Special Supplement: Infectious Disease
Supplement
Infectious Disease
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
RESPIRATORY INFECTIONS
Aspiration Pneumonia and the Elderly
Examination of Medicare discharge data for elderly patients from 1991 through 1998 found that annual hospitalizations for aspiration pneumonia almost doubled, increasing by 93.5% (Baine WB, et al. Am J Public Health. 2001;91:1121-1123).
Does Sputum Induction Improve the Quality of Sputum Specimens for Routine Bacteriology? Answer: Not if They Have a Productive Cough
One hundred twenty hospitalized patients with productive cough and a diagnosis of lower respiratory tract infection were randomized to provide a sputum specimen either spontaneously or after induction by untrained nurses with hypertonic saline. The quality of the specimens, as judged by the cellular content seen after Gram staining, did not differ between the 2 groups. It should be noted, however, that an earlier study (Respiration. 2000;67:173) in patients with a nonproductive cough found sputum induction to be of value (Chuard C, et al. Diagn Microbiol Infect Dis. 2001;39:211-214).
Plasma D Dimer, Pneumonia, and Pulmonary Embolism
Plasma D dimer levels were elevated in patients with community-acquired pneumonia, although not to levels associated with high probability of pulmonary embolism. Nonetheless, it is concluded that measurement of D dimer levels are "useless in the differential diagnosis" between pulmonary embolism and pneumonia (Castro DJ, et al. Respiration. 2001;68:371-375).
Unsustained Benefit of Macrolide Therapy in Patients with Asthma and Past Chlamydia pneumoniae Infection
In this study, 232 patients with asthma and serological evidence of C pneumoniae infection (IgG > 1:64 and/or IgA > 16) were randomized to receive either roxithromycin (150 mg qd) or placebo for 6 weeks. The roxithromycin group had a significantly greater improvement in their peak expiratory flow rate, but this benefit was not sustained, being nonsignificant at 3-month and 6-month examinations (Black PN, et al. Am J Resp Crit Care Med. 2001;164:536-541).
Fluoroquinolones and Legionella
In vitro susceptibility testing of 140 Legionella spp. isolates using BYE alpha broth found that trovafloxacin, levofloxacin, moxifloxacin, and ciprofloxacin had MIC90s ranging from 0.008 mg/mL to 0.06 mg/mL, while those of erythromycin and azithromycin were 0.5 mg/mL for each. The MIC90 for rifampin was 0.004 mcg/mL. The MBCs of the fluoroquinolones and rifampin were £ 4 ´ MIC, while for the macrolides it was < 8 × MIC. The duration of the postantibiotic effect ranged from 2.25 hours for the fluoroquinolones and rifampin, while it was 1.54 hours for erythromycin, and 1.65 hours for azithromycin. The use of a cell-free system in studies of this intracellular pathogen raises questions, however, regarding its relevance (Gomez-Lus R, et al. Int J Antimicrob Agents. 2001;18:49-54).
Pneumococcal Vaccination
A meta-analysis of 14 randomized trials involving 48,837 subjects found that pneumococcal polysaccharide vaccination is associated with a reduction in the incidence of definite and presumptive pneumococcal pneumonia of, respectively, 71% and 40%, while reducing mortality due to pneumonia by 32%. However, "no preventive effect was seen in the subgroup of patients 55 years or more, possibly due to a lack of statistical power." (Cornu C, et al. Vaccine. 2001;19:4780-4790.)
Zanamivir and Response to Influenza Vaccination
Zanamivir administration to healthy adults did not interfere with the antibody response to the H3N2 influenza A and the influenza B component of a trivalent vaccine, while the placebo group developed higher antibody titers to H1N1. Cox and colleagues suggest that, during an outbreak, zanamivir need be only administered for 12 days after vaccination (Cox RJ, et al. Vaccine. 2001;19:4743-4749).
GASTROINTESTINAL INFECTIONS
Ophthalomoplegia and Campylobacter
An association between Campylobacter jejuni infection and the development of Guillian-Barré and Miller-Fisher syndromes has been described. Kuroki and associates report 3 patients with idiopathic cranial polyneuropathy with predominant ocular involvement from whose stool C jejuni was isolated. Each had elevated serum anti-GQ1 antibodies that decreased rapidly at the time of clinical recovery (Kuroki S, et al. Pediatr Neurol. 2001;25:71-74).
Helicobacter pylori Infection is Associated with a Decreased Incidence of Erosive Reflux Esophagitis, While its Association with Gastric Cancer is Confirmed
H pylori infection may prevent reflux esophagitis by inducing hypoacidity. This appears to be especially true with regard to strains that have the cytotoxin associated gene (cagA). CagA+ strains have previously been associated with a reduced risk of esophageal adenocarcinoma. A meta-analysis found an estimated 5.9-fold relative risk of noncardia gastric cancer in association with H pylori infection (Koike T, et al. Gut. 2001;49:330-334; Yamaji Y, et al. Gut. 2001;49:335-340; Warburton-Timms VJ, et al. Gut. 2001;49:341-346; Webb PM, et al. Gut. 2001;49:347-353).
ENDOCARDITIS
Predictors of Recurrent Endocarditis After Valve Replacement Surgery
A retrospective review in Naples found that endocarditis recurred in 58 of 271 (22.5%) patients who had undergone replacement of a cardiac valve that had been or was infected. Variables associated with recurrence were surgery for prosthetic valve endocarditis, positive culture of the removed valve, and postoperative fever persisting for at least 7 days (Renzulli A, et al. Ann Thorac Surg. 2001;72:39-43).
Coagulase-Negative Staphylococci and Native Valve Endocarditis
Seven cases with histologically proven native valve endocarditis were seen at one institution over 10 years; all required valve replacement. While 4 patients had had central venous catheters and one had recently undergone surgery, 2 had no identifiable risk factors (Miele PS, et al. Am Heart J. 2001;142:571-576).
Nosocomial Bloodstream Infections (BSI) in Patients with Implantable Left Ventricular Assist Devices (LVAD)
In this study, 49% of 214 patients had BSI with an incidence of 7.9 per 1000 LVAD-days and 38% of the infections involved the device. Coagulase-negative staphylococci, S aureus, and Candida spp. were the most commonly identified pathogens (Gordon SM, et al. Ann Thorac Surg. 2001;72:725-730).
CENTRAL NERVOUS SYSTEM INFECTION
Rapidity of CSF Sterilization After a First Parenteral Dose of Antibiotic
The rapidity with which empiric antibiotic therapy may render CSF culture-negative was analyzed in 128 children with bacterial meningitis—30% of whom had their first LP after the initiation of parenteral antibiotics. Another 43% had LPs both before and after the initiation of therapy. Among 9 patients with meningococcal infection who received > 50 mg/kg of a third-generation cephalosporin, CSF was sterile in 3 within 1 hour, and all 9 were sterile within 2 hours (1 was sterile within 15 minutes). Among patients with pneumococcal infection, the first negative-CSF culture occurred at 4.3 hours and 5 of 7 were negative from 4 to 10 hours after initiation of parenteral antibiotics (Kanegaye JT, et al. Pediatrics. 2001;108:1169-1174).
Pyogenic Ventriculitis
The presence of ventricular debris, usually irregular in distribution and size, was present on CT and/or MRI of the brain in 16 of 17 (94%) of patients with pyogenic ventriculitis. Periventricular hyperintense signal and ependymal enhancement were also frequently observed (Fukui MB, et al. Am J Neuroradiol. 2001;22:1510-1516).
Cranial Subdural Empyema: Craniotomy is Better than a Burr Hole
Stepwise discriminant analysis of a retrospective cohort of patients with cranial subdural empyema found that craniotomy, rather than more limited surgical procedures, such as burr hole placement, found a significantly improved outcome when the former was performed (Nathoo N, et al. Neurosurgery. 2001;49:872-877).
Parvovirus B19 and Encephalitis
In what the authors indicate is a first, a previously healthy woman with clinical and serological evidence of parvovirus B19 infection developed encephalitis (Skaff PT, Labiner DM. Neurology. 2001;57:1336-1337).
SKIN AND SOFT TISSUE INFECTION
S aureus of Nose and Skin in Recurrent Skin Infections
Pairs of S aureus isolates obtained from the infection site and from the nares of 12 patients with chronic and recurrent skin infections were identical, both phenotypically (hemolytic activity, antibiotic resistance pattern, enterotoxin production, phage type) and genotypically (number of repeats in the X region of the spa gene, coa gene polymorphisms, PFGE macrorestriction analysis of chromosomal DNA) (Toshkova K, et al. FEMS Microbiol Lett. 2001;202:17-24).
Breast Abscess Management—Needle Aspiration
Thirty patients with 33 breast abscesses were treated with orally administered antibiotics and, instead of incision and drainage (I & D), by needle aspiration without ultrasound guidance. While 18 patients required only a single aspiration, 9 required multiple aspirations, and 6 (18%) required I & D (Schwarz RJ, Shrestha R. Am J Surg. 2001;182:117-119).
Imaging of Acute Deep Neck Infections
Forty-seven patients with proven neck infections underwent both CT and MRI with contrast. MRI was significantly better than CT in lesion conspicuity, determination of the number of anatomic spaces involved and extension, and determination of the source of infection. CT was somewhat better in the detection of intralesional gas and calcium (Munoz A, et al. J Comput Assist Tomogr. 2001;25:733-741).
VIRAL HEPATITIS
Havrix vs. VAQTQ
Volunteers were randomized to receive 2 doses of inactivated HAV vaccine: Havrix-Havrix, Havrix- VAQTA, VAQTA-Havrix, or VAQTA-VAQTA. All 4 regimens were immunogenic, but VAQTA-VAQTA yielded significantly higher antibody concentrations than Havrix-Havrix (Bryan JP, et al. Vaccine. 2001;19: 743-750).
Delayed Booster Dose of HAV Vaccine Works
Healthy adults were given their 2nd dose of VAQTA 6, 12, or 18 months after the initial dose with comparable results in each case (Hornick R, et al. Vaccine. 2001; 19:4727-4731).
HAV Vaccination in Liver Transplant Recipients—Not so Hot
Although HAV vaccination appeared safe in liver transplant recipients, only approximately one fourth of patients seroconverted (Arslan M, et al. Transplantation. 2001;72:272-276).
HCV Infection with Normal LFTs
Only 94 of 135 (69%) of 135 consecutive HCV antibody positive patients with persistently normal ALT had detectable HCV RNA in serum. Serum ALT was lower and liver histology was less severe in patients without detectable serum HCV-RNA. None of 12 serum HCV RNA-negative patients had detectable HCV RNA in liver biopsy specimens. During a mean follow-up of 3.6 years, serum HCV RNA remained undetectable and ALT remained normal in all who were so initially while all others remained HCV RNA positive and 21% of these had occasional slight increases in ALT. Liver histology remained stable in all who underwent rebiopsy (Martinot-Peignoux M, et al. Hepatology. 2001;34:1000-1005).
Hepatic HCV RNA
There was no correlation between the amount of hepatic HCV RNA in pretreatment liver biopsy samples and the severity of liver disease. Higher levels were found in patients infected with HCV genotype 1 and lower levels were seen in patients who proved to be sustained responders than in those without such a response. HCV RNA could not be detected in post-treatment liver biopsy samples of sustained responders (Gervais A, et al. J Hepatol. 2001;35:399-405).
HCV and Risk of Cirrhosis
A systematic literature review led to the conclusion that, for persons who acquire HCV infection in early adulthood, fewer than 10% are estimated to develop cirrhosis within 20 years. It was also concluded that previous higher estimates of risk (usually, approximately 20%) were the result of selection bias (Freeman AJ, et al. Hepatology. 2001;34:809-816).
Interferon Alpha Induction Followed by Combined Therapy for Infection with HCV Genotype 1
In a randomized trial examining higher dose interferon a for the first 14 weeks of therapy, and a combination treatment with ribavirin, no benefit was found for the participants as a whole. However, among patients infected with HCV genotype 1 treated with the highest induction dose (10 MU IntronA daily for 2 weeks followed by 10 MU qd for 10 weeks), sustained responses were almost twice as high as in those receiving lower induction doses (44.2% vs 28.6%, and 27.0%, P < 0.05). (Ferenci P, et al. Hepatology. 2001;34:1006-1001).
Retinopathy During Interferon a Therapy
Eight of 19 prospectively observed patients with chronic HCV infection receiving interferon a therapy developed transient asymptomatic retinopathy (Jain K, et al. Br J Ophthalmol. 2001;85:1171-1173).
Amantadine for HCV infection?
Two multicenter randomized trials failed to find any sustained benefit from the addition of amantadine to interferon a in the treatment of chronic HCV infection (Murray-Lyon L, et al. J Hepatol. 2001;35:512-516; Tabone M, et al. J Hepatol. 2001;35:517-521).
IL-12 for HBV/HCV Infection?
In 2 open-label multicenter trials, patients with chronic HCV infection (n = 60) and chronic HBV infection (n = 46) received recombinant human interleukin-12 (rHuIL-12) with minimal antiviral effect (Zeuzem S, Cerreno V. Antiviral Res. 2001;52:181-188).
Occult HBV Infection
Examination of 2565 Chinese patients, including patients with chronic hepatitis, cryptogenic cirrhosis, chronic renal failure on hemodialysis, and blood donors, found 51 (2.0%) with occult HBV infection (HbsAg-negative, HBV DNA-positive). Sequencing of the gene coding for the surface antigen found that 20 of 46 (43%) had one or more mutations in the major hydrophilic region of HbsAg. These results have important implications for blood screening (Hou JL, et al. Hepatology. 2001;34:1027-1034).
Combination Therapy for HBV Infection
In this study, 153 patients with chronic HBV infection were radomized to receive lamivudine with or without interferon a2b for 52 weeks with an additional 48 weeks follow-up. Sustained combination therapy was associated with improved HbeAg seroconversion (33% vs 15%; P = 0.014) and frequency of a 2 point or greater reduction in the hepatic inflammation score (46% vs 27%; P = 0.021) (Barbaro G, et al. J Hepatol. 2001; 35:406-411).
HBV, Interferon, and ALT Flares
A retrospective analysis of 121 patients and 42 untreated controls found that those who experienced an "ALT flare" during interferon alpha therapy were significantly more likely than those without a flare to have undetectable serum HBV DNA, as well as loss of serum HbeAg at the end of follow-up. Among those with high baseline serum HBV DNA, a severe flare was associated with an improved virological response. Multivariate analysis found that high baseline HBV DNA, high pretreatment ALT, and both moderate and severe ALT flare were independent predictors of a virological response (Nair S, Perrilo RP. Hepatology. 2001;34:1021-1026).
Triple Infection: HCV/HBV/HDV
Concurrent hepatitis D virus (HDV) infection suppresses hepatitis B virus (HBV) replication in dually infected individuals, sometimes to the extent that HBV surface antigen may become undetectable despite active disease. A study of patients dually infected with hepatitis C virus (HCV) and HBV has found that HCV has a similar effect. In triply infected (HCV/HBV/HDV) patients, HDV is the dominant virus with HCV and HBV replication inhibited (Jardi R, et al. Hepatology. 2001;34:404-410).
Acute Non-A-E Hepatitis
In this trial, 45 (85%) of 53 adult patients admitted to a Taiwan hospital with acute non-A-E hepatitis had severe disease (albumin < 3 g/dL, bilirubin > 15 mg/dL, or prothrombin time prolongation > 3 seconds) with 3% having fulminant hepatitis and 7% having developed chronic disease (Chu CM, et al. J Med Virol. 2001;65:296-300).
MYCOBACTERIAL INFECTIONS
BCG and PPD Boosting
Repeat tuberculin skin testing at 1 week in BCG-vaccinated hospital employees caused a booster effect that was maximal (mean, ± 7.8 mm induration) at 48 hours and then waned (Singh D, et al. Am J Resp Crit Care Med. 2001;164:962-964).
Diagnosis of TB by Direct Application of Gen-Probe
Six hundred sixty-three respiratory and 238 nonrespiratory specimens from 464 patients, 56 of whom had pulmonary and 19 extrapulmonary tuberculosis were examined directly using the upgraded Amplified Mycobacterium Tuberculosis Test kt (AMTD; Gen-Probe, Inc.) with the results compared to clinical and culture data. Using the traditional cutoff for a positive test, the sensitivity was 96.7% with smear-positive and 81.0% with smear-negative specimens, with an overall specificity of 93.0%. It was possible to adjust the cutoff, improving specificity without impairing the sensitivity of the test (Alcala L, et al. Diagn Microbiol Infect Dis. 2001;41:51-56).
Tuberculous Pleural Effusion
Measurement of the concentration of adenosine deaminase levels in pleural effusions has been touted as a means of diagnosis of a tuberculous etiology. In this study of 106 pleural fluid samples with a predominance of lymphocytes, but of nontuberculous etiology, only 3 (2.8%) false-positive results were found (Lee YGC, et al. Chest. 2001;120:356-361).
Cavitary Bronchiolitis Obliterans Mimicking Tuberculosis ("TB or not TB")
Two cases are described (Heller I, et al. Chest. 2001; 120:674-678).
Sea Urchin Granuloma and Mycobacterium marinum
Sea urchin granuloma is a chronic granulomatous reaction, histologically resembling sarcoid, occurring after injury by sea urchin spines, generally thought to be an allergic-type foreign body reaction. A group of Spanish investigators detected M marinum DNA in biopsy specimens from 7 of 35 (20%) patients. (Something learned along the way: the word urchin is derived from "ekhinos," the Greek word for hedgehog). (De La Torre C, et al. Br J Dermatol. 2001;145:114-116).
ANTIBIOTIC THERAPY AND ANTIBIOTIC RESISTANCE
Antibiotic Therapy—Some People Just Can’t Make Up Their Minds
In this study, 427 antibiotic regimens were administered to 119 patients with suspected serious infections during the first 72 hours after admission to a university affiliated municipal teaching hospital. Multiple antibiotic changes were made without apparent clinical or microbiological indications. By 72 hours, each patient had received a mean of 3.1 ± 1.3 different antibiotics; 40 patients had received from 4 to 7 different antibiotics (Lawrence C, et al. Am J Med Sci. 2001;322:61-67).
Macrolide Therapy and Resistance in Oral Flora
Azithromycin therapy in children with respiratory tract infections was associated with a significantly greater number (85%) harboring resistant oral aerobic bacterial flora persisting 6 weeks after therapy than was seen with erythromycin, clarithromycin, roxithromycin, or josamycin (Kastner U, Guggenbichler JP. Infection. 2001;29:251-256).
Fluoroquinolone Pharmacodynamics and S pneumoniae
Serum concentration-time profiles were simulated for qd administration of levofloxacin 500 mg & 750 mg, gatifloxacin 500 mg, moxifloxacin 500 mg, and femifloxacin 320 mg. Using the free (nonprotein bound) serum concentrations and the MICs of 307 clinical isolates of S pneumoniae, the proportion of pneumococcal isolates for which an AUIC (AUC24/MIC) > 30-50 was achieved was significantly inferior with levofloxacin 500 mg daily than with the other regimes (Kays MB, Denys GS. Diagn Microbiol Infect Dis. 2001;40:193-198).
Selection of Oxacillin Resistant S aureus by Fluoroquinolones
In vitro studies found that fluoroquinolones, especially ciprofloxacin (moxifloxacin, gatifloxacin, and levofloxacin were also studied) select out mec(A)-positive clones of S aureus from among a heteroresistant population (Venezia RA, et al. J Antimicrob Chemother. 2001; 48:375-381).
Flushing Fluoroquinolones
A Swiss study of urban wastewater effluents collected at treatment plants detected ciprofloxacin and norfloxacin in concentrations of 249 ng/L to 405 ng/mL in primary wastewater effluent and 45 to 102 ng/L in tertiary effluents (Golet EM, et al. Analytical Chem. 2001; 73:3632-3638).
Fluoroquinolones and Tendon Rupture
Although a population study found a 28% increase in nontraumatic tendon ruptures between 1991 and 1996, only 0.5% to 7% of the increase could be attributed to increased fluoroquinolone use (van der linden PD, et al. Pharm World Sci. 2001;23:89-92).
Colistin + Rifampin for Resistant Acinetobacter
Of 39 isolates of multidrug resistant Acinetobacter baumanii, 100% were inhibited by colistin (polymyxin E), synergy with rifampin was observed with some isolates (Giamarellos-Bourboulis EJ, et al. Diagn Microbiol Infect Dis. 2001;40:117-120).
THE IMMUNOCOMPROMISED HOST (NON-AIDS)
IL-2 and Common Variable Immunodeficiency
While common variable immunodeficiency is characterized by the presence of hypogammaglobulinemia and the lack of antibody response after antigen exposure, a variety of T cell defects, including reduced IL-2 production, have also been described in patients with this disorder. This paper reports that the administration of pegylated IL-2 for 12-18 months was associated with improved T cell proliferative responses and in vivo antibody production in response to a neoantigen (Cunningham-Rundles C, et al. Clin Immunol. 2001;100:181-190).
PCR Quantitation of EBV Genome
Semiquantitative PCR analysis found that EBV genome copy numbers per 105 PBMC ranged from 1000 to 40,000 in patients with infectious mononucleosis while it was < 100 in latently infected individuals and in asymptomatic renal transplant patients. Two bone marrow transplant patients had plasma levels of 16,000 and 50,000/mL as well as levels of 100,000 and 6.5 million copies 105 PBMC (Meerbach A, et al. J Med Virol. 2001;65:348-357).
BK and BMT
BK viruria is quantitatively related to the occurrence of hemorrhagic cystitis after bone marrow transplantation (Leung AYH, et al. Blood. 2001;98:1971-1978).
HIV/AIDS
Occult Antiretroviral Resistance in Treatment-Naïve Patients
While neither direct sequencing of HIV DNA from peripheral blood mononuclear cells (PBMC) nor HIV RNA from plasma isolates demonstrated the presence of drug resistance-associated mutations in the reverse transcriptase or protease genes, such mutations were detected by analysis of cloned HIV RNA and PBMC DNA at low frequencies in 4 of 5 treatment-naïve patients (Paolucci S, et al. J Med Virol. 2001;65:207-217).
RT, Protease Mutations, and Viral Replicative Fitness
Analysis of drug-resistant virus from 11 patients found that reduced replicative fitness was associated with the RT mutation M184I/V (11.6% decrease) and the PR mutations D30N (12.4% decrease) and M46I/L (21% decrease) (Devereux HL, et al. J Med Virol. 2001; 65:218-224).
HIV Protease Inhibitors—Direct Immunological Effects
Some recipients of HIV protease inhibitor therapy have persisting immunologic benefit despite virological failure. One reason for this discordant response may be a loss of viral fitness in the face of continued exposure protease inhibitor (PI) therapy (see above). Another proposed mechanism is a direct immunologic effect of PIs. Previous studies have reported that various PIs inhibit lymphocyte apoptosis, thus slowing the loss of lymphocytes. One group has now demonstrated that indinavir arrests lymphocyte cell cycling in G0/G1 phase in cells obtained from healthy volunteers as well as HIV-infected children. Such an effect may inhibit immune activation, thus preventing a state associated with disease progression (Chavan S, et al. Blood. 2001;98:383-389).
PI Concentration in Semen
Analysis of 45 paired serum and semen samples from 23 patients receiving antiretroviral therapy found that, while seminal plasma concentration of ritonavir and saquinavir were below their respective IC95s against wild type HIV-1, that of indinavir exceeded its IC95 (Taylor S, et al. J Antimicrob Chemother. 2001;48:351-354.)
HIV Protease Inhibitors Unstick Candida
HIV protease inhibitors, whose retroviral target is an aspartyl protease, have been reported to inhibit production of secreted aspartic proteases (saps), which are important virulence factors of Candida albicans, at least in part as a result of the role of saps in allowing adhesion to human epithelial cells. This study found that ritonavir, indinavir, and saquinavir inhibit adhesion of C albicans to epithelial cells (Bektic J, et al. FEMS Immunol Med Microbiol. 2001;31:65-71).
Indinavir and Bilirubin Conjugation
Indinavir causes unconjugated hyperbilirubinemia by competitively inhibiting bilirubin UDP glucuronosyltransferase activity, thus inhibiting bilirubin conjugation. The increase in bilirubin is greater in subjects with Gilbert’s syndrome—in which hepatic levels of this enzyme are already reduced (Zucker SD, et al. Proc Natl Acad Sci USA. 2001;98:12671-12676).
Gynecomastia and HAART
The incidence of gynecomastia in HIV-infected patients receiving HAART was 0.8 per 100 patient years; the prevalence among those who had received therapy from 2 years or more was 2.8%. Four patients with this condition were successfully treated with topical dihydrotestosterone gel (Piroth L, et al. Scand J Infect Dis. 2001;33:559-560; Beneniste O, et al. Clin Infect Dis. 2001;33:891-893).
Indinavir and Nephrolithiasis
Among 781 indinavir recipients with a median exposure to indinavir of 53 weeks, 7.3% developed renal complications; this represented an incidence of 6.7 per 100 person-years of indinavir exposure. Multivariate analysis found that treatment beyond 74 weeks was protective, while concomitant treatment with acyclovir increased the risk (Herman JS, et al. J Antimicrob Chemother. 2001;48:355-360).
Adefovir Nephrotoxicity and Renal Tubular Mitochondria
Adefovir, a nucleotide analog with activity against both HBV and HIV, was associated with significant nephrotoxicity in HIV infected patients and is being superseded by a similar drug, tenofovir. A study of renal biopsy material from a single patient suggests that the mechanism was reduction of mitochondrial DNA as a consequence of inhibition of mtDNA replication. The study is confounded by the fact that the patient was also receiving other antiretrovirals including stavudine and hydroxyurea (Tanji N, et al. Human Pathol. 2001;32:734-740).
DHEA in HIV Infection
In a randomized, double-blind, placebo-controlled trial involving 32 HIV-infected patients (mean CD4 count = 33 cells/mm3), administration of dehydroepiandrosterone sulphate (DHEA-S) was associated with a significant improvement in the Mental Health Distress dimension of the Medical Outcomes Study HIV Health Survey (MOS-HIV), but no change in CD4 count (Debuire B, et al. Clin Endocrinol. 2001;55:325-330).
Reversible ALS-Like Disorder in HIV Infection
Six HIV-infected patients (mean CD4 count = 86/mm3) developed distal motor weakness mimicking monomelic amyotrophy that rapidly progressed regionally or that developed a symmetric distribution involving more than one region. EMG was consistent with motor neuron disease. The neurological disease improved coincident with administration of antiretroviral therapy (Moulignier A, et al. Neurology. 2001;57:995-1001).
GEOGRAPHIC AND TRAVEL MEDICINE
DEET in Pregnancy
The safety of DEET use in the second and third trimesters of pregnancy was assessed in the context of a randomized trial involving 897 women. A median total dose of 214 g of DEET was applied with no evidence of adverse effects. Although DEET was detected in 8% of cord blood samples from a random subgroup, no adverse effects on the infant were found at 1 year follow-up (McGready R, et al. Am J Trop Med Hyg. 2001;65:285-289).
Chloroquine-Resistant Plasmodium vivax in Colombia
P vivax resistant to chloroquine are an emerging cause of infection in Asia and Oceania, with only rare case reports from other regions. This study reports that 3 of 27 (11%) patients with P vivax infection acquired in Colombia failed to respond to therapy with chloroquine (1500 mg base over 3 days). All responded to a second course of chloroquine given together with primaquine (Soto J, et al. Am J Trop Med Hyg. 2001;65:90-93).
QBC and Borreliosis
Relapsing fever, both the louse- and tick-borne varieties, are diagnosed by the relatively insensitive method of visual examination of Giemsa-stained blood smears. This study found that the use of fluorescence microscopy and acridine orange-coated quantitative buffy coat (QBC) tubes was an effective and sensitive diagnostic techniques. In fact, in vitro studies using B burgdorferi as a model found that the method could detect spirochetes at a concentration as low as 10 organisms/mm3 (Cobayae FC, et al. Am J Trop Med Hyg. 2001;65:164-165).
Strongyloidiasis on the Spanish Mediterranean Coast
One hundred fifty-two patients with strongyloidiasis were admitted to a single hospital in Valencia over an 8-year period. Sanchez and colleagues point out that this infestation is endemic on the Spanish Mediterranean coast, an area frequently visited by tourists (Sanchez PR, et al. QJM. 2001;94:357-363).
Liposomal Amphotericin B for Kala Azar
Nintey-one patients with Indian visceral leishmaniasis in India were randomized to receive 5 mg/kg liposomal amphotericin B to be given either as a single dose or as once daily infusions of 1 mg/kg with cure rates of, respectively, 92% and 93% (Sundar S, et al. BMJ. 2001;323:419-422).
Topical Cidofovir for Recalcitrant Orf
A renal transplant recipient receiving immunosuppressive therapy developed orf after contact with a freshly slaughtered sheep. The lesion progressed to massive size, failing to resolve despite a number of interventions. Complete and apparently permanent resolution of the lesion occurred in response to topical treatment with cidofovir (Geerinck K, et al. J Med Virol. 2001;64:543-549).
MISCELLANEOUS
Measles Virus in Asymptomatic Individuals
Measles virus genome was detected by PCR in asymptomatic infants previously exposed to wild measles virus and vaccine strain genome was detected in PBMCs of 10 (71.4%) of 14 infants sampled within 2 months of vaccination. Wild type measles genome was detected in PBMC of 6 (46.2%) of 13 individuals who had been naturally infected in the distant past. Measles genome was not detected in nasopharyngeal secretions (Eishubinger AM, et al. J Med Virol. 2001;65:395-401).
Immunologic Correlates of Protection from Anthrax
In rabbits who received Anthrax Vaccine Adsorbed, subsequent antibody levels to "Protective Antigen" at both 6 and 10 weeks were highly significant predictors of survival after an aerosol challenge with a lethal dose of Bacillus anthracis spores (Pitt ML, et al. Vaccine. 2001; 19:4768-4773).
Reduced Mortality in Childhood Meningococcal Disease
The overall mortality of 123 children admitted to the pediatric ICU at the Royal Liverpool Childrens Hospital between 1995 and 1998 was only 8.9% which may be compared with a predicted mortality of 24.9% and also lower than previously published studies. Similarly, in a review of 331 children seen at St. Mary’s Hospital in Norfolk, UK, from 1992-1997, the case fatality rate from fell from 23% to 2% over that time (Thorburn K, et al. Arch Dis Child. 2001;85:382-385; Booy R, et al. Arch Dis Child. 2001;85:386-390).
Doxycycline Therapy in Rheumatoid Arthritis?
Patients with erosive RA were randomized to receive IV doxycycline, po azithromycin, or placebo; no benefit was observed (St. Clair EW, et al. Arthritis Rheum. 2001; 44:1043-1047).
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