Infectious Disease
July 15, 2002
Editor’s Note: In this feature, brief items, primarily gleaned from abstracts or articles in journals and other resources not commonly perused by most US Infectious Disease physicians, will be presented, usually without comment. —Stan Deresinki, MD, FACP
| Musculoskeletal Infections |
Management of Sternoclavicular Joint Infections
Simple drainage and debridement was associated with relapse in 5 of 6 patients leading the (surgical) authors to conclude "Aggressive surgical management including resection of the sternoclavicular joint and involved ribs with pectoralis flap closure would appear to be the preferred treatment for all but the most minor infections" (Song HK, et al. Ann Thorac Surg. 2002;73:427-431).
| Respiratory Infections |
Over-the-Counter Cough Medicines
A systematic review of randomized controlled trials found no evidence for efficacy of over-the-counter cough medicines, including antihistamines, antitussives, expectorants, and various combinations (Schroeder K, Fahey T. BMJ. 2002;324:329).
Etiology of Persistent Cough
PCR or culture evidence of M pneumoniae infection was found in respiratory specimens in 0.8% of 491 adolescents and adults with cough of at least 5 days duration; C pneumoniae was not found (Wadowsky RM, et al. J Clin Microbiol. 2002;40:637-640).
Nasopharyngeal Picornavirus in the Absence of Respiratory Symptoms
Picornavirus RNA was detected in nasopharyngeal aspirates of 29% (18% rhinovirus, 11% enterovirus) of 107 children without respiratory symptoms admitted for elective surgery, including 45% with past or recent respiratory symptoms and 20% without. Coronavirus RNA was not detected in any of the samples (Nokso-Koivisto J, et al. J Med Virol. 2002;66:417-420).
Influenza Vaccination in Lung Transplant Recipients
Lung transplant recipients demonstrated impaired serological responses to influenza vaccination when compared to healthy controls (Mazzone PJ, et al. Eur Respir J. 2001;18:971-976).
Zanamivir for Influenza after Allogeneic Stem Cell Transplantation
Zanamivir was administered by inhalation to 7 allogeneic stem cell recipients with influenza A or B virus infection with continued dosing until cessation of viral excretion. The drug was well tolerated and all 7 patients survived (Johny AA, et al. Bone Marrow Transplant. 2002;29:113-115).
Antibiotic Susceptibility of Respiratory Tract Anaerobes and B fragilis
Gatifloxacin inhibited 99% of 208 pulmonary anaerobic isolates, as well as an additional 30 isolates of B fragilis at 4 mg/mL and 97% at 2 mg/mL. One strain (3.3%) of B fragilis was resistant to 4 mg/mL. Resistance to clindamycin was detected in 5% of B fragilis, 21% of B fragilis group spp., and 20% of Clostridium spp. other than C difficile, C perfringens, or C ramosum. All isolates were susceptible to imipenem (Wexler HM, et al. Anaerobe. 2001;7:285-289).
Fluoroquinolone Resistance in Pneumococci in the United States
There was no significant change in fluoroquinolone resistance was found in 4650 US isolates of S pneumoniae over the 5 years ending December 31, 2000. The overall rank order of activity was moxifloxacin > gatifloxacin > levofloxacin = ciprofloxacin, with respective MIC90s of 0.25, 0.5, 1, and 2 mg/mL. Forty-nine of 164 (30%) unique isolates examined had at least 1 mutation in the QRDRs of one or both target topoisomerase genes, with two thirds of these being mutations in the parC locus alone. It was estimated that 0.3% of all isolates had mutations in both the parC and gyrA loci. Isolates with only parC mutations were, in general, resistant to ciprofloxacin alone, while those with mutations in both genes were resistant to all tested fluoroquinolones (Brueggemann AB, et al. Antimicrob Agents Chemother. 2002;46:680-688).
S pneumoniae & Susceptibility to Ceftriaxone
The NCCLS has increased the MIC interpretive break points of ceftriaxone and cefotaxime for nonmeningeal isolates of S pneumoniae. The effect of this change on the reinterpretation of susceptibility to ceftriaxone on 9863 isolates was an increase in the proportion deemed susceptible from 82.7% to 95.9%, and decreases in those judged intermediate from 13.2% to 3.1%, and as resistant from 4.1% to 1.0% (Sahm DF, et al. J Clin Microbiol. 2002;40:669-674).
Acinetobacter Throat Colonization and Community Acquired Pneumonia
Acinetobacter infection was previously reported to cause 10% of cases of community acquired pneumonia (CAP), as well as 20% of deaths from bacteremic CAP in tropical northern Australia with the majority occurring during the wet season in alcohol abusers. In this study, A baumanii was detected in the throats of 10% of community residents with excess alcohol intakes during the wet season (Anstey NA, et al. J Clin Microbiol. 2002;140:20-26).
Inhaled Tobramycin in Cystic Fibrosis
Analysis of several clinical trials found that cyclical administration of inhaled tobramycin to patients with cystic fibrosis was associated with improvement in pulmonary function persisting for at least 92 weeks of therapy and that this improvement correlated strongly with the reduction in density of P aeruginosa in sputum (Moss RB. Chest. 2002;121:55-63).
The Value of Diagnostic Thoracentesis in MICU Patients
Analysis found that 113 of 1351 (8.4%) MICU patients had a pleural effusion. Eighty two (72.5%) underwent thoracentesis: 24.4% had a transudative effusion, 32.9% had a exudates not due to infection while 42.7% had infectious exudates (60% parapneumonic effusion, 40% empyema). Thoracentesis yielded improvements in the diagnosis and/or treatment of 46 (56%) patients (Fartoukh M, et al. Chest. 2002;121;178-184).
| Nervous System Infections |
Epidemic Enterovirus 71
Evaluation of 90 patients with infection by enterovirus 71 during an epidemic in Taiwan found a case fatality rate of 12% (4 of 33) in those with CNS involvement and 0% in the remainder. Brain MRI demonstrated high intensity T2-weighted signal in 6 of 11 patients (Li CC, et al. Scand J Infect Dis. 2002; 34:104-109).
Post-MMR Aseptic Meningitis and Mumps
Evaluation of 2 mass campaigns of immunization with MMR (Leningrad-Zagreb mumps strain) in Brazil found an excess number of cases of aseptic meningitis and of mumps in the ensuing 3 weeks. The estimated incidence of vaccine-related meningitis was 1 in 6199 to 19,247 vaccine doses while that of vaccine related mumps was 1 in 300 doses (DaCunha SS, et al. Vaccine. 2002;20:1106-1112).
| HHV-6 and CNS Infection |
A 3-week-old afebrile infant had serological and PCR evidence of primary HHV-6 infection, adding to the evidence of the neuropathogenic potential of this virus (Zerr DM, et al. J Med Virol. 2002;66:384-387). A case of fatal multifocal meningoencephalitis believed due to HHV-6 and occurring in an apparently immunocompetent adult is described. (Beovic B, et al. Scand J Infect Dis. 2001;33:942-944).
HHV-6, HHV-7, and Influenza-Associated Encephalopathy
Eight Japanese children with influenza virus infection had either encephalopathy or complicated febrile convulsions. While examination of CSF by PCR revealed no evidence of influenza DNA, HHV-6 DNA was detected in 2 and HHV-7 DNA in 3 (Sugayua N, et al. Clin Infect Dis. 2002;34:461-466).
HHV-7 Encephalitis
An 8-year-old girl developed fatal encephalitis on day 41 after peripheral blood stem cell transplantation for relapsed ALL. She had received intrathecal chemotherapy on day 30. HHV-7 DNA was detected in CSF and brain stem tissue samples (Chan PKS, et al. J Med Virol. 2002;66:493-496).
Nipah Virus Infection
The mean incubation period in 103 patients in Malaysia, 78% of whom worked on pig farms with Nipah virus infection was 10 days. Initial symptoms were flu-like and nonspecific, with progression to deteriorating consciousness in the most severe cases, often associated with autonomic disturbances and myoclonic jerks. The mortality rate was 41%; 40% fully recovered while the remaining 19% survived with mostly mild neurological abnormalities (Chong HT, et al. Can J Neurol Sci. 2002;29:83-87).
Progressive Encephalitis in Patients with Primary Immunodeficiency Receiving IVIG
Fourteen patients with a variety of primary immunodeficiency diseases who had received IVIG for a mean duration of 6.5 years developed progressive neurodegeneration with nonspecific encephalitis of etiology. Among the proposed causes was a possible complication of long-term IVIG therapy (Ziegner UHM, et al. Clin Immunol. 2002;102:19-24).
Enhanced CNS Viral Invasion & Exposure to Inhalational Anesthetics
Studies using a murine model found that exposure to the inhalational anesthetics, halothane and nitrous oxide, allowed brain invasion by an attenuated strain of West Nile virus, probably by increasing access to the central nervous system (Katz Y, et al. J Med Virol. 2002; 66:567-570).
Cephalic Tetanus from Rooster Pecking
A woman developed cephalic tetanus after being pecked on the face by a rooster (Kara CO, et al. Scand J Infect Dis. 2002;34:64-66).
Pneumococcal Meningitis
The overall in-hospital mortality in 80 adults with severe pneumococcal meningitis was 25%; only 1 of the 17 (6%) infected with penicillin nonsusceptible strain died. Independent risk factors associated with death were the presence of thrombocytopenia, arterial pH > 7.47, and the need for mechanical ventilation. The administration of dexamethasone may have been protective in this retrospective study (Auburtin M, et al. Am J Respir Crit Care Med. 2002;165:713-777).
Deafness in the Meningitis Belt
It was estimated that meningococcal meningitis causes approximately 10,000 cases of deafness in sub-saharan Africa each year (Hodgson A, et al. Int J Epidemiol. 2001;30:1440-1446).
Cerebral Melioidosis
All 5 patients with cerebral infection with Burkholderia pseudomallei survived after surgical drainage and therapy with either ceftazidime or imipenem. Four of the 5 had radiographic evidence of paranasal sinusitis (Chadwick DR, et al. Trans Royal Soc Trop Med Hyg. 2002;96:72-76).
Pituitary Mycobacterial Infection
A 32-year-old woman with diabetes insipidus and amenorrhea for 6 months and fever and headaches for 19 days was found to have a pituitary mass with caseating granulomas in which M malmoense DNA was detected by PCR. There was no detected evidence of mycobacterial infection elsewhere (Florakis D, et al. Clin Endocrinol. 2002;56:123-126). A 32-year-old woman presenting with headache and amenorrhea was found to have hypopituitarism due to a pituitary tuberculoma (Paramo C, et al. Infection. 2002;30:35).
| Mycobacterial Infection |
Endogenous Reactivation of M tuberculosis After 33 Years
Comparison of DNA from clinical isolates of M tuberculosis found apparent identity with DNA of isolates between father and son that had been obtained 33 years previously (Lillebaek T, et al. J Infect Dis. 2002;185:401-404).
Pancreatic TB
Two patients with pancreatic tuberculosis presenting as multicystic masses are described (Franco-Paredes C, et al. Amer J Med Sci. 2002;323:54-58).
TB & IgA Nephropathy
A 35-year-old woman had resolution of IgA nephropathy after treatment of pleural tuberculosis (Matsuzawa N, et al. Clin Nephrol. 2002;57:63-68).
INH Prophylaxis in Corticosteroid Treated SLE Patients at High Risk of Tuberculosis
INH prophylaxis for 1 year in Indian patients with SLE receiving long-term corticosteroid therapy was well tolerated (hepatotoxicity and peripheral neuropathy each occurred in 1 of 97 patients) and was associated with an apparent reduction in the incidence of active tuberculosis, when compared to historical experience (Gaitonde S, et al. Ann Rheum Dis. 2002;61:251-253).
Tuberculosis Transmission Via Organ Transplant
Two cases of apparent transmission of tuberculosis by a transplanted organ are described (Graham JC, et al. J Infect. 2001;43:251-254).
Chlorine Disinfection of "Rapid Growers" in Water
M fortuitum and M chelonae were hundreds of times more resistant to chlorine than E coli (LeDantec C, et al. Appl Environ Microbiol. 2002;68:1025-1032).
Immune Status of Lepromatous Leprosy Patients After Successful Therapy
All 19 patients with treated lepromatous leprosy and a prolonged period of smear negativity remained anergic to Mitsuda lepromin and only 2 demonstrated in vitro lymphocyte proliferation in response to antigens of M leprae (Joshi B, et al. Int J Lepr Other Mycobact Dis. 2001;69:195-203).
| Viral Hepatitis |
Hepatitis A Vaccination
All 25 subjects given a booster dose of Havrix 4-6 years after a single primary dose demonstrated a significant anamnestic response (Iwarson S, et al. Scand J Infect Dis. 2002;34:110-111).
Transiently Positive Tests for HBsAg After HBV vaccination
The recently released Abbott/Murex GE 34/36 detected HBsAg in 7 of 8 volunteers on the third day after hepatitis B vaccination; one subject was still positive at day 5. Two older tests, the Abbott Auszyme and the Ortho HBsAg-3, did not detect HBsAg in these subjects (Dow BC, et al. Vox Sanguis. 2002;82:15-17).
HCV Transmission by Surgery
Phylogenetic analysis of the hypervariable region 1 found evidence of transmission of HCV from an infected orthopedic surgeon to a patient (Pingel S, et al. J Med Virol. 2002;66:472-480).
Interferon Gamma & HCV
Interferon gamma inhibits protein synthesis and RNA replication of subgenomic and genomic HCV replicons in vitro (Frese M, et al. Hepatology. 2002;35:694-703).
Another Way HCV Evades Immune Destruction
Ligation of the HCV receptor, CD81, by either the major envelope protein of HCV or by ant-CD81 antibody, blocks NK cell activation, cytokine production, cytotoxic granule release, and proliferation, apparently by blocking tyrosine phosphorylation (Crotta S, et al. J Exp Med. 2002;195:35-41).
Hepatic HCV RNA
The concentration of HCV RNA in liver prior to therapy correlated positively with serum HCV RNA concentration and negatively with, among other factors, ALT, the duration of infection, the degree of hepatic injury, and the Knodell fibrosis score. In patients who had both pre- and posttherapy liver biopsies, the change in hepatic HCV RNA correlated with the change in the histologic activity index. Also, 98% of 400 sustained virologic responders had undetectable hepatic HCV RNA (McHutchison JG, et al. Hepatology. 2002;35:688-693).
Quality of Life After Successful Treatment of Chronic HCV Infection
Sustained virological response to treatment in HCV- infected patients was associated with improved quality of life regardless of the severity of liver disease (Bernstein D, et al. Hepatology. 2002;35:704-708).
HIV/HCV Coinfection: Response to Therapy
Although the sustained virological response rate to interferon alpha therapy of HCV infection was significantly impaired in the presence of HIV coinfection (29.8% vs 6.2%), the rate of histological response was not (40.6% vs 36.2%). Histological response was also seen in 25% of virological nonresponders regardless of the presence or absence of HIV coinfection (DiMartino V, et al. AIDS. 2002;16:441-445).
| Mycoses |
Oral and Vaginal Therapy Appear Equally Efficacious in the Treatment of Uncomplicated Vulvovaginal Candidiasis
A systematic review of published reports found no apparent difference in the relative efficacy of oral and intravaginal therapy of uncomplicated vulvovaginal candidiasis, although preferences, when expressed, commonly favored the former route (Watson MC, et al. BJOG. 2002;109:85-95).
Candida africana?
An atypical strain of Candida was isolated from patients in Madagascar, Angola, and Germany. Tietz and associates suggest that it may represent a new species and propose the name Candida africana (Tietz HJ, et al. Mycoses. 2001;44:11-12).
SICU Outbreak of Hansenula Infections
Eight cases of infection due to Hansenula anomala occurred over a 5-month period in a surgical ICU; no source was detected. Only the duration of blood alkalosis was found to be an independent risk factor on multivariate analysis (Kalenic S, et al. Eur J Epidemiol. 2001;17:491-496).
Cryptococcal Meningitis in AIDS
One hundred-six Thai AIDS patients with cryptococcal meningitis were treated with amphotericin B 0.7 mg/kg/d followed by an orally administered azole. The geometric mean viable CSF colony count at baseline was 31,000/mL; this level declined monoexponentially during therapy with an elimination half-life of 4 days. The cumulative mortality rates at 2 weeks, 4 weeks, and 1 year were, respectively, 16%, 24%, and 76%. Late mortality was associated with delayed CSF yeast clearance (Pitisuttithum P, et al. J Infect. 2001;43:226-233).
Job’s Syndrome, Generalized Lymphadenopathy, and Trichonosporosis
Trichosporon asahii was the cause of generalized lymphadenopathy in a child with Job’s syndrome (Chakrabarti A, et al. Med Mycol. 2002;40:83-86).
Aspergillus: Increasing Frequency but Stable Susceptibility to Antifungals
There was a 2.5-4.5 fold yearly increase in the number of isolations of Aspergillus spp. at the Detroit Medical Center from 1994 through 1999, but there has been continued stable susceptibility to amphotericin B and to the azoles. The MIC 90 for amphotericin B was 0.5 mg/mL, while for itraconazole, voriconazole and posaconazole it was 1.0, 0.5, and 0.35 mg/mL, respectively (Chandrasekar PH, et al. Diagn Microbiol Infect Dis. 2001;41:211-214).
Chronic Necrotizing Pulmonary Aspergillosis
Ten men with pneumoconiosis had superimposed chronic necrotizing aspergillosis radiographically characterized as parenchymal infiltrates with cavities (many with mycetoma), mostly involving the upper lobes. Disease progression was slow (Kato T, et al. Chest. 2002; 121:118-127).
Lung and Heart/Lung Transplantation in Patients with Pulmonary Mycetoma
Nine of 303 (3%) explanted lungs from patients undergoing lung or heart/lung transplantation contained mycetoma. Aspergillus was recovered from 5 patients pretransplant and from 5 posttransplant. All patients were given antifungal therapy after transplantation and all of the "medium-term survivors received lengthy therapy with inhaled and systemic amphotericin B and itraconazole before and after transplantation" (Hadjiliadis D, et al. Chest. 2002;121:128-134).
Late Aspergillosis After Allogeneic Bone Marrow Transplantation
None of 149 autologous bone marrow recipients developed invasive aspergillosis, while 15.1% of 93 allogeneic recipients did so. No new cases occurred prior to engraftment and the median time to occurrence was 92 days posttransplantation. Identified risk factors were prolonged (> 21 days) high-dose (> 1 mg/kg/d) corticosteroid therapy and posttransplant CMV infection (Grow W, et al. Bone Marrow Transplant. 2002;29:15-19).
Malassezia Colonization in Neonates & Association with Neonatal Acne
A prospective study found that skin colonization with Malassezia spp., esp. M sympodialis, and M globosa, begins at birth and increases in frequency over the next weeks. M sympodialis was associated with neonatal acne (Bernier V, et al. Arch Dermatol. 2002;138:215-218).
| Geographic Medicine |
Helminthiasis and Cerebral Malaria May Not Go Together
The presence of helminth infestation and of malnutrition were independently associated with protection from cerebral malaria in Thailand (Nacher M, et al. Ann Trop Med Parasitol. 2002;69:5-13).
Onchocerciasis & Wolbachia
Studies in a murine model of onchocerciasis demonstrated that the inflammatory response induced in the cornea is due to the endosymbiont bacterium, Wolbachia, rather than Onchocerca per se (SaintAndre AV, et al. Science. 2002; 295:1892-1895).
Therapy of Experimental Leptospirosis
An animal model of infection with Leptospira interrogans serovar icterohaemorrhagiae with quantitative PCR monitoring found that doxycycline therapy was more effective than either ampicillin or ofloxacin. (Truccolo J, et al. Antimicrob Agents Chemother. 2002; 45:848-853).
African Tick Typhus in Travelers
Thirteen of 152 (8.6%) first-time Norwegian travelers returned from sub-Equatorial Africa and had serological evidence of exposure to Rickettsi africae. Eight of the 12 (62%) reported symptoms consistent with African tick bite fever. Hunting and staying in a rural area were risk factors for seropositivity (Jensenius M, et al. Scand J Infect Dis. 2002;34:93-96).
Pediatric Murine Typhus
Nine children in Crete with murine typhus presented with prolonged fever, hepatosplenomegaly, and thrombocytopenia; 5 had skin rash. Aseptic meningitis and illness resembling Kawasaki Disease were also observed (Bitsori M, et al. Acta Pediatrica. 2002;91:59-61).
A New Hemorrhagic Fever Virus
A novel reassortant Bunyavirus was recovered from 2 patients with hemorrhagic fever in East Africa. The name Garissa virus is proposed (Bowen MD, et al. Virology. 2001;291:185-190).
| Antibiotic Therapy & Resistance |
Penicillin-Resistance in Alpha-Hemolytic Streptococci
Only 8 of 33 (21%) of bloodstream isolates of alpha-hemolytic streptococci in pediatric cancer patients were susceptible to penicillin, while 42% were intermediate and 37% were resistant (LB Bruckner, et al. J Pediatr. 2002;140:20-26).
Fluoroquinolones and Resistance Mutation Frequency in the Pneumococcus
The frequency of selection of first-step topoisomerase mutants in S pneumoniae was 1000 times lower for moxifloxacin than for levofloxacin, a difference that was, however, lost with regard to second step mutants (Li X, et al. Antimicrob Agents Chemother. 2002; 46:522-524).
Penicillin Production by Fungi Growing on Food Products
Penicillium chrysogenum and Penicillium nalgiovense, known to be penicillin producers, are commonly isolated from fermented and cured meat products and P nalgiovense has been shown to produce penicillin while growing on the surface of meat and to secrete it into the medium. Penicillium griseofulvin also produces penicillin. These findings have implications with regard to penicillin allergy and the development of antibiotic resistance (Laich F, et al. Appl Environ Microbiol. 2002;68:1211-1219).
Emergence of Fluoroquinolone Resistance in Chickens Given Fluoroquinolones
Fluoroquinolone (sarafloxacin or enrofloxacin) administration to Campylobacter jejuni infected chickens for only 5 days was associated with the development of ciprofloxacin resistance in this gastrointestinal pathogen (McDermott PF, et al. J Infect Dis. 2002; 185:837-840.
QD Vancomycin
A prospective comparison of patients given vancomycin either q.24.h or q.12.h found no significant difference in clinical response or in nephrotoxicity, ototoxicity, or the occurrence of "red man" syndrome (Cohen E, et al. Antimicrob Agents Chemother. 2002;49:155-160).
Antibiotic Prophylaxis for TURP
A meta-analysis found that antibiotic prophylaxis, especially of short duration, significantly reduced the risk of bacteriuria and septicemia in men with preoperative sterile urine undergoing transurethral prostatic resection (Berry A, Barratt A. J Urol. 2002;167:571-577).
Ciprofloxacin & Achilles Tendinopathy
Twenty-two of 101 lung transplant patients responding to a questionnaire reported suffering either Achilles tendonitis (16) or rupture (6) and this was significantly associated with ciprofloxacin use, occurring in 28% of recipients of this drug (Chhajed PN, et al. European Resp J. 2002;19:469-471).
Discontinuation of Empiric Antibacterial Therapy in Febrile Neutropenia
Empiric antibiotic therapy was safely discontinued during 84 episodes of febrile neutropenia in children with ALL that were classified as FUO after at least 72 hours of treatment and 24 hours of euthermia regardless of ANC (Lehrnbecher T, et al. Infection. 2002;30:17-21).
| HIV/AIDS |
HAART and HIV-Associated Renal Disease
A retrospective analysis of HIV-infected patients referred to a renal clinic between 1996 and 2000 found HAART was associated with improved outcome of renal disease (Cosgrove CJ, et al. Amer J Med Sci. 2002; 323:102-106).
Impaired Olfaction in HIV Infection
100% of 38 HIV-infected patients representing the spectrum of disease, none of whom had severe cognitive impairment, had olfactory impairment (Mueller C, et al. Acta Otolaryngol. 2002;122:67-71).
Combined Treatment of Genital Warts in HIV Infected Patients
Combined treatment of genital warts in HIV-infected patients with excisional electrocautery and topical 1% cidofovir gel was more effective than treatment with either modality alone (Orlando G, et al. AIDS. 2002; 16:447-450).
HSV2 Infection and Risk of HIV Infection
Both prevalent and incident HSV2 infection was associated with a significantly increased rate of HIV seroconversion in men and women in Tanzania (Rodriguez M, et al. AIDS. 2002;16:451-452).
AIDS Related NHL in HAART Responders
Twelve of 34 (35%) who developed non-Hodgkin’s lymphoma while receiving triple antiretroviral therapy did so at a time when their plasma HIV RNA was < 400 copies/mL and their median CD4 cell count was 301 cells/mm3 (range, 46-667 cells/mm3) (Vilchez RA, et al. AIDS Res Hum Retrovir. 2002;18:237-242).
Beware Bad Genotyping
A proficiency study using a defined panel of HIV isolates found extensive interlaboratory variation in the quality of genotyping with a significant underestimation of the presence of resistance associated mutation (Schuurman R, et al. AIDS Res Hum Retroviruses. 2002;18:243-248).
Hepatotoxicity During Antiretroviral Therapy
A retrospective analysis found that coinfection with hepatitis virus coinfection, ritonavir administration, and, in patients with HCV coinfection, failure of antiretroviral therapy were risk factors for hepatoxicity during antiretroviral therapy (Aceti A, et al. J Acquir Immune Defic Syndr. 2002;29:41-48).
D30N & L90M are Mutually Exclusive (Almost)
The emergence of the "nelfinavir signature" D30N mutation is strongly suppressed in the presence of the L90M mutation, which is associated with resistance to several PIs, including nelfinavir. This suggests that D30N and L90M are mutually exclusive during HIV evolution (Sugiura W, et al. Antimicrob Agents Chemother. 2002; 46:708-715).
NRTI Effects on Mitochondria
The relative potencies of inhibition of mitochondrial DNA by NRTIs was zalcitabine > didanosine > stavudine > zidovudine > lamivudine = abacavir = tenofovir. Concentrations of tenofovir associated with therapeutically relevant plasma levels did not cause mitochondrial toxicity in vitro (Birkus G, et al. Antimicrob Agents Chemother. 2002;46:716-723).
Therapeutic Drug Monitoring
An international quality control program found great variability among laboratories in the measurement of plasma concentrations of antiretroviral drugs (Aarnoutse RE, et al. Antimicrob Agents Chemother. 2002;46:884-886).
Abnormal Auditory Evoked Potentials in HIV-Infected Patients
Brainstem auditory evoked response was abnormal in a group of HIV-infected patients, both with and without AIDS, when compared to non-HIV-infected controls (ReyesContreras L, et al. Arch Med Res. 2002;33:25-28).
Acute Hepatic Failure & Antiretroviral Therapy
Five of 6 HIV-infected patients with acute liver failure died. While only 2 had had AIDS defining illness, all had received antiretroviral therapy (median duration, 12.5 months) with a median time since the introduction of a new antiretroviral of 8 weeks (range, 2-12 weeks). Evidence of mitochondrial toxicity was detected in a liver biopsy specimen in only 1 patient (Clark SJ, et al. J Hepatol. 2002;36:295-301).
Antiangiogenic Activity of Protease Inhibitors
Indinavir and saquinavir each directly blocked development and induced regression of KS-like lesions promoted by human KS cells in nude mice apparently as a result of anti-angiogenic activity (Sgadari C, et al. Nat Med. 2002;8:225-232).
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