Over a 5-year period, 60 patients underwent insertion of a left ventricular assist device (LVAD) at our institution. Detailed medical records were kept prospectively for all patients, and a variety of endpoints were analyzed, including the incidence, nature, and sequelae of infections before and after LVAD implantation and after transplantation. RESULTS: Twenty-nine of 60 patients (48%) undergoing LVAD insertion subsequently had development of infections. The most frequent sites of infection were blood, LVAD drivelines, and central venous catheters, representing 61% of all infections. At the time of LVAD implantation, 13 of 60 patients (22%) had culture-proven infections. In spite of an increased incidence of subsequent infection (77% vs 40%), there were no differences in rates of mortality (31% vs 26%), LVAD endocarditis, (23% vs 11%) and eventual transplantation (62% vs 57%) between these patients and those without periimplantation infections. Although the overall mortality rate was not influenced by infections during LVAD support (28% vs 26%), the development of LVAD endocarditis was associated with a high mortality rate. Finally, although patients with infections during LVAD support had significantly longer median support times than those who remained infection free (101 vs 49 days, respectively), there was no difference in the rate of successful transplantation (59% vs 58%) or in the rate of infection after transplantation (35% vs 28%). CONCLUSIONS: Infections are common in patients undergoing LVAD support, but they do not adversely affect survival, the rate of successful transplantation, or the incidence of posttransplantation infection. Periimplantation infections may increase the risk of subsequent infections, but they also do not influence survival or transplantability. Patients with development of LVAD endocarditis are at increased risk for morbidity and death and require early and aggressive therapy, potentially including device explantation.

Elimination of Staphylococcus aureus nasal carriage in health care workers: analysis of six clinical trials with calcium mupirocin ointment. The Mupirocin Collaborative Study Group.

Six double-blind, independently randomized studies evaluated the efficacy and safety of calcium mupirocin ointment in eliminating nasal carriage of Staphylococcus aureus among health care workers. Healthy volunteers with stable nasal carriage of S. aureus (n = 339) received either calcium mupirocin ointment (n = 170) or an identical placebo ointment (n = 169) intranasally for 5 days. Nasal carriage was eliminated 48-96 hours after completion of treatment in 130 (91%) of 143 evaluable volunteers receiving mupirocin but in only 8 (6%) of 142 evaluable volunteers receiving placebo. The 85% crude difference represents a 90% pooled (adjusted) estimate of the risk difference (95% confidence interval, 0.86-0.95) and a risk ratio of 16 (P < .0001). This effect of treatment with mupirocin was observed consistently (risk ratio, 8-32) in all six centers. In addition, 96 of the 130 mupirocin-treated volunteers and 1 of the 8 placebo-treated volunteers who were culture-negative at the end of therapy remained free of S. aureus 4 weeks after treatment. Adverse events in each treatment arm were mild and equally frequent. These data, consistent across six institutions, demonstrate that calcium mupirocin ointment administered intranasally for 5 days is safe and effective in eliminating stable nasal carriage of S. aureus.

Mupirocin treatment of nasal staphylococcal colonization.

The effectiveness and safety of mupirocin calcium ointment applied to the anterior part of the nares for 5 days in the eradication of nasal carriage of Staphylococcus aureus was investigated in a placebo-controlled, double-blind study. Subjects were healthy medical center staff who had two positive cultures of the anterior nares for S aureus. Antimicrobial susceptibility, phage typing, and restriction endonuclease analysis of plasmid DNA were used to monitor the identity of relapsing and persisting strains. Mupirocin eliminated 74% of S aureus at early follow-up and 91% of original strains. At 4 weeks, 78% of the original strains were eradicated, whereas all of the placebo group remained colonized. Recolonization with mupirocin-resistant strains occurred in six patients, but these were of different phage and plasmid types from the original isolates. None of the subjects had serious adverse effects. Applied intranasally for 5 days, a calcium preparation of mupirocin in a paraffin base is effective in eliminating S aureus nasal carriage and is well tolerated.

Home intravenous antibiotic therapy.

Intravenous therapy for a variety of infections can be performed in the home setting; the therapy is safe and relatively cost effective. Close monitoring of the patient to ensure good care is essential. In the coming years, the variety of infections treatable at home will increase.

Bactericidal activity of clarithromycin and its 14-hydroxy metabolite against Haemophilus influenzae and streptococcal pathogens.

The serum bactericidal activity of clarithromycin in six normal human volunteers was determined after oral doses of 500 mg. The mean plasma levels of clarithromycin plus 14-hydroxy clarithromycin were 2.11 micrograms/mL after the second dose and 4.36 micrograms/mL after the sixth dose. The mean serum bactericidal titer against Haemophilus influenzae after the second dose was 1:8 and after the sixth dose 1:16 when unheated serum was used. Similar values were obtained when serum to which clarithromycin and 14-hydroxy clarithromycin was added was tested. Mean serum bactericidal titers against H. influenzae determined in Haemophilus test broth or heated serum were 1:2 and 1:4, respectively. Against Streptococcus pneumoniae and Streptococcus pyogenes, there was greater than 1:16 serum bactericidal levels at 12 hours after the sixth dose of clarithromycin.

Oral ofloxacin therapy of infections due to multiply-resistant bacteria.

We determined the efficacy and safety of orally administered ofloxacin, 400 mg twice daily, in the treatment of infections due to multiply-resistant bacteria. Patients (n = 99) were treated for 84 infections in 82 patients evaluable for efficacy with a bacteriologic response of 71%. Organisms treated included Pseudomonas aeruginosa (39), Staphylococcus aureus (11), Serratia marcescens (9), Enterobacter species (7), five each of Escherichia coli, Citrobacter, Salmonella, Klebsiella, and other organisms. The overall clinical responses was 89%: 28 (90%) of 16 osteomyelitis, 10 (83%) of 12 urinary tract infections, and three of three bacteremias. Insomnia occurred in 27% and responded to dose reduction. Resistance of P. aeruginosa to ofloxacin developed in 15% of isolates. No hepatic, renal, or hematologic toxicity developed in spite of long therapy, 283 days. Ofloxacin was an effective therapy for lower respiratory, urinary, bone, and soft tissue infections due to multiply-resistant Gram-negative bacteria and is effective for selected Staphylococcus aureus infections.

The use of cefepime (BMY 28142) to treat respiratory infections.

Cefepime, an aminothiazolyl cephalosporin active against Gram-positive and Gram-negative bacteria, was used at a dose of 1 g every 12 hours to treat respiratory and other infections in 29 patients. All 19 patients from whom an organism was cultured responded clinically and microbiologically. The patients had underlying risk factors of human immune virus positive status, 58%, and chronic lung disease, 19%. Cefepime was well tolerated. Organisms eradicated included Streptococcus pneumoniae and Haemophilus influenzae. Further study will define cefepime's role in hospital-acquired respiratory infection.

Metronidazole.

Metronidazole is a highly effective therapy for anaerobic infections and a variety of protozoal and parasitic diseases. Its pharmacokinetics, toxicities, and unique mode of action are reviewed in detail. Indications for use and respective dosages are suggested.

Determination of acquired immunodeficiency syndrome (AIDS) after renal transplantation.

Diagnosing the acquired immunodeficiency syndrome (AIDS) in transplant recipients can be difficult due to the patient's medication-induced immunosuppressed state. We report two renal allograft recipients who acquired HIV infection at the time of transplantation and later went on to develop multiple opportunistic infections. Careful documentation of HIV antibody status of the donor and recipient, when available, the nature of immunosuppressive therapy used, the type of infections and their timing after transplantation, as well as the patient's absolute T4 lymphocyte count, T cell ratio, and B cell humoral response to infection were used as factors to distinguish between infection related to immunosuppressive therapy and that seen in HIV-induced immunodeficiency. Reduction in immunosuppressive therapy because of the HIV-related immunodeficiency state did not result in allograft rejection. Both patients died of their multiple infections. The determination of AIDS in the transplant recipient has both therapeutic and prognostic significance. This diagnosis should be considered when transplant patients develop unusual infections in relationship to their posttransplant course.

Streptococcus agalactiae (group B) endocarditis--a description of twelve cases and review of the literature.

The 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.

Ciprofloxacin therapy in cystic fibrosis.

There is great need for an oral agent that could be used to treat pulmonary exacerbations in patients with cystic fibrosis. In this study, the use of oral ciprofloxacin as sole therapy was evaluated in 18 patients with 39 infectious episodes; 13 episodes were classified as severe, 19 were classified as moderate, and seven were classified as mild. Patients ranged in age from eight to 36 years (mean, 23 years). Dosage varied according to severity of disease, body size, and the susceptibility of the Pseudomonas isolate to ciprofloxacin; the dose ranged from 750 to 2,250 mg daily (mean, 1,800 mg). Ten patients received one course of ciprofloxacin, and eight received repeated courses. The overall clinical response rate was 82 percent. There was a response to the initial treatment course in 96 percent of the patients. Those in whom therapy failed had been re-treated with ciprofloxacin and were severely ill. Failure to respond correlated poorly with pretreatment minimal inhibitory concentration (MIC) values (0.6 microgram/ml for failures versus 0.4 microgram/ml for responses). Pseudomonas could not be eradicated from the sputum of any of the patients, although there was a marked reduction in purulence and bacterial counts. In general, patients who did not require re-treatment for three months would again have susceptible organisms. When organisms became resistant to ciprofloxacin (MIC greater than 2 micrograms/ml), they showed no concomitant new aminoglycoside or beta-lactam resistance. No serious toxicity occurred in any of the 39 episodes of treatment. In seven patients treated with combination therapy (tobramycin or azlocillin), the infecting organisms were reduced in number, but eradication of Pseudomonas generally could not be achieved. Increases in MIC occurred during combination therapy. Ciprofloxacin is a major advance in the treatment of bronchopulmonary infection in patients with cystic fibrosis.

Treatment of serious infections with intravenous ciprofloxacin.

Thirty-four patients were treated with intravenous ciprofloxacin. Thirty infections occurring in 28 patients were assessable for the efficacy analysis. The drug dosage was 300 mg every 12 hours in 19 patients and 200 mg intravenously every 12 hours in nine patients. Twelve patients were also given ciprofloxacin orally after initial intravenous therapy. The mean duration of total therapy was 31 days. The overall clinical response rate was 87 percent, and the bacteriologic response rate was 70 percent. Favorable responses were observed in 10 of 12 patients with osteomyelitis/septic arthritis; seven of eight with soft tissue infection; four of four with pneumonitis; one of two with cystic fibrosis; and four of four with urinary tract infections. Resistance to ciprofloxacin developed in three Pseudomonas aeruginosa isolates. Toxicity was minor: phlebitis occurred in six patients, nausea in six, and rash in one. Intravenously administered ciprofloxacin or intravenous ciprofloxacin followed by oral ciprofloxacin is a safe and effective therapy for serious infections.

Effect of ciprofloxacin on fecal flora of patients with cystic fibrosis and other patients treated with oral ciprofloxacin.

Ciprofloxacin is a fluorinated carboxyquinolone that inhibits Enterobacteriaceae, staphylococci, and Pseudomonas at low concentrations. It has poor activity against Bacteroides fragilis. In this study, the effect of administration of ciprofloxacin on bowel flora was determined in patients treated for different infections. Patients, aged 22 to 70 years, were treated with 500 mg of ciprofloxacin every 12 hours or 750 mg every eight hours for seven to 42 days. Some patients had advanced cystic fibrosis; other patients had infections with resistant bacteria. Infecting organisms were Pseudomonas aeruginosa, Staphylococcus aureus, Serratia, and Acinetobacter. Sites of infections were lung, soft tissue, and urinary tract. Stool samples were evaluated initially, during therapy, and after therapy. No resistant gram-negative aerobic species emerged; five patients had yeast colonization, staphylococci were found in three patients, and streptococci were found in one patient. Ciprofloxacin did not select resistant gram-negative bacteria in the stool, although sputum isolates showed increases in minimal inhibitory concentrations. Resistant bacteria were not selected in the fecal flora of patients who had received beta-lactam and aminoglycoside antibiotics before therapy with ciprofloxacin.

Oral ciprofloxacin therapy of infection caused by multiply resistant bacteria other than Pseudomonas aeruginosa.

Of 125 patients treated with ciprofloxacin at the Columbia-Presbyterian Medical Center, New York, 34 had infections due to bacteria other than Pseudomonas aeruginosa. The mean age of the patients was 50 years (19-88 years) and most had significant underlying disease. There were nine lower respiratory infections, eight urinary tract infections, eight soft tissue infections, three osteomyelitis, and three intra-abdominal infections. The pathogens were: Escherichia coli, 7 (mean MIC 0.07 mg/l); Serratia marcescens, 6 (0.2 mg/l); Enterobacter spp., 5 (0.1 mg/l); Klebsiella pneumoniae, 3 (0.1 mg/l); Proteus mirabilis, 3 (0.06 mg/l); Cutrobacter freundii, 2 (0.06 mg/l), Staphylococcus aureus, 3 (0.5 mg/l); and one each of Acinetobacter anitratus. Haemophilus, influenzae, Salmonella enteritidis, Flavobacterium meningosepticum, and Streptococcus faecalis. Of these organisms 81% were resistant to ampicillin, 70% to carbenicillin, 22% to gentamicin, 49% to cefazolin and cephalexin, and 25% to cotrimoxazole. Ten patients had concomitant Ps. aeruginosa infections. Patients were treated orally with 500 mg or 750 mg ciprofloxacin every 12 h. The overall clinical response rate was 88%, and the bacteriological response 76%, and 65% if Ps. aeruginosa is included. Resistance to ciprofloxacin developed in one Staph. aureus and one Ser. marcescens (MIC greater than 2 mg/l). Toxicity was minor. Ciprofloxacin was effective and safe therapy of infections due to Gram-negative bacteria resistant to many of the currently available oral and parenteral agents.

Oral ciprofloxacin therapy of infections due to Pseudomonas aeruginosa.

The efficacy and safety of oral ciprofloxacin, a fluoroquinolone, were evaluated in the treatment of infection due to Pseudomonas aeruginosa. 96 infections in 71 patients were treated. Substantial underlying disease was present in most of the patients, and 25 (35%) were seriously ill. 52% of pseudomonas isolates were carbenicillin-resistant, and 31% gentamicin-resistant. The overall clinical response rate was 77%-28 of 35 exacerbations of cystic fibrosis respiratory disease, 17 of 19 urinary infections, 4 of 6 osteomyelitis, and 11 of 15 soft tissue infections. The bacteriological cure rate was 34%-0 of 35 cystic fibrosis, 4 of 17 respiratory infections, 17 of 19 urinary infections, 4 of 6 osteomyelitis, and 8 of 15 soft tissue infections. Ps aeruginosa developed resistance to ciprofloxacin in 25 of 96 infections. Side-effects were generally slight with nausea in 14 (15%) the most common, and there were only two substantial superinfections.

Treatment of lower respiratory tract infections due to Pseudomonas aeruginosa in patients with cystic fibrosis.

Twelve patients who underwent 26 episodes of lower respiratory tract infection due to Pseudomonas aeruginosa were treated with aztreonam. Infectious episodes were severe in 11 patients, moderate in 10 patients, and mild in five patients. In 85% of the episodes, significant clinical improvement occurred, but in four severe episodes, the clinical response was unsatisfactory. The mean interval between initiation of treatment and improvement was seven days. Aztreonam was as clinically effective in the treatment of infections due to organisms susceptible to penicillins active against Pseudomonas as it was in the treatment of infections due to organisms resistant to these agents. P. aeruginosa was not permanently eradicated from the sputum of any of the patients treated with aztreonam. It did not cause any major adverse effects, and the only laboratory abnormality found was an increase in alkaline phosphatase, which occurred during 12 (46%) courses of therapy. Levels of alkaline phosphatase returned to normal after conclusion of treatment. Aztreonam was shown to be clinically effective in the treatment of lower respiratory infections due to P. aeruginosa in patients with cystic fibrosis.

Clinical experience with aztreonam in the treatment of gram-negative bacteremia.

Aztreonam was used for the treatment of gram-negative bacteremia in 101 patients. In 34 instances a second antibiotic was prescribed for the treatment of suspected or documented gram-positive or anaerobic infection. The sources of bacteremia were the urinary tract (50 patients), an intraabdominal site (17), the respiratory tract (8), an intravascular site (9), and an unknown site (17). The clinical response rate was 92% (91 of 99 patients). The bacteriologic response rate was 97% (98 of 101 patients). In six of seven patients, Pseudomonas aeruginosa bacteremia was cured. Twelve patients developed superinfection with gram-positive cocci or Candida, and one patient developed diarrhea associated with Clostridium difficile. No other serious toxic effects were noted.