Conference Summaries: ICAAC 2000, IDSA 2000, and ASTMH 2000: Part II
Conference Summaries: ICAAC 2000, IDSA 2000, and ASTMH 2000: Part II
conference coverage
Editor’s Note: The following summaries represent a selection of papers dealing with subjects other than HIV infection from those presented at the three meetings listed below. It is important to recognize that many of these summaries are extracted only from the published abstract and it is possible that some of the material presented at the conference may have differed. The abstracts can be found on-line at the URLs given. The 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Toronto, Canada, Sept. 17-20, 2000; http://www.asmusa.org. The 38th Annual Meeting of the Infectious Diseases Society of America (IDSA), New Orleans, La, Sept. 7-10, 2000; http://www.idsociety.org. The 49th Annual Meeting of the American Society of Tropical Medicine and Hygiene (ASTMH), Houston, Tex, Oct. 29-Nov. 2, 2000; http://www.astmh.org. —Stan Deresinski, MD, FACP
Nosocomial & Nosohusial Infection
Hospital Epidemiology
What at first appeared to be a significant increase in the incidence of nosocomial infections was instead determined to be a pseudo-outbreak, likely caused by increased diagnosis by physicians. The latter occurred in response to the insititution of an antibiotic control program as a result of a need to justify antibiotic prescriptions. (IDSA #19.)
Antibiotic-resistant bacteria, including S. aureus, enterococci, and Gram-negative bacilli were recovered from a small proportion of scissors used by health care workers. Of 54 toys brought into the children for hospitalized children, all yielded bacteria on culture, including coagulase-negative staphylococci (78%), S. aureus (18%), and Pseudomonas spp. (3%). (ICAAC #2334, #1589.)
Transient streptococcal bacteremia was detected in six of 68 (8.8%) patients immediately after urgent orotracheal intubation. No bacteremia was detected before or one hour later. Thus, blood cultures obtained in this setting must be interpreted with caution. (ICAAC # 1736.)
Two distinct clusters of infection with Serratia marcescens resistant to imipenem were traced to a con-taminated reusable saline dropper bottle used for wound dressings in an outpatient office. (ICAAC #1178.) An outbreak of P. aeruginosa infection in a newly renovated reverse isolation unit resulted from exposure to hospital water. An outbreak of infection with a clonal strain of a previously undescribed ESBL-producing member of the Enterobacteriaceae, called Enteric Group 137, caused an outbreak of infection at a single hospital. (ICAAC #1175, IDSA #7.)
The continued emergence of resistant Gram-negative hospital pathogens has led to both new looks at old drugs and the development of new agents. Only one clinical and bacteriological failure was observed among 14 evaluable patients infected by Enterobacteriacea producing extended spectrum beta lactamase (ESBL) and/or AmpC cephalosporinase after treatment with cefepime. Colistimethate sodium (colistin) administration was safe and efficacious in five pediatric burn patients with infections due to mulitple-resistant P. aeruginosa. Thirty patients with infection due to multi-drug resistant P. aeruginosa were treated with colistin for a mean duration of 18.5 days without evidence of nephrotoxicity or neurotoxicity. (ICAAC #1716, #962, #1724.)
Administration of piperacillin/tazobactam in a dose of 9 g every 12 hours was well tolerated in healthy volunteers and maintained serum concentrations above the MIC for 50% or more of the dosing interval (% T > MIC) for organisms with MICs of 32 mcg/mL or less. Administration of 6.75 g every 12 hours was associated with 50% or more of T greater than MIC for organisms with MICs of 16 mcg/mL or less. (ICAAC #2249.)
MK-0826, a long, half-life 1-b-methyl injectable carbapenem, is active against multiple strains of ESBL-producing and plasmid-mediated AmpC producing Enterobacteriaceae, as well as against penicillin- and fluoroquinolone-resistant pneumococci. Like other carbapenems, it is inactivated by metallo-b-lactamases. Its activity against anaerobes is similar to that of imipenem and meropenem. (ICAAC #380, #383, #387.)
The increasing number of immunocompromised patients provides a background for hospital-acquired fungal infections. Six neutropenic patients with hematological disease developed invasive infection due to Scedosporium prolificans; all six died. Institution of "aerial control measures" was followed by an absence of further cases. (ICAAC #1177.)
Fungemia due to Exophiala jeanselmei was detected in 23 patients in less than a year at one institution. A multivariate analysis found that use of corticosteroids, the presence of neutropenia, and prolonged hospitalization were associated with infection. Environmental sampling revealed the presence of the fungus in deionized water in the pharmacy used to prepare antiseptic solutions, in one water tank, and from a sink in a nonpatient care area. The clinical isolates and those from the pharmacy water appeared genotypically identical; discontinuation of the use of this water was followed by cessation of the appearance of new cases of fungemia. (ICAAC #1174.)
An outbreak of Q fever occurred in kitchen workers at a hospital in Jerusalem. (ICAAC #1176.)
Azithromycin was superior to placebo as prophylaxis against the development of severe respiratory illness in employees, although not organism colonization, during a hospital outbreak of Mycoplasma pneumoniae pneumonia. (IDSA #178.)
A case-control study in stem cell transplant recipients with indwelling Hickman catheters found that the following were independent risk factors for bloodstream infections (BSI): self-administration rather than administration of infusions by a care giver; a lower frequency of change of needle-less IV device (ND) system; and a higher frequency of bathing. After introduction of improved patient education, increasing the frequency of ND change to twice weekly, and the use of Parafilm to protect the ND to Hickman connection during bathing, the incidence of BSI was reduced by more than one-half. (ICAAC #1424.)
The use of a chlorhexidine-impregnated sponge placed over the insertion site of short-term arterial and central venous catheters significantly reduced the risk of catheter colonization and catheter-related BSI. (ICAAC #1430.)
Urinary Tract Infection
Treatment of asymptomatic bacteriuria in women with diabetes mellitus did not affect the incidence of subsequent symptomatic cystitis, but did decrease the incidence of pyelonephritis. Maintenance of sterile urine did not affect renal function. (ICAAC #1750.)
A total of 22.9% of 2189 urine isolates of E. coli from women with community-acquired urinary tract infection in Mallorca were resistant to ciprofoxacin. (ICAAC #1753.)
Skin & Soft Tissue Infection
One hundred eighteen cases of olecranon septic bursitis were seen in Calgary over 21 months. Fewer than 20% were febrile, defined as a temperature higher than 37.8°C. S. aureus was recovered from 88%. (ICAAC #1758.)
Mediastinitis
A retrospective review of 110 cases of mediastinitis after cardiac surgery found that 48% were due to coagulase-negative staphylococci (CNS), 22% to S. aureus, and 18% to Gram-negative bacilli. CNS infection was more likely to be associated with an absence of clinical signs of mediastinitis and with negative blood cultures than was infection with other organisms. (ICAAC #710.)
Viral Infections
Respiratory Viruses
Influenza & Parainfluenza Viruses. Rhabdomyolysis has been reported as a rare complication of influenza virus infection. It appears, however, that muscle breakdown is quite common in this setting. An elevated serum CPK (> 200 U/L) was found in 14 of 21 (67%) patients with influenza virus infection (16 with influenza A and 5 with influenza B). The mean CPK was 2128 U/L (range, 220-9655 U/l); no patient developed renal failure. (ICAAC #981.)
Zanamivir and oseltamivir, two neuraminadase inhibitors, were approved for use in the United States in the treatment of influenza A and influenza B virus infections in 1999. One potential value of early treatment of these infections is the prevention of complications. One common complication of influenza in children is acute otitis media. With the use of selective agar, S. pneumoniae, H. influenzae, and/or M. catarrhalis was detected in nasopharyngeal secretions in 69% of healthy children and in 79% of children during viral respiratory illness in concentrations of 103 CFU/mL or more of secretion. (ICAAC #1974.)
Oseltamivir administration is associated with rapid distribution of the drug into fluid obtained from the middle ear and paranasal sinuses in concentrations well in excess of the influenza virus IC90. (ICAAC #509.) In a randomized, placebo-controlled trial, treatment of children with influenza with oseltamivir reduced the risk of subsequent otitis media by 56% in those ages 1-5 years and by 40% in those 1-12 years of age. (ICAAC #977.)
In addition to the efficacy of these newer drugs in the treatment of influenza, recent studies indicate that, as expected, they are also as effective as prophylaxis. Residents of long-term care facilities, 86% of whom received influenza vaccination, were randomized during each of three winter seasons to receive either zanamivir (10 mg qd) or standard of care for 14 days beginning at the outset of detection of an influenza outbreak. The standard of care in this study consisted of administration of rimantidine if the outbreak was due to influenza A and placebo for influenza B. Zanamivir was superior to standard of care, including the use of rimantidine (95% of outbreaks were due to influenza A virus). (ICAAC #1155.)
Concern has been raised about the ability of debilitated elderly to correctly use the zanamivir inhaler. However, of 235 elderly residents of a long-term care facility, 196 (84%) were able to comply with inhalations of zanamivir. (IDSA #609.)
One problem with the use of amantadine and rimantadine is the emergence of resistant virus. In a clinical trial comparing zanamivir to rimantadine in the prevention of influenza outbreaks in nursing homes, no zanamivir- resistance was detected among 93 isolates over three seasons. In contrast, rimantadine-resistance was found among 38% of isolates over two seasons. Eighteen subjects developed influenza while receiving rimantadine, 10 were culture positive, and eight of these 10 were shedding resistant virus. Six developed influenza while receiving zanamivir; all six viral isolates remained susceptible to zanamivir. (ICAAC #181.)
Elderly residents of long-term care facilities, 80% of whom had received influenza vaccination, were randomized to receive either oseltamivir or placebo once daily for six weeks during a period when influenza virus infections were occurring locally. Oseltamivir administration was associated with 92% protective efficacy and reduced complications by 78%. (ICAAC #979.)
In a placebo-controlled trial that demonstrated efficacy of prophylaxis with oseltamivir, the incidence of infection in placebo-recipient contacts of a symptomatic influenza-infected family member was 20% (40/200) and more than 70% of these secondary cases were symptomatic. (ICAAC #980.)
In a randomized, placebo-controlled trial involving 1063 patients with influenza (81% influenza A), the administration of oseltamivir was associated with a mean decrease in duration of illness of 20.2% (24.2 hours). (IDSA #611.)
Thirty cases of culture-proven influenza virus infection were identified in adult solid organ transplant recipients (19 received lung) at one center over the last decade. Infection occurred a median of 2.3 years after transplantation and occurred in some despite vaccination. Twenty-one (70%) were hospitalized, five (17%) required mechanical ventilation, and eight (24%) secondarily developed bacterial pneumonia. Other complications included myocarditis and encephalitis. Tissue examination of the transplanted organ demonstrated some degree of allograft rejection in 13 of 21 (60%). (IDSA #583.)
The effective use of anti-influenza drugs in most circumstances requires the availability of rapid and accurate diagnoses. In a direct comparison, with influenza culture and DFA results as the standards, three rapid diagnostic tests—FluQIA, Quickvue Influenza Test, and Directigen Flu—were essentially equivalent, with sensitivities of 82-88% and specificities of 93-96%. A fourth test, Z Stat Flu, had comparable sensitivity but its specificity was only 73%. (IDSA #604.)
Twenty-four cases of human parainfluenza virus infection (63% HPIV-3) were identified in adult lung transplant recipients at one center over the last decade. They occurred a median of 1.4 years after transplantation. All 24 required hospitalization, seven had infiltrates on chest x-ray, and five required mechanical ventilation. Some evidence of acute allograft rejection was seen on examination of specimens obtained by transbronchial biopsy in 18 of 22 (82%). Nine patients had new onset or exacerbation of bronchiolitis obliterans. Two (8%) patients died. (IDSA #582.)
Respiratory Syncytial Virus (RSV). It is increasingly recognized that RSV is a pathogen of adults, as well as children. A total of 658 community-dwelling adults were followed through one winter season and monitored for culture evidence of RSV and influenza virus infection during episodes of respiratory illness. A total of 36% of young and more than 90% of the elderly had received influenza vaccination. RSV was detected in 22 (6.9%) of 318 evaluable illnesses while influenza virus was found in 10 (3.1%). Twelve (54.5%) of the 22 RSV infections were in the elderly. (ICAAC #184.)
An RSV subunit vaccine, BBG2Na, was safe and immunogenic in elderly patients in a Phase II trial. (ICAAC #740.)
Nine of 249 (9%) patients who underwent autologous hematopoietic stem cell transplantation at the MD Anderson Cancer Center developed RSV infection during a community-wide outbreak. Two-thirds developed pneumonia and two of these died. Treatment with aerosolized ribavirin plus IVIG may have been associated with improved outcome. (IDSA #612.)
Also at MD Anderson, 58 adults with leukemia were hospitalized with RSV infection over an eight-year period. Pneumonia developed in 40 (69%) and 41% of patients died as a consequence of pulmonary involvement. Pneumonia occurred in 84% of those who were myelosuppressed and in only 35% of those who were not. Treatment with aerosolized ribavirin plus IVIG appeared to have been associated with improved outcome in patients who had evidence of myelosuppression. (IDSA #613.)
Picornavirus. More than 50% of common colds are caused by picornaviruses, especially rhinovirus. In a placebo-controlled trial in the treatment of upper respiratory tract infection in adults, pleconaril administration was associated with a mean 1.7 day reduction in duration of rhinorrhea (P = 0.07). The decrease in duration was 2.25 days in those not taking concomitant cold medicine (P = 0.033). (ICAAC #1161.)
Adenovirus. An adenovirus 4 outbreak affected a large number of military basic trainees at a Texas base. Trainees were previously routinely vaccinated against adenoviruses 4 and 7, which is no longer available. (IDSA #81.)
Because almost 50% of pediatric hematopoietic stem cell transplant recipients at Children’s Hospital in Los Angeles developed evidence of adenovirus infection, a prospective study was initiated. Two patients had evidence of adenovirus infection at the time of transplantation, and four others developed infection at intervals ranging from 13 days to 18 months later. All six were treated with cidofovir and five became culture-negative after the first dose, although cultures again became positive despite continued drug administration in two, both of whom nonetheless remained asymptomatic. (IDSA #614.)
Herpes Viruses
Cytomegalovirus (CMV). A randomized trial performed in allogeneic bone marrow transplant recipients found that a strategy of preemptive therapy based on weekly CMV antigen testing was significantly superior to one based upon day 35 CMV screening by bronchoalveolar lavage. (ICAAC #1945.)
In a cohort of allogeneic blood or bone marrow transplant recipients, monitoring by CMV pp65 antigen testing and by COBAS Amplicor Monitor CMV test were of comparable efficacy. (ICAAC #1946.)
Preemptive oral administration of ganciclovir to patients with CMV pp65 antigenemia was effective, relative to placebo, in prevention of CMV disease in liver transplant recipients, and was also cost effective. (ICAAC #1944.)
Orally administered ganciclovir given preemptively to liver transplant recipients with CMV DNA detected in blood by PCR was effective, relative to placebo, in the prevention of CMV infection. However, weekly PCR was relatively ineffective in predicting early CMV infections, particularly in donor positive, recipient negative subjects because many developed infection coincident with the first positive PCR. (ICAAC #1943.)
CMV presented in an atypical fashion in five patients 6 months to 22 years (median, 25 months) after solid organ transplantation. Four had been at risk of primary CMV infection. Three were afebrile, WBC was elevated in four, and platelet count was normal in four. Two had CMV pneumonia (without hypoxia), two had enterocolitis, and one had chronic colitis. (ICAAC #1592.)
A randomized trial of 100 neonates with symptomatic congenital CMV infection involving the CNS found that six weeks of therapy with ganciclovir protected against hearing deterioration, but was significantly associated with the development of neutropenia in the majority. (ICAAC #1942.)
Herpes Simplex Virus (HSV). Valacyclovir, 500 mg daily, was more effective than placebo in the prophylaxis of both herpes labialis and herpes galdiatorum. The latter is a recurrent HSV-1 infection primarily seen on the torso, neck, face, and scalp and is believed to afflict 75,000 wrestlers in the United States. (ICAAC #464, #465.)
Valacyclovir and acyclovir were equally effective and tolerable in the prevention of mucocutaneous HSV infection in neutropenic patients. (IDSA #616.)
Varicella-Zoster Virus (VZV). A total of 177 adults, adolescents, and children with chickenpox were randomized in a placebo-controlled blinded trial to receive acyclovir beginning within 24, 48, or 72 hours of the onset of skin lesions. The earlier treatment was initiated, the more effective the therapy—there was evidence of benefit when intiated within 48 hours in children and adolescents, but not in adults. Shedding of VZV ceased a median of 2.5 days after initiation of therapy; emergence of resistance was not detected. (ICAAC #469.)
Placebo or acyclovir (10 mg/kg IV q8h for 14 days followed by 800 mg po q6h for 42 days) was administered to 10 patients who had had post-herpetic neuralgia for longer than six months. No benefit to antiviral therapy could be detected. (ICAAC #772.)
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