ICAAC/IDSA/ASTMH 2003

Conference Coverage

The following is a summary of selected abstracts from 3 meetings. The 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) met in Chicago September 14-17, 2003. The Infectious Disease Society of America (IDSA) met in San Diego October 9-12, 2003. The American Society of Tropical Medicine and Hygiene met in Philadelphia December 3-7, 2003. — Stan Deresinski, MD, FACP

Skin and Soft-Tissue Infections

Independent risk factors for recurrent lower-extremity cellulitis were the presence of tinea pedis, increased body mass index, current tobacco use, and history of deep-venous thrombosis (IDSA 279).

B fragilis and peptostreptococcal isolates from diabetic foot ulcers were significantly more resistant to levofloxacin, moxifloxacin, gatifloxacin, and gemifloxacin than were isolates from intra-abdominal infections (IDSA 484).

Patients with uncomplicated cellulitis were treated with levofloxacin 500 mg q.d. After 5 days they were randomized to either complete a total duration of therapy of 10 days or to discontinue therapy, with resultant clinical cures of 97% and 98%, respectively. Combined analysis of 2 phase III studies of patients with skin and skin-structure infections in which patients received either daptomycin, vancomycin, or a semisynthetic penicillin found overall equivalent clinical success rates (IDSA 312, ICAAC L-737).

Two randomized trials concluded that linezolid was superior to vancomycin in skin and soft-tissue infections due to MRSA:

  • Orally administered linezolid was superior to IV vancomycin in a randomized, open-label trial involving patients with lower-extremity cellulitis due to MRSA and requiring surgical intervention (IDSA 313).
  • Linezolid was as effective as comparators (vancomycin or antistaphylococcal penicillin) in the treatment of patients with complicated skin and soft-tissue infections in a randomized trial. Linezolid was superior to vancomycin in MRSA-infected patients who were microbiologically evaluable, with success rates of 94% and 84%, respectively (P = .0108) (IDSA 314).

Two randomized trials compared ertapenem and piperacillin/tazobactam:

  • In a randomized trial of a total of 118 patients with serious complicated cellulitis, response rates in evaluable patients were achieved in 90% of ertapenem (1 g q24h) and 84% of piperacillin/tazobactam (3.375 g q6h) recipients (IDSA 316).
  • In a randomized trial of treatment of lower-extremity infections in diabetics, clinical cure was achieved at the end of therapy in 82% of recipients of ertapenem 1 g q24h and 76% of recipients of piperacillin/ tazobactam 3.375 g q6h (IDSA 321).

Infections in Transplant Recipients

A meta-analysis of 4 randomized clinical trials failed to identify a beneficial effect of selective digestive tract decontamination in liver transplant recipients. Another meta-analysis concluded that fluconazole prophylaxis significantly reduces the incidence of early invasive fungal infections in liver transplant recipients but does not reduce mortality. In contrast, however, a randomized trial found that, despite receipt of attempted prophylaxis with either fluconazole (400 mg q.d.) or liposomal amphotericin B (2 mg/kg/d), 14% of 68 high-risk liver transplant recipients developed invasive fungal infection with no apparent difference between the 2 treatment groups (ICAAC K-1373, M-968, IDSA 133).

Invasive aspergillosis remains a common and potentially fatal complication in patients who have received reduced-intensity allogeneic stem cell transplants, occurring in 7.6% of 185 patients. Invasive peritonitis due to Aspergillus spp. is associated with high mortality in liver transplant recipients (IDSA 388, 390).

A retrospective nested case-control study of 56 liver transplant recipients with 101 infected intrahepatic and perihepatic bile collections (bilomas) found that important predictors of this complication included hepatic artery thrombosis and a Roux biliary anastomosis, while administration of ursodeoxycholic acid was protective. The pathogens most commonly isolated from the bilomas were coagulase-negative staphylococci (29%), Enterococcus spp. (26%), and Candida spp. (16%) (ICAAC K1377).

A study of the molecular epidemiology of invasive Candida infection in the first 100 days after orthoptic liver transplantation found that unique yeast stably colonize these patients and that early infections are commonly of intra-abdominal, particularly gastrointestinal tract, origin (ICAAC M-2062).

Sixty-two percent of Viridans group streptococci isolated during prophylactic administration of gatifloxacin and penicillin to bone marrow transplant recipients had a resistant rate to gatifloxacin of 62%. In a shift in etiologic pathogens, Gram-negative bacteria have emerged as predominant pathogens in bacteremic liver transplant recipients at the Pittsburgh VAMC. Another group reported that prophylaxis against herpesvirus infections with ganciclovir was independently associated with a significant reduction in the incidence of bacteremia in orthoptic liver transplant recipients (IDSA 214, ICAAC K-1371, ICAAC V-1287).

A retrospective study found that valganciclovir was as effective as oral ganciclovir when administered preemptively for the prevention of CMV disease in liver transplant recipients. In addition, a 94% clinical and virological response rate in transplant patients with CMV infection was achieved with administration of valganciclovir. In the patients with viremia, the mean time from onset of therapy to antigen negativity was 9.7 days (range, 4-22 days) (ICAAC V-285, IDSA 366).

Two cases of fatal fulminant hepatic failure in allogeneic bone marrow recipients due to adenovirus are described. A retrospective analysis of allogeneic HSCT recipients with disseminated adenovirus infection found that 75% of those treated with cidofovir died, while 83% of those untreated did so, a difference that was not significant. Cidofovir administration was associated with nephrotoxicity in 83% of recipients. The in vitro susceptibility of adenovirus to ribavirin was highly dependent on viral genogroup, with isolates of genogroups A, B, D, and E all being resistant and those of genogroup C being inhibited by the drug (IDSA 370, ICAAC K-1375, V-282).

BK viruria was present in 13% of nonrenal solid organ transplant recipients with unexplained chronic renal disease (IDSA 372).

Hypogammaglobulinemia occurred in 61% of nonmyeloablative allogeneic peripheral stem cell transplant recipients at a mean time of 2.5 months for the first low IgG level and 5.4 months for its nadir. It was strongly associated with the development of complete chimerism by 4 months post-transplantation (IDSA 400).

Antibiotic Management & Hospital Epidemiology

A meta-analysis of 4 randomized clinical trials failed to identify a beneficial effect of selective digestive tract decontamination in liver transplant recipients. Another meta-analysis concluded that fluconazole prophylaxis significantly reduces the incidence of early invasive fungal infections in liver transplant recipients but does not reduce mortality. In contrast, however, a randomized trial found that, despite receipt of attempted prophylaxis with either fluconazole (400 mg q.d.) or liposomal amphotericin B (2 mg/kg/d), 14% of 68 high-risk liver transplant recipients developed invasive fungal infection with no apparent difference between the 2 treatment groups (ICAAC K-1373, M-968, IDSA 133).

Invasive aspergillosis remains a common and potentially fatal complication in patients who have received reduced-intensity allogeneic stem cell transplants, occurring in 7.6% of 185 patients. Invasive peritonitis due to Aspergillus spp. is associated with high mortality in liver transplant recipients (IDSA 388, 390).

A retrospective nested case-control study of 56 liver transplant recipients with 101 infected intrahepatic and perihepatic bile collections (bilomas) found that important predictors of this complication included hepatic artery thrombosis and a Roux biliary anastomosis, while administration of ursodeoxycholic acid was protective. The pathogens most commonly isolated from the bilomas were coagulase-negative staphylococci (29%), Enterococcus spp. (26%), and Candida spp. (16%) (ICAAC K1377).

A study of the molecular epidemiology of invasive Candida infection in the first 100 days after orthoptic liver transplantation found that unique yeast stably colonize these patients and that early infections are commonly of intra-abdominal, particularly gastrointestinal tract, origin (ICAAC M-2062).

Sixty-two percent of Viridans group streptococci isolated during prophylactic administration of gatifloxacin and penicillin to bone marrow transplant recipients had a resistant rate to gatifloxacin of 62%. In a shift in etiologic pathogens, Gram-negative bacteria have emerged as predominant pathogens in bacteremic liver transplant recipients at the Pittsburgh VAMC. Another group reported that prophylaxis against herpesvirus infections with ganciclovir was independently associated with a significant reduction in the incidence of bacteremia in orthoptic liver transplant recipients (IDSA 214, ICAAC K-1371, ICAAC V-1287).

A retrospective study found that valganciclovir was as effective as oral ganciclovir when administered preemptively for the prevention of CMV disease in liver transplant recipients. In addition, a 94% clinical and virological response rate in transplant patients with CMV infection was achieved with administration of valganciclovir. In the patients with viremia, the mean time from onset of therapy to antigen negativity was 9.7 days (range, 4-22 days) (ICAAC V-285, IDSA 366).

Two cases of fatal fulminant hepatic failure in allogeneic bone marrow recipients due to adenovirus are described. A retrospective analysis of allogeneic HSCT recipients with disseminated adenovirus infection found that 75% of those treated with cidofovir died, while 83% of those untreated did so, a difference that was not significant. Cidofovir administration was associated with nephrotoxicity in 83% of recipients. The in vitro susceptibility of adenovirus to ribavirin was highly dependent on viral genogroup, with isolates of genogroups A, B, D, and E all being resistant and those of genogroup C being inhibited by the drug (IDSA 370, ICAAC K-1375, V-282).

BK viruria was present in 13% of nonrenal solid organ transplant recipients with unexplained chronic renal disease (IDSA 372).

Hypogammaglobulinemia occurred in 61% of nonmyeloablative allogeneic peripheral stem cell transplant recipients at a mean time of 2.5 months for the first low IgG level and 5.4 months for its nadir. It was strongly associated with the development of complete chimerism by 4 months post-transplantation (IDSA 400).

Geographic Medicine

Bacteria

Bartonella bacilliformis

B bacilliformis infection is endemic and previously believed to be limited to high-altitude river valleys of Peru, Columbia, and Ecuador. The first identification of this infection in the Peruvian Amazon involved 8 individuals with fever and 1 with skin lesions. All were blood-smear positive for B bacilliformis (ASTMH 163).

Leptospira

Ciprofloxacin, moxifloxacin, levofloxacin, and gatifloxacin were each much more potent on a weight basis than either penicillin G or doxycycline against 26 serovars of Leptospira (IDSA 232).

A retrospective review of 483 patients with severe late-stage leptospirosis found that administration of even a single dose of penicillin was independently associated with improved survival and that there was a 30% reduction in mortality with each cumulative daily dose given. This favorable effect was greatest when the antibiotic was administered during the first 3 days of hospitalization (IDSA 329).

Rickettsia

Of 743 patients with undifferentiated febrile illness in rural Thailand, 21% were found to have dengue, 14% had murine typhus, 10% had spotted fever group rickettsial infection, and 6.2% had leptospirosis (ICAAC L-18).

In Korea, 70 patients with mild scrub typhus were randomly assigned to treatment with a single 500-mg dose of azithromycin or to 1 week of 200-mg doxycycline daily, with equivalent results. The investigators note that doxycycline-resistant O tsutsugamushi may be seen in Korea (ICAAC L-182).

Blood- and Tissue-Dwelling Nematodes

Filaria

An epidemiological survey identified a number of villages in the rain forest of southwestern Cameroon where Onchocerca volvulus, Loa loa, and Mansonella perstans were all present (ASTMH 179).

Identification of filarial nests by observation of typical filarial movement—the filarial dance sign—on scrotal ultrasound examination is well described. This useful finding is not, however, confined to women. Filarial nests were identified by ultrasound detection of the filarial dance sign in 35 microfilaremic women in Ghana. The filarial dance sign was detected in various anatomic sites, including lymph nodes, breast, axilla, uterus, groin, and thigh muscles in half of the patients (ASTMH 132).

WHO recommends the combination of albendazole and diethylcarbamazine (DEC) in the treatment of lymphatic filariasis in areas where onchocerciasis and loasis are not endemic. A study in Papua New Guinea found that the combination was superior to DEC alone in clearing of microfilaremia. The addition of albendazole to ivermectin monotherapy in a mass treatment campaign in Nigeria was associated with a significant decrease in larval infection rates in anopheline mosquitoes, presumably as a consequence of improved suppression of nocturnal bancroftian microfilaremia in infected individuals (ASTMH 192, 181).

With the aim of eliminating Wolbachia endobacteria, a symbiont necessary for filarial reproduction, 59 Ghanians were treated with doxycycline for 6 weeks. Treatment resulted in a > 95% depletion of Wolbachia within microfilaria and a 99% reduction of microfilariae after 12 months. Scrotal ultrasound also demonstrated a 99% reduction in worm nests. In addition, an 8-week course of doxycycline resulted in a 50% reduction in microfilaremia at 3 months and "an almost complete absence" of circulating microfilariae at 6-12 months in Tanzania (ASTMH 133, 134).

 

Blood- and Tissue-Dwelling Protozoa

Babesia

Of 57 blood donors found to be seropositive for Babesia microti, 15 (26%) were found to be parasitemic, but parasitemia was subsequently undetectable in all by 4 months. Eight patients with babesiosis, including 3 with severe disease, were successfully treated with atovaquone plus azithromycin (ASTMH 357, IDSA 756).

Leishmania

Two patients with relapsed cutaneous leishmaniasis due to L braziliensis were successfully treated with liposomal amphotericin B (IDSA 754).

Malaria

A postmarketing surveillance report of Malarone™ (atovaquone/proguanil) use indicated that, as of April 2003, approximately 1.28 million prescriptions had been issued, with 48 reports of failure of prophylaxis and 15 reports of failure of treatment. There have been no reports of documented resistance in cases of failure of prophylaxis, but 5 cases of treatment failure were caused by plasmodia with mutations in codon 286 of the cytochrome b gene (ASTMH 245).

Some "prophylaxis failures" are bogus. A questionnaire survey of university staff and students who traveled to Ghana found that only 14 of 25 (56%) reported complete adherence to their prescribed malaria chemoprophylaxis. During the trip, 6 of 13 who sought medical care because of a febrile illness were told, based on microscopy, that they had malaria and were treated. Upon return to the United States, all 5 who were tested were found to have negative indirect fluorescent antibody tests for all human Plasmodium species, indicating that the diagnoses had been incorrect (ASTMH 57).

An analysis of data from the GeoSentinel surveillance network found that the most frequent specific diagnosis among febrile returned travelers was malaria, occurring in 670 of 4501 (14.9%). No specific diagnosis was reached in 20.3% (ASTMH 774).

The Binax NOW ICT Malaria Test™ was evaluated in Toronto in 256 febrile returned travelers. Compared to PCR, it had 94-96% sensitivity in the detection of pure or mixed P falciparum infections, as well as 87% sensitivity in pure P vivax infections and 62% for pure P ovale and P malariae infections. With a prevalence of malaria in the study group of 15%, the positive predictive values for P falciparum and non-P falciparum infections were 90% and 88%, and the negative predictive values were 98% and 94%, respectively. Separately, a comparison of the Binax NOW ICT Malaria Test™ and the OptiMAL rapid malaria test found that, while the former only performed well when the parasite count was > 1%, the latter did so at counts > 0.1% (ASTMH 250, 260).

Asymptomatic P falciparum parasitemia was detected in 17% of children in Kampala by microscopy and in 36% by PCR. PCR also found P ovale in 19%, P vivax in 7%, and P malariae in 4%. G6PD deficiency was associated with protection from clinical malaria in children and young adults in Mali (ASTMH 455, 628).

A 6-dose regimen of Co-Artemether™ (artemether/lunefantrine) was administered to 309 children in Kenya, Nigeria, and Tanzania with acute uncomplicated malaria due to P falciparum. The median time to defervescence was approximately 8 hours, and the time to parasite clearance was 24-36 hours. The 28-day cure rate was approximately 95%. Treatment was well tolerated, although 4-5% had QTc prolongation > 60 msec (ASTMH 37, 38).