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Literature highlights: recent research in infectious disease drup resistance
Drug Resistance Updates 7 (2004) 311–315
Literature highlights
Recent research in infectious disease drug resistance
Guidelines developed for antimicrobial prophylaxis before surgery June 15, 2004 ST. LOUIS (MD Consult)—Guidelines regarding antimicrobial prophylaxis before surgery, developed by the Surgical Infection Prevention Guideline Writers Workgroup (SIPGWW), are presented in the June 15 Clinical Infectious Diseases. The guidelines were developed by authors from the major North American groups that have published similar guidelines and from several specialty societies. The positions they developed were circulated for comment, and their consensus conclusions are discussed. The SIPGWW guidelines recommend the first dose of antimicrobial prophylaxis be infused within 60 min before surgery. The exceptions are fluoroquinolones and vancomycin, which should begin 120 min before surgery to prevent drug-related adverse reactions. Antimicrobial prophylaxis should be discontinued within 24 h of wound closure to prevent the development of drug resistance. The guidelines discuss screening for -lactam allergy (medical history can usually suffice to identify allergic patients), which drugs to use in -lactam allergic patients (vancomycin and clindamycin), how to treat patients with methicillinresistant Staphylococcus aureus colonization (vancomycin), and the utility and recommended doses of other prophylactic antibiotics. They also provide specific antimicrobial recommendations for prophylaxis, depending on the type of surgery. Although these recommendations fill many of the gaps in prior recommendations, the authors emphasize the importance of continued surveillance in maintaining the efficacy of antimicrobial prophylaxis before surgery.
ST. LOUIS (MD Consult)—In some countries, almost 50% of Klebsiella pneumoniae isolates produce extendedspectrum beta-lactamases (ESBLs), which render the organism resistant to many antibiotics. Because of the lethal nature of K. pneumoniae, selecting an appropriate antibiotic is crucial to patient survival. So which drug to choose? Carbapenems should be the first choice for treating bacteremia due to ESBL-producing K. pneumoniae, according to the July 1 issue of Clinical Infectious Diseases. The recommendation, which was made by David Paterson and colleagues of the Veterans Administration Medical Center in Pittsburgh, Pennsylvania and other institutions, is based on a prospective, randomized study conducted in 12 hospitals in 7 countries. Of the 455 episodes of K. pneumoniae identified, 85 were due to ESBL-producing isolates. K. pneumoniae infection was associated with a high mortality rate: 7 of the 11 patients (63.6%) who were not treated with an effective antibiotic within 5 days of a positive blood culture died as compared with only 10 of 71 patients (14.1%) who were appropriately treated (odds ratio, 10.7). Among the 71 patients who were treated with an antibiotic effective against ESBL-producing K. pneumoniae, the 14-day mortality rate was significantly lower in those who received a carbapenem (primarily imipenem) within 5 days of a positive culture (2 of 42 patients [4.8%]) than in those who received other antibiotics (8 of 29 patients [27.6%]). Multivariate analyses confirmed that the use of a carbapenem within 5 days of a positive culture was independently and significantly associated with lower mortality (odds ratio, 0.09).
Which antibiotic is best for treating ESBL-producing Klebsiella pneumoniae?
Because the choice of antibiotic is so important in patients with bacteremia due to ESBL-producing K. pneumoniae, the authors suggest that carbapenem should be considered firstline therapy in these cases.
July 1, 2004
Clin. Infect. Dis. 2004;39:31–37.
Clin. Infect. Dis. 2004;38:1706–1715.
1368-7646/$ – see front matter doi:10.1016/j.drup.2004.10.001
312
Literature highlights / Drug Resistance Updates 7 (2004) 311–315
Value of sputum samples in diagnosing pneumococcal pneumonia depends on technique July 7, 2004 ST. LOUIS (MD Consult)—Reports of low sensitivity have prompted questions about the value of gram-stained sputum specimens and sputum cultures in the diagnosis of bacteremic pneumococcal pneumonia. However, a new study shows that these tools yield a correct diagnosis in >80% of cases if these techniques are properly used. Daniel M. Musher and colleagues of the Veterans Affairs Medical Center in Houston, Texas, discuss their findings in the July 15 Clinical Infectious Diseases. The authors examined the records of 105 patients with pneumonia in whom Streptococcus pneumoniae was isolated from blood. In each case, the authors noted when the sputum specimen was acquired and whether it was adequate for analysis. According to the medical records, Gram stains were positive in only 33 cases (31%), and sputum cultures were positive in only 46 cases (44%).
patients infected mostly with HIV-1 subtype B and receiving treatment. This assay combines RNA extraction with magnetic silica particles, amplification by nested reverse transcriptase PCR, and detection with high-density probe arrays designed to detect 204 antiretroviral resistance mutations simultaneously in Gag cleavage sites, protease, reverse transcriptase, integrase, and gp41. The nested reverse transcriptase PCR success rates at viral loads exceeding 1000 copies/ml were 98% for the 2.1-kb amplicon that covers the Gag cleavage sites and the protease and reverse transcriptase genes, 92% for the gp41 amplicon, and 100% for the integrase amplicon. The investigators analyzed 4465 relevant codons with the HIV-1 DNA chip genotyping assay and the classic sequence-based method. Key resistance mutations in protease and reverse transcriptase were identified correctly 95% and 92% of the time, respectively. This test should be a valuable alternative to the standard sequence-based system for HIV-1 drug resistance monitoring and a useful diagnostic tool for simultaneous multiple genetic analyses.
On closer examination, however, sputum specimens were never submitted in 31 cases, and, in another 16 cases, culture was not performed because the specimen was inadequate. If these cases are excluded, the sensitivity of Gram stain and culture was 57% and 79%, respectively. Moreover, when samples from patients who had been receiving antibiotics for at least 24 h were excluded, the sensitivity of Gram stain and culture improved to 63% and 86%, respectively.
J. Clin. Microbiol. 2004, July;42(7):2907–2912.
The authors suggest that sputum Gram stain and culture can improve the diagnosis of bacteremic pneumococcal pneumonia and reduce the risk of antimicrobial resistance associated with empiric therapy—if the specimens are promptly and properly collected and actually submitted for analysis.
Fifty-one clinical isolates and five clarithromycin-resistant mutants of Mycobacterium avium complex (MAC) were tested for their susceptibility to clarithromycin by microplate Alamar blue assay (MABA). The susceptibility results were compared with the results obtained by the BACTEC 460 method. All clinical isolates were susceptible, while all mutants were resistant to clarithromycin by BACTEC. Eighty-six percent of the clinical isolates were susceptible by MABA, and one of the resistant mutants was misclassified as susceptible by this method. The overall agreement between MABA and BACTEC was 86%, indicating the usefulness of MABA in drug susceptibility testing of MAC.
Clin. Infect. Dis. 2004;39:165–169. Detection of human immunodeficiency virus type 1 antiretroviral resistance mutations by high-density DNA probe arrays July 15, 2004 Gonzalez R, Masquelier B, Fleury H, Lacroix B, Troesch A, Vernet G, Telles JN Genotypic resistance testing has become an important tool in the clinical management of patients infected with human immunodeficiency virus type 1 (HIV-1). Standard sequencing methodology and hybridization-based technology are the two principal methods used for HIV-1 genotyping. Gonzalez and colleagues evaluated a new hybridizationbased HIV-1 genotypic assay in 99 clinical samples from
PMID: 15243037 [PubMed—in process] Evaluation of microplate Alamar blue assay for drug susceptibility testing of Mycobacterium avium complex isolates July 19, 2004 Vanitha JD, Paramasivan CN
Diagn. Microbiol. Infect. Dis. 2004, July;49(3):179–182. http://dx.doi.org/10.1016/j.diagmicrobio.2004.04.003 Which agents should we use for the treatment of multidrug-resistant Mycobacterium tuberculosis? Di Perri G, Bonora S The inappropriate treatment of drug-susceptible tuberculosis can lead to the selection and transmission of multidrugresistant tuberculosis (MDR-TB), indicating resistance
Literature highlights / Drug Resistance Updates 7 (2004) 311–315
313
to at least isoniazid and rifampicin. Residual first-line drugs, such as ethambutol, pyrazinamide and streptomycin, must then be appropriately combined with additional second-line drugs, guided by individual susceptibility patterns.
Ronald E. Polk and colleagues of the Surveillance and Control of Pathogens of Epidemiologic Importance (SCOPE)—MediMedia Information Technology (MMIT) Antimicrobial Monitoring Network discuss their findings in the August 15 Clinical Infectious Diseases.
Di Perri and Bonora (University of Turin, Italy) review the clinical pharmacology of these second-line antituberculous drugs. Fluoroquinolones represent the only substantial therapeutic advance in the last 20 years. Factors that may potentially affect the outcome of MDR-TB are: treatment adherence, prior exposure to antituberculous drugs, the number of drugs to which the infection is still susceptible and the time since the first diagnosis of tuberculosis. In making drug selection, the authors propose to follow a hierarchy based on the intrinsic activity against Mycobacterium tuberculosis and the clinical evidence of efficacy of the available active compounds.
The authors examined hospital fluoroquinolone use from 1999 (24 hospitals) through 2001 (35 hospitals). They also determined the number of fluoroquinolone prescriptions filled within a 10-mile radius of each participating hospital.
J. Antimicrob. Chemother. 2004, September;54(3):593–602.
In addition, the rates of fluoroquinolone-resistant P. aeruginosa also increased significantly, from 29% to 36%.
PMID: 15282233 [PubMed—in process] Molecular diagnosis of resistance to antimalarial drugs during epidemics and in war zones August 12, 2004 Djimde AA, Dolo A, Ouattara A, Diakite S, Plowe CV, Doumbo OK Plasmodium falciparum mutations pfcrt K76T and the dhfr/dhps “quintuple mutant” are molecular markers of resistance to chloroquine and sulfadoxine-pyrimethamine, respectively. During an epidemic of P. falciparum malaria in an area of political unrest in northern Mali, where standard efficacy studies have been impossible, Djimde and colleagues measured the prevalence of these markers in a cross-sectional survey. In 80% of cases of infection, pfcrt K76T was detected, but none of the cases carried the dhfr/dhps quintuple mutant. On the basis of these results, chloroquine was replaced by sulfadoxine-pyrimethamine in control efforts. This example illustrates how molecular markers for drug resistance can provide timely data that inform malaria-control policy during epidemics and other emergency situations. J. Infect. Dis. 2004, August 15;190(4):853–855. PMID: 15272415 [PubMed—in process] Study examines factors responsible for fluoroquinoloneresistant P. aeruginosa August 15, 2004 ST. LOUIS (MD Consult)—Fluoroquinolone-resistant Pseudomonas aeruginosa is increasing rapidly in the United States. A new study shows a hospital’s rate of fluoroquinolone-resistant P. aeruginosa can be predicted from the volume of fluoroquinolone use in the hospital and in the surrounding community.
During the study, use of fluoroquinolones increased significantly, from 137 to 163 defined daily doses per 1000 patient-days. The use of fluoroquinolones in the community also increased significantly, from 2.3 to 2.8 defined daily doses per 1000 inhabitant-days.
Multiple regression analysis indicated that the volumes of fluoroquinolone use in the hospital and in the community were each significant independent predictors of the drugresistant P. aeruginosa rate. These two variables predicted almost half of the variability in resistance rates between the hospitals (R2 = 0.43). When analyzed separately, levofloxacin use in both settings was a significant predictor of the development of resistant organisms. Ciprofloxacin use, however, was not predictive. Thus, levofloxacin appears to select for the development of drug-resistant P. aeruginosa more so than does ciprofloxacin. Regardless, if the current rates of fluoroquinolone use and antibiotic resistance continue, the entire drug class may lose its efficacy for fighting these pathogens. Clin. Infect. Dis. 2004;39:497–503. Model identifies nursing home residents at low risk of drug-resistant pneumonia August 15, 2004 ST. LOUIS (MD Consult)—Nursing-home-acquired pneumonia (NHAP) accounts for up to half of infections in nursing home residents. A model for predicting which residents are least likely to develop severe drug-resistant pneumonia is presented in the August 15 Clinical Infectious Diseases. Ali El Solh and colleagues of the University of Buffalo School of Medicine and Biomedical Sciences in New York studied 88 nursing home residents (58% men; mean age, about 82 years) with severe pneumonia. Of these, 17 were infected with at least 1 drug-resistant pathogen in the lower respiratory tract. Clinical and laboratory values from these patients were used in classification and regression tree analysis to create a model
314
Literature highlights / Drug Resistance Updates 7 (2004) 311–315
with 100% sensitivity for ruling out severe drug-resistant pneumonia. Two factors—the prior receipt of antibiotics and the activities of daily living (ADL) score—were identified and used in that order to create the classification tree. The ADL score assessed six major areas of activity on a 1to 3-point scale; the maximum score of 18 reflected total dependence. According to the classification tree, none of the 42 patients with no prior antibiotics and an ADL score of <12.5 developed severe drug-resistant pneumonia. The authors tested the model’s performance in another group of 47 nursing home residents. Again, the model correctly predicted the absence of drug-resistant pneumonia in all 25 patients with no prior antibiotics and an ADL score of <12.5. Specificity was 69.4%. Although confirmation in a large study is needed, this classification tree may provide a more rational basis for selecting the initial therapy in patients with NHAP. For example, a combination of nonpseudomonal third-generation cephalosporin or a beta-lactamase inhibitor/clavulanic acid with a macrolide would be appropriate for patients without prior antibiotic exposure and no major functional impairment. Clin. Infect. Dis. 2004;39:474–480. Incidence of extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) in 38 centres from 17 countries Bouchillon SK, Johnson BM, Hoban DJ, Johnson JL, et al. The study (PEARLS) prospectively monitored selected nosocomial pathogens from 38 centres in 13 European, three Middle Eastern countries and South Africa during 2001–2002. Extended spectrum beta-lactamase (ESBL) production rates among Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp. were 5.4%, 18.2% and 8.8%, respectively, for all study sites. The overall ESBL production rate for the combined Enterobacteriaceae was 10.5%, highest in Egypt, 38.5%, and Greece, 27.4%, and lowest in The Netherlands, 2.0%, and Germany, 2.6%. IEF, PCR and DNA sequencing determined 10.7% false positives among Enterobacter spp. when using NCCLS guidelines to screen for ESBL production.
Int. J. Antimicrob. Agents 2004;24:119–124. http://dx.doi.org/10.1016/j.ijantimicag.2004.01.010 Antimicrobial susceptibilities and analysis of genes related to penicillin or macrolide resistance in Streptococcus pneumoniae Hiramatsu K, Ohama M, Mijajima Y, Kishi K, et al. Hiramatsu and colleagues (Oita University, Japan) evaluated 177 strains of Streptococcus pneumoniae, derived from respiratory specimens between 1987 and 2001, for their antimicrobial susceptibilities and distribution of genes related to penicillin and macrolide resistance. Resistance rates tended to be higher for the 1996–2001 isolates than for the 1987–1995 isolates for all beta-lactams tested. For benzylpenicillin, the MIC(90) value of the isolates derived between 1996 and 2001 was 1.6 g/ml, while that of strains isolated between 1987 and 1990 was 0.05 g/ml. The number of strains susceptible to macrolides also decreased, but only two strains isolated in 1993 were resistant to quinolones (levofloxacin). When of genes relating to penicillin resistance were analysed using PCR with primers specific to susceptible alleles, more than 50% of strains from 1987 to 1990 and 1991 to 1995 revealed no mutations in the PBP 1a, 2x and 2b genes, but only 30.0% of strains derived between 1996 and 2001 showed no mutations in the PBP genes. Strains having mutations in all three PBP genes (1a, 2x and 2b) by the PCR method increased from 2.2% in the 1987–1990 derived strains to 27% in the 1996–2001 strains. Furthermore, 36% and 40% of the isolates from 1987 to 1990 and 1991 to 1995, respectively, possessed the mefA or ermB by PCR analysis, while 75% of isolates from 1996 to 2001 possessed mefA and/or ermB. These genetic changes may explain the increase in the number of penicillin and macrolide resistant strains. Int. J. Antimicrob. Agents 2004;24:125–129. http://dx.doi.org/10.1016/j.ijantimicag.2004.01.010 Peripheral neuropathy associated with prolonged use of linezolid Bressler AM, Zimmer SM, Gilmore JL, Somani J
The prevalence of nosocomial methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium was 32.4% and 8.7%, respectively.
Bressler and colleagues (Emory University Medical School, Atlanta, Georgia, USA) present a case of a woman who developed severe, painful peripheral neuropathy while receiving linezolid therapy for 6 months. Nerve conduction studies indicated a sensory-motor axonal neuropathy. At the time of death 1 month after discontinuing linezolid, the neuropathy had not resolved.
PEARLS provides baseline data against which prospective changes in resistant determinants and outcomes can be measured in this ongoing study.
A review of published material shows a growing body of evidence that long-term use of linezolid may be associated with severe peripheral and optic neuropathy. Twenty-one
Literature highlights / Drug Resistance Updates 7 (2004) 311–315
cases have been reported. In most cases, optic neuropathies resolved after stopping linezolid but peripheral neuropathies did not. The duration of therapy rather than indication for treatment seems to be the most important factor. The mechanism of toxicity is unknown but certain pharmacological properties of linezolid that may play a part are proposed.
315
This report highlights the importance of post-approval surveillance and reporting of serious adverse drug effects, and potential consequences of off-label use of pharmaceuticals. Lancet Infect. Dis. 2004, August;4(8):528–531. http://dx.doi.org/10.1016/S1473-3099(04)01109-0
Literature highlights
Recent research in infectious disease drug resistance
Guidelines developed for antimicrobial prophylaxis before surgery June 15, 2004 ST. LOUIS (MD Consult)—Guidelines regarding antimicrobial prophylaxis before surgery, developed by the Surgical Infection Prevention Guideline Writers Workgroup (SIPGWW), are presented in the June 15 Clinical Infectious Diseases. The guidelines were developed by authors from the major North American groups that have published similar guidelines and from several specialty societies. The positions they developed were circulated for comment, and their consensus conclusions are discussed. The SIPGWW guidelines recommend the first dose of antimicrobial prophylaxis be infused within 60 min before surgery. The exceptions are fluoroquinolones and vancomycin, which should begin 120 min before surgery to prevent drug-related adverse reactions. Antimicrobial prophylaxis should be discontinued within 24 h of wound closure to prevent the development of drug resistance. The guidelines discuss screening for -lactam allergy (medical history can usually suffice to identify allergic patients), which drugs to use in -lactam allergic patients (vancomycin and clindamycin), how to treat patients with methicillinresistant Staphylococcus aureus colonization (vancomycin), and the utility and recommended doses of other prophylactic antibiotics. They also provide specific antimicrobial recommendations for prophylaxis, depending on the type of surgery. Although these recommendations fill many of the gaps in prior recommendations, the authors emphasize the importance of continued surveillance in maintaining the efficacy of antimicrobial prophylaxis before surgery.
ST. LOUIS (MD Consult)—In some countries, almost 50% of Klebsiella pneumoniae isolates produce extendedspectrum beta-lactamases (ESBLs), which render the organism resistant to many antibiotics. Because of the lethal nature of K. pneumoniae, selecting an appropriate antibiotic is crucial to patient survival. So which drug to choose? Carbapenems should be the first choice for treating bacteremia due to ESBL-producing K. pneumoniae, according to the July 1 issue of Clinical Infectious Diseases. The recommendation, which was made by David Paterson and colleagues of the Veterans Administration Medical Center in Pittsburgh, Pennsylvania and other institutions, is based on a prospective, randomized study conducted in 12 hospitals in 7 countries. Of the 455 episodes of K. pneumoniae identified, 85 were due to ESBL-producing isolates. K. pneumoniae infection was associated with a high mortality rate: 7 of the 11 patients (63.6%) who were not treated with an effective antibiotic within 5 days of a positive blood culture died as compared with only 10 of 71 patients (14.1%) who were appropriately treated (odds ratio, 10.7). Among the 71 patients who were treated with an antibiotic effective against ESBL-producing K. pneumoniae, the 14-day mortality rate was significantly lower in those who received a carbapenem (primarily imipenem) within 5 days of a positive culture (2 of 42 patients [4.8%]) than in those who received other antibiotics (8 of 29 patients [27.6%]). Multivariate analyses confirmed that the use of a carbapenem within 5 days of a positive culture was independently and significantly associated with lower mortality (odds ratio, 0.09).
Which antibiotic is best for treating ESBL-producing Klebsiella pneumoniae?
Because the choice of antibiotic is so important in patients with bacteremia due to ESBL-producing K. pneumoniae, the authors suggest that carbapenem should be considered firstline therapy in these cases.
July 1, 2004
Clin. Infect. Dis. 2004;39:31–37.
Clin. Infect. Dis. 2004;38:1706–1715.
1368-7646/$ – see front matter doi:10.1016/j.drup.2004.10.001
312
Literature highlights / Drug Resistance Updates 7 (2004) 311–315
Value of sputum samples in diagnosing pneumococcal pneumonia depends on technique July 7, 2004 ST. LOUIS (MD Consult)—Reports of low sensitivity have prompted questions about the value of gram-stained sputum specimens and sputum cultures in the diagnosis of bacteremic pneumococcal pneumonia. However, a new study shows that these tools yield a correct diagnosis in >80% of cases if these techniques are properly used. Daniel M. Musher and colleagues of the Veterans Affairs Medical Center in Houston, Texas, discuss their findings in the July 15 Clinical Infectious Diseases. The authors examined the records of 105 patients with pneumonia in whom Streptococcus pneumoniae was isolated from blood. In each case, the authors noted when the sputum specimen was acquired and whether it was adequate for analysis. According to the medical records, Gram stains were positive in only 33 cases (31%), and sputum cultures were positive in only 46 cases (44%).
patients infected mostly with HIV-1 subtype B and receiving treatment. This assay combines RNA extraction with magnetic silica particles, amplification by nested reverse transcriptase PCR, and detection with high-density probe arrays designed to detect 204 antiretroviral resistance mutations simultaneously in Gag cleavage sites, protease, reverse transcriptase, integrase, and gp41. The nested reverse transcriptase PCR success rates at viral loads exceeding 1000 copies/ml were 98% for the 2.1-kb amplicon that covers the Gag cleavage sites and the protease and reverse transcriptase genes, 92% for the gp41 amplicon, and 100% for the integrase amplicon. The investigators analyzed 4465 relevant codons with the HIV-1 DNA chip genotyping assay and the classic sequence-based method. Key resistance mutations in protease and reverse transcriptase were identified correctly 95% and 92% of the time, respectively. This test should be a valuable alternative to the standard sequence-based system for HIV-1 drug resistance monitoring and a useful diagnostic tool for simultaneous multiple genetic analyses.
On closer examination, however, sputum specimens were never submitted in 31 cases, and, in another 16 cases, culture was not performed because the specimen was inadequate. If these cases are excluded, the sensitivity of Gram stain and culture was 57% and 79%, respectively. Moreover, when samples from patients who had been receiving antibiotics for at least 24 h were excluded, the sensitivity of Gram stain and culture improved to 63% and 86%, respectively.
J. Clin. Microbiol. 2004, July;42(7):2907–2912.
The authors suggest that sputum Gram stain and culture can improve the diagnosis of bacteremic pneumococcal pneumonia and reduce the risk of antimicrobial resistance associated with empiric therapy—if the specimens are promptly and properly collected and actually submitted for analysis.
Fifty-one clinical isolates and five clarithromycin-resistant mutants of Mycobacterium avium complex (MAC) were tested for their susceptibility to clarithromycin by microplate Alamar blue assay (MABA). The susceptibility results were compared with the results obtained by the BACTEC 460 method. All clinical isolates were susceptible, while all mutants were resistant to clarithromycin by BACTEC. Eighty-six percent of the clinical isolates were susceptible by MABA, and one of the resistant mutants was misclassified as susceptible by this method. The overall agreement between MABA and BACTEC was 86%, indicating the usefulness of MABA in drug susceptibility testing of MAC.
Clin. Infect. Dis. 2004;39:165–169. Detection of human immunodeficiency virus type 1 antiretroviral resistance mutations by high-density DNA probe arrays July 15, 2004 Gonzalez R, Masquelier B, Fleury H, Lacroix B, Troesch A, Vernet G, Telles JN Genotypic resistance testing has become an important tool in the clinical management of patients infected with human immunodeficiency virus type 1 (HIV-1). Standard sequencing methodology and hybridization-based technology are the two principal methods used for HIV-1 genotyping. Gonzalez and colleagues evaluated a new hybridizationbased HIV-1 genotypic assay in 99 clinical samples from
PMID: 15243037 [PubMed—in process] Evaluation of microplate Alamar blue assay for drug susceptibility testing of Mycobacterium avium complex isolates July 19, 2004 Vanitha JD, Paramasivan CN
Diagn. Microbiol. Infect. Dis. 2004, July;49(3):179–182. http://dx.doi.org/10.1016/j.diagmicrobio.2004.04.003 Which agents should we use for the treatment of multidrug-resistant Mycobacterium tuberculosis? Di Perri G, Bonora S The inappropriate treatment of drug-susceptible tuberculosis can lead to the selection and transmission of multidrugresistant tuberculosis (MDR-TB), indicating resistance
Literature highlights / Drug Resistance Updates 7 (2004) 311–315
313
to at least isoniazid and rifampicin. Residual first-line drugs, such as ethambutol, pyrazinamide and streptomycin, must then be appropriately combined with additional second-line drugs, guided by individual susceptibility patterns.
Ronald E. Polk and colleagues of the Surveillance and Control of Pathogens of Epidemiologic Importance (SCOPE)—MediMedia Information Technology (MMIT) Antimicrobial Monitoring Network discuss their findings in the August 15 Clinical Infectious Diseases.
Di Perri and Bonora (University of Turin, Italy) review the clinical pharmacology of these second-line antituberculous drugs. Fluoroquinolones represent the only substantial therapeutic advance in the last 20 years. Factors that may potentially affect the outcome of MDR-TB are: treatment adherence, prior exposure to antituberculous drugs, the number of drugs to which the infection is still susceptible and the time since the first diagnosis of tuberculosis. In making drug selection, the authors propose to follow a hierarchy based on the intrinsic activity against Mycobacterium tuberculosis and the clinical evidence of efficacy of the available active compounds.
The authors examined hospital fluoroquinolone use from 1999 (24 hospitals) through 2001 (35 hospitals). They also determined the number of fluoroquinolone prescriptions filled within a 10-mile radius of each participating hospital.
J. Antimicrob. Chemother. 2004, September;54(3):593–602.
In addition, the rates of fluoroquinolone-resistant P. aeruginosa also increased significantly, from 29% to 36%.
PMID: 15282233 [PubMed—in process] Molecular diagnosis of resistance to antimalarial drugs during epidemics and in war zones August 12, 2004 Djimde AA, Dolo A, Ouattara A, Diakite S, Plowe CV, Doumbo OK Plasmodium falciparum mutations pfcrt K76T and the dhfr/dhps “quintuple mutant” are molecular markers of resistance to chloroquine and sulfadoxine-pyrimethamine, respectively. During an epidemic of P. falciparum malaria in an area of political unrest in northern Mali, where standard efficacy studies have been impossible, Djimde and colleagues measured the prevalence of these markers in a cross-sectional survey. In 80% of cases of infection, pfcrt K76T was detected, but none of the cases carried the dhfr/dhps quintuple mutant. On the basis of these results, chloroquine was replaced by sulfadoxine-pyrimethamine in control efforts. This example illustrates how molecular markers for drug resistance can provide timely data that inform malaria-control policy during epidemics and other emergency situations. J. Infect. Dis. 2004, August 15;190(4):853–855. PMID: 15272415 [PubMed—in process] Study examines factors responsible for fluoroquinoloneresistant P. aeruginosa August 15, 2004 ST. LOUIS (MD Consult)—Fluoroquinolone-resistant Pseudomonas aeruginosa is increasing rapidly in the United States. A new study shows a hospital’s rate of fluoroquinolone-resistant P. aeruginosa can be predicted from the volume of fluoroquinolone use in the hospital and in the surrounding community.
During the study, use of fluoroquinolones increased significantly, from 137 to 163 defined daily doses per 1000 patient-days. The use of fluoroquinolones in the community also increased significantly, from 2.3 to 2.8 defined daily doses per 1000 inhabitant-days.
Multiple regression analysis indicated that the volumes of fluoroquinolone use in the hospital and in the community were each significant independent predictors of the drugresistant P. aeruginosa rate. These two variables predicted almost half of the variability in resistance rates between the hospitals (R2 = 0.43). When analyzed separately, levofloxacin use in both settings was a significant predictor of the development of resistant organisms. Ciprofloxacin use, however, was not predictive. Thus, levofloxacin appears to select for the development of drug-resistant P. aeruginosa more so than does ciprofloxacin. Regardless, if the current rates of fluoroquinolone use and antibiotic resistance continue, the entire drug class may lose its efficacy for fighting these pathogens. Clin. Infect. Dis. 2004;39:497–503. Model identifies nursing home residents at low risk of drug-resistant pneumonia August 15, 2004 ST. LOUIS (MD Consult)—Nursing-home-acquired pneumonia (NHAP) accounts for up to half of infections in nursing home residents. A model for predicting which residents are least likely to develop severe drug-resistant pneumonia is presented in the August 15 Clinical Infectious Diseases. Ali El Solh and colleagues of the University of Buffalo School of Medicine and Biomedical Sciences in New York studied 88 nursing home residents (58% men; mean age, about 82 years) with severe pneumonia. Of these, 17 were infected with at least 1 drug-resistant pathogen in the lower respiratory tract. Clinical and laboratory values from these patients were used in classification and regression tree analysis to create a model
314
Literature highlights / Drug Resistance Updates 7 (2004) 311–315
with 100% sensitivity for ruling out severe drug-resistant pneumonia. Two factors—the prior receipt of antibiotics and the activities of daily living (ADL) score—were identified and used in that order to create the classification tree. The ADL score assessed six major areas of activity on a 1to 3-point scale; the maximum score of 18 reflected total dependence. According to the classification tree, none of the 42 patients with no prior antibiotics and an ADL score of <12.5 developed severe drug-resistant pneumonia. The authors tested the model’s performance in another group of 47 nursing home residents. Again, the model correctly predicted the absence of drug-resistant pneumonia in all 25 patients with no prior antibiotics and an ADL score of <12.5. Specificity was 69.4%. Although confirmation in a large study is needed, this classification tree may provide a more rational basis for selecting the initial therapy in patients with NHAP. For example, a combination of nonpseudomonal third-generation cephalosporin or a beta-lactamase inhibitor/clavulanic acid with a macrolide would be appropriate for patients without prior antibiotic exposure and no major functional impairment. Clin. Infect. Dis. 2004;39:474–480. Incidence of extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) in 38 centres from 17 countries Bouchillon SK, Johnson BM, Hoban DJ, Johnson JL, et al. The study (PEARLS) prospectively monitored selected nosocomial pathogens from 38 centres in 13 European, three Middle Eastern countries and South Africa during 2001–2002. Extended spectrum beta-lactamase (ESBL) production rates among Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp. were 5.4%, 18.2% and 8.8%, respectively, for all study sites. The overall ESBL production rate for the combined Enterobacteriaceae was 10.5%, highest in Egypt, 38.5%, and Greece, 27.4%, and lowest in The Netherlands, 2.0%, and Germany, 2.6%. IEF, PCR and DNA sequencing determined 10.7% false positives among Enterobacter spp. when using NCCLS guidelines to screen for ESBL production.
Int. J. Antimicrob. Agents 2004;24:119–124. http://dx.doi.org/10.1016/j.ijantimicag.2004.01.010 Antimicrobial susceptibilities and analysis of genes related to penicillin or macrolide resistance in Streptococcus pneumoniae Hiramatsu K, Ohama M, Mijajima Y, Kishi K, et al. Hiramatsu and colleagues (Oita University, Japan) evaluated 177 strains of Streptococcus pneumoniae, derived from respiratory specimens between 1987 and 2001, for their antimicrobial susceptibilities and distribution of genes related to penicillin and macrolide resistance. Resistance rates tended to be higher for the 1996–2001 isolates than for the 1987–1995 isolates for all beta-lactams tested. For benzylpenicillin, the MIC(90) value of the isolates derived between 1996 and 2001 was 1.6 g/ml, while that of strains isolated between 1987 and 1990 was 0.05 g/ml. The number of strains susceptible to macrolides also decreased, but only two strains isolated in 1993 were resistant to quinolones (levofloxacin). When of genes relating to penicillin resistance were analysed using PCR with primers specific to susceptible alleles, more than 50% of strains from 1987 to 1990 and 1991 to 1995 revealed no mutations in the PBP 1a, 2x and 2b genes, but only 30.0% of strains derived between 1996 and 2001 showed no mutations in the PBP genes. Strains having mutations in all three PBP genes (1a, 2x and 2b) by the PCR method increased from 2.2% in the 1987–1990 derived strains to 27% in the 1996–2001 strains. Furthermore, 36% and 40% of the isolates from 1987 to 1990 and 1991 to 1995, respectively, possessed the mefA or ermB by PCR analysis, while 75% of isolates from 1996 to 2001 possessed mefA and/or ermB. These genetic changes may explain the increase in the number of penicillin and macrolide resistant strains. Int. J. Antimicrob. Agents 2004;24:125–129. http://dx.doi.org/10.1016/j.ijantimicag.2004.01.010 Peripheral neuropathy associated with prolonged use of linezolid Bressler AM, Zimmer SM, Gilmore JL, Somani J
The prevalence of nosocomial methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium was 32.4% and 8.7%, respectively.
Bressler and colleagues (Emory University Medical School, Atlanta, Georgia, USA) present a case of a woman who developed severe, painful peripheral neuropathy while receiving linezolid therapy for 6 months. Nerve conduction studies indicated a sensory-motor axonal neuropathy. At the time of death 1 month after discontinuing linezolid, the neuropathy had not resolved.
PEARLS provides baseline data against which prospective changes in resistant determinants and outcomes can be measured in this ongoing study.
A review of published material shows a growing body of evidence that long-term use of linezolid may be associated with severe peripheral and optic neuropathy. Twenty-one
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cases have been reported. In most cases, optic neuropathies resolved after stopping linezolid but peripheral neuropathies did not. The duration of therapy rather than indication for treatment seems to be the most important factor. The mechanism of toxicity is unknown but certain pharmacological properties of linezolid that may play a part are proposed.
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This report highlights the importance of post-approval surveillance and reporting of serious adverse drug effects, and potential consequences of off-label use of pharmaceuticals. Lancet Infect. Dis. 2004, August;4(8):528–531. http://dx.doi.org/10.1016/S1473-3099(04)01109-0