- Volume 70, Issue 12, 2021
Volume 70, Issue 12, 2021
- JMM Profiles
-
-
-
JMM Profile: Carbapenems: a broad-spectrum antibiotic
More LessCarbapenems are potent members of the β-lactam family that inhibit bacterial cell-wall biosynthesis inhibitors . They are highly effective against Gram-negative and Gram-positive drug-resistant infections . As such, carbapenems are typically reserved as an antibiotic of last resort. The WHO lists meropenem as an essential medicine. Nausea and vomiting are reported in ≤20% of carbapenem recipients, with 1.5% suffering seizures. Enzymatic hydrolysis of the β-lactam ring is the main driver of clinical resistance. These enzymes can be classified as Class A, B and D. Classes A and D are serine β-lactamases, whereas Class B rely on metal-mediated hydrolysis, typically through zinc.
-
-
- Antimicrobial Resistance
-
-
-
Prevalence of genotypic antimicrobial resistance in clinical Shiga toxin-producing Escherichia coli in Norway, 2018 to 2020
Introduction. Shiga toxin-producing Escherichia coli (STEC) can cause severe to fatal disease in humans. Antimicrobial treatment is sometimes necessary, but contraindicated due to undesirable clinical outcome. However, recent studies have shown promising outcomes following antimicrobial treatment. Before the establishment of a possible antimicrobial treatment strategy for STEC infections, the prevalence of antimicrobial resistance in STEC needs to be determined.
Gap Statement. The resistance status of Norwegian clinical STEC is not known and should be assessed.
Aim. We aim to characterize genotypic antimicrobial resistance determinants in clinical STEC in Norway, and determine the prevalence of genotypic resistance in order to inform possible antimicrobial treatment options for STEC infections.
Methodology. We included all clinical STEC submitted to the Norwegian Reference Laboratory from March 2018 to April 2020. All samples were whole-genome sequenced and screened for genotypic antimicrobial resistance,virulence determinants and plasmid incompatibility groups. We performed phylogenetic clustering of STEC by core-genome multi-locus sequence typing, and statistical association analyses between isolate characteristics and genotypic resistance.
Results. A total of 459 STEC were analysed. For 385 (83.9 %) STEC we did not identify any antimicrobial resistance determinants. Seventy-four STEC (16.1 %) harboured antimicrobial resistance determinants against one or more antimicrobial classes. The most frequent genotypic resistance was identified against aminoglycosides (10.5 %). Thirty-nine STEC (8.5 %) had a multi-drug resistance (MDR) genotype. Genotypic resistance was more prevalent in non-O157 than O157 STEC (P=0.02). A positive association was seen between genotypic resistance and the low-virulent STEC O117:H7 phylogenetic cluster (no. 14) (P<0.001). Genotypic resistance was not significantly associated to high-virulent STEC. STEC O146:H28 and isolates harbouring the plasmid replicon type IncQ1 were positively associated with MDR.
Conclusion. The overall prevalence of genotypic resistance in clinical STEC in Norway is low (16.1 %). Genotypic resistance is more prevalent in non-O157 strains compared to O157 strains, and not significantly associated to high-virulent STEC. Resistance to antimicrobials suggested for treatment, especially azithromycin is low and may present an empiric treatment alternative for severe STEC infections.
-
-
-
-
Antifungal susceptibility profile of invasive Candida glabrata isolates (2009–2020) from a tertiary care hospital laboratory in Pakistan
More LessIntroduction. Invasive infections with Candida glabrata are a global concern due to poor clinical outcomes and propensity to acquire resistance to antifungal agents.
Hypothesis/Gap Statement. Monitoring emerging resistance and trends in Candida glabrata, an important agent of candidemia in Pakistan, is critical for patient management; data that is missing from Pakistan.
Aim. Thus, this study evaluated antifungal resistance and MICs) distribution in invasive C. glabrata isolates from Pakistan.
Methods. This cross-sectional and retrospective study was conducted from January 2009 to March 2020 at a clinical laboratory in Pakistan that has a nation-wide network. Antifungal susceptibility data of 277 candidemia, deep organ and soft tissue (invasive) C. glabrata sensu lato isolates against fluconazole, itraconazole, voriconazole, posaconazole, anidulafungin, micafungin, caspofungin and amphotericin B was retrieved. Susceptibility testing was performed using colorimetric broth microdilution and interpreted using CLSI criteria. Demographics, clinical history and outcome were studied. Chi-square test was used to demonstrate association between antifungal resistance and clinical characteristics of the patients.
Results. We identified 277 patients with invasive C. glabrata infection. Of which 48 (18.4%) isolates were resistant to fluconazole (MIC ≥64 mg l−1), one isolate each was resistant to amphotericin (MIC=2 mg l−1), anidulafungin (MIC=1 mg l−1) and micafungin (MIC=0.5 mg l−1). MIC90 for fluconazole was 64 mg l−1 and other triazoles 2 mg l−1, caspofungin 0.12 mg l−1, anidulafungin 0.06 mg l−1, micafungin 0.03 mg l−1 and amphotericin 0.5 mg l−1. Fluconazole MIC ≥64 mg l−1, caspofungin MIC >0.06 mg l−1 and amphotericin MIC >0.25 mg l−1 (above MIC50) were significantly associated with patient being alive at the time of reporting, no use of healthcare devices, nor infection with other fungi. Fluconazole resistance was significantly associated with prior antifungal use by the patient.
Conclusion. Surveillance data of antifungal resistance among common Candida species should be monitored closely for identification of resistant strains.
-
-
-
National trends in hospital, long-term care and outpatient Acinetobacter baumannii resistance rates
More LessIntroduction. Acinetobacter baumannii is a top-priority pathogen of the World Health Organization (WHO) and the Centers for Disease Control (CDC) due to antibiotic resistance.
Gap Statement. Trends in A. baumannii resistance rates that include community isolates are unknown.
Aim. Identify trends in A. baumannii resistance rates across the Veterans Affairs (VA) Healthcare System, including isolates from patients treated in hospitals, long-term care facilities and outpatient clinics nationally.
Methodology. We included A. baumannii clinical cultures collected from VA patients from 2010 to 2018. Cultures were categorized by location: VA medical centers (VAMCs), long-term care (LTC) units [community living centers (CLCs)], or outpatient. We assessed carbapenem resistance, multidrug resistance (MDR) and extensive drug resistance (XDR). Time trends were assessed with Joinpoint regression.
Results. We identified 19 376 A . baumannii cultures (53% VAMCs, 4% CLCs, 43% outpatient). Respiratory cultures were the most common source of carbapenem-resistant (43 %), multidrug-resistant (49 %) and extensively drug-resistant (21 %) isolates. Over the study period, the number of A. baumannii cultures decreased significantly in VAMCs (11.9% per year). In 2018, carbapenem resistance was seen in 28% of VAMC isolates and 36% of CLC isolates, but only 6% of outpatient isolates, while MDR was found in 31% of VAMC isolates and 36% of CLC isolates, but only 8 % of outpatient isolates. Carbapenem-resistant, multidrug-resistant and extensively drug-resistant A. baumannii isolates decreased significantly in VAMCs and outpatient clinics over time (VAMCs: by 4.9, 7.2 and 6.9%; outpatient: by 11.3, 10.5 and 10.2% per year). Resistant phenotypes remained stable in CLCs.
Conclusion. In the VA nationally, the prevalence of A. baumannii is decreasing, as is resistance. Carbapenem-resistant and multidrug-resistant A. baumannii remain common in VAMCs and CLCs. The focus of infection control and antimicrobial stewardship efforts to prevent transmission of resistant A. baumannii should be in hospital and LTC settings.
-
- Clinical Microbiology
-
-
-
Comparing hospital-resource utilization by an enhanced pneumonia surveillance programme for COVID-19 with pre-pandemic pneumonia admissions – a Singaporean hospital’s experience
More LessIntroduction. During the early days of coronavirus disease 2019 (COVID-19) in Singapore, Tan Tock Seng Hospital implemented an enhanced pneumonia surveillance (EPS) programme enrolling all patients who were admitted from the Emergency Department (ED) with a diagnosis of pneumonia but not meeting the prevalent COVID-19 suspect case definition.
Hypothesis/Gap Statement. There is a paucity of data supporting the implementation of such a programme.
Aims. To compare and contrast our hospital-resource utilization of an EPS programme for COVID-19 infection detection with a suitable comparison group.
Methodology. We enrolled all patients admitted under the EPS programme from TTSH’s ED from 7 February 2020 (date of EPS implementation) to 20 March 2020 (date of study ethics application) inclusive. We designated a comparison cohort over a similar duration the preceding year. Relevant demographic and clinical data were extracted from the electronic medical records.
Results. There was a 3.2 times higher incidence of patients with an admitting diagnosis of pneumonia from the ED in the EPS cohort compared to the comparison cohort (P<0.001). However, there was no significant difference in the median length of stay of 7 days (P=0.160). Within the EPS cohort, stroke and fluid overload occur more frequently as alternative primary diagnoses.
Conclusions. Our study successfully evaluated our hospital-resource utilization demanded by our EPS programme in relation to an appropriate comparison group. This helps to inform strategic use of hospital resources to meet the needs of both COVID-19 related services and essential ‘peace-time’ healthcare services concurrently.
-
-
-
-
Development of a nucleic acid chromatography assay for the detection of commonly isolated rapidly growing mycobacteria
Introduction. Non-tuberculosis mycobacterium infections are increasing worldwide, including those caused by rapidly growing mycobacteria (RGM).
Gap Statement. The identification of the aetiological agent in the context of infections is essential for the adoption of an adequate therapeutic approach. However, the methods for the rapid distinction of different RGM species are less than optimal.
Aim. To develop a nucleic acid chromatography kit to identify clinically common RGM.
Methodology. We tried to develop a nucleic acid chromatography kit designed to detect four RGM species (including three subspecies) i.e. Mycobacterium abscessus subsp. abscessus , Mycobacterium abscessus subsp. bolletii (detected as M. abscessus/bolletii) Mycobacterium abscessus subsp. massiliense , Mycobacterium fortuitum , Mycobacterium chelonae and Mycobacterium peregrinum . The amplified target genes for each species/subspecies using multiplex PCR were analysed using a nucleic acid chromatography assay.
Results. Among the 159 mycobacterial type strains and 70 RGM clinical isolates tested, the developed assay correctly identified all relevant RGM without any cross-reactivity or false-negatives. The limits of detection for each species were approximately 0.2 pg µl-1.
Conclusion. The rapid and simple nucleic acid chromatography method developed here, which does not involve heat denaturation, may contribute to the rapid identification and treatment of RGM infections.
-
-
-
Treating autism spectrum disorder by intervening with gut microbiota
More LessAutism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders with a high prevalence in childhood. The gut microbiota can affect human cognition and moods and has a strong correlation with ASD. Microbiota transplantation, including faecal microbiota transplantation (FMT), probiotics, breastfeeding, formula feeding, gluten-free and casein-free (GFCF) diet and ketogenic diet therapy, may provide satisfying effects for ASD and its related various symptoms. For instance, FMT can improve the core symptoms of ASD and gastrointestinal symptoms. Probiotics, breastfeeding and formula feeding, and GFCF diet can improve gastrointestinal symptoms. The core symptom score still needs to be confirmed by large-scale clinical randomized controlled studies. It is recommended to use a ketogenic diet to treat patients with epilepsy in ASD. At present, the unresolved problems include which of gut the microbiota are beneficial, which of the microorganisms are harmful, how to safely and effectively implant beneficial bacteria into the human body, and how to extract and eliminate harmful microorganisms before transplantation. In future studies, large sample and randomized controlled clinical studies are needed to confirm the mechanism of intestinal microorganisms in the treatment of ASD and the method of microbial transplantation.
-
-
-
Epidemiology and genomic analysis of Shiga toxin-producing Escherichia coli clonal complex 165 in the UK
Introduction. Shiga toxin-producing Escherichia coli (STEC) is a zoonotic, foodborne gastrointestinal pathogen that has the potential to cause severe clinical outcomes, including haemolytic uraemic syndrome (HUS). STEC-HUS is the leading cause of renal failure in children and can be fatal. Over the last decade, STEC clonal complex 165 (CC165) has emerged as a cause of STEC-HUS.
Gap Statement. There is a need to understand the pathogenicity and prevalence of this emerging STEC clonal complex in the UK, to facilitate early diagnosis, improve clinical management, and prevent and control outbreaks.
Aim. The aim of this study was to characterize CC165 through identification of virulence factors (VFs) and antimicrobial resistance (AMR) determinants in the genome and to integrate the genome data with the available epidemiological data to better understand the incidence and pathogenicity of this clonal complex in the UK.
Methodology. All isolates belonging to CC165 in the archives at the UK public health agencies were sequenced and serotyped, and the virulence gene and AMR profiles were derived from the genome using PHE bioinformatics pipelines and the Centre for Genomic Epidemiology virulence database.
Results. There were 48 CC165 isolates, of which 43 were STEC, four were enteropathogenic E. coli (EPEC) and one E. coli . STEC serotypes were predominately O80:H2 (n=28), and other serotypes included O45:H2 (n=9), O55:H9 (n=4), O132:H2 (n=1) and O180:H2 (n=1). All but one STEC isolate had Shiga toxin (stx) subtype stx2a or stx2d and 47/48 isolates had the eae gene encoding intimin involved in the intimate attachment of the bacteria to the human gut mucosa. We detected extra-intestinal virulence genes including those associated with iron acquisition (iro) and serum resistance (iss), indicating that this pathogen has the potential to translocate to extra-intestinal sites. Unlike other STEC clonal complexes, a high proportion of isolates (93%, 40/43) were multidrug-resistant, including resistance to aminoglycosides, beta-lactams, chloramphenicol, sulphonamides, tetracyclines and trimethoprim.
Conclusion. The clinical significance of this clonal complex should not be underestimated. Exhibiting high levels of AMR and a combination of STEC and extra-intestinal pathogenic E. coli (ExPEC) virulence profiles, this clonal complex is an emerging threat to public health.
-
- Disease, Diagnosis and Diagnostics
-
-
-
A pentaplex real-time PCR assay for rapid identification of major beta-lactamase genes KPC, NDM, CTX, CMY, and OXA-48 directly from bacteria in blood
Introduction. Antibiotic resistance, particularly in cases of sepsis, has emerged as a growing global public health concern and economic burden. Current methods of blood culture and antimicrobial susceptibility testing of agents involved in sepsis can take as long as 3–5 days. It is vital to rapidly identify which antimicrobials can be used to effectively treat sepsis cases on an individual basis. Here, we present a pentaplex, real-time PCR-based assay that can quickly identify the most common beta-lactamase genes ( Klebsiella pneumoniae carbapenemase (KPC); New Delhi metallo-beta-lactamase (NDM); cefotaximase-Munich (CTX-M); cephamycin AmpC beta-lactamases (CMY); and Oxacillinase-48 (OXA-48)) from pathogens derived directly from the blood of patients presenting with bacterial septicemia.
Aim. To develop an assay which can rapidly identify the most common beta-lactamase genes in Carbapenem-resistant Enterobacteriaceae bacteria (CREs) from the United States.
Hypothesis/Gap Statement. Septicemia caused by carbapenem-resistant bacteria has a death rate of 40–60 %. Rapid diagnosis of antibiotic susceptibility directly from bacteria in blood by identification of beta-lactamase genes will greatly improve survival rates. In this work, we develop an assay capable of concurrently identifying the five most common beta-lactamase and carbapenemase genes.
Methodology. Primers and probes were created which can identify all subtypes of Klebsiella pneumoniae carbapenemase (KPC); New Delhi metallo-beta-lactamase (NDM); cefotaximase-Munich (CTX); cephamycin AmpC beta-lactamase (CMY); and oxacillinase-48 (OXA-48). The assay was validated using 13 isolates containing various PCR targets from the Centre for Disease Control Antimicrobial Resistance Isolate Bank Enterobacterales Carbapenemase Diversity Panel. Blood obtained from volunteers was spiked with CREs and bacteria were separated, lysed, and subjected to analysis via the pentaplex assay.
Results. This pentaplex assay successfully identified beta-lactamase genes derived from bacteria separated from blood at concentrations of 4–8 c.f.u. ml−1.
Conclusion. This assay will improve patient outcomes by supplying physicians with critical drug resistance information within 2 h of septicemia onset, allowing them to prescribe effective antimicrobials corresponding to the resistance gene(s) present in the pathogen. In addition, information supplied by this assay will lessen the inappropriate use of broad-spectrum antimicrobials and prevent the evolution of further antibiotic resistance.
-
-
-
-
Use of Sysmex UF-5000 flow cytometry in rapid diagnosis of urinary tract infection and the importance of validating carryover rates against bacterial count cut-off
Introduction. Urinary tract infections are common bacterial infections worldwide. Urine culture is the gold standard method to identify and quantify the presence or absence of bacteria in urine. Flow cytometry, which can differentiate and quantify multiple particles (including bacteria) in the urine, presents an alternative method for rapid screening to rule out bacteriuria.
Hypothesis. Adding flow cytometry to identify urine samples without bacteriuria could substantially reduce the number of urine samples that need to be cultured as well as the response time for negative results. However, the level of instrument rinsing between samples could affect sample-to-sample carryover rate, a concept given little attention in previous studies.
Aim. We aimed to evaluate urine flow cytometry as a rapid screening method to identify urine samples without significant bacterial growth, including analyses of cross-contamination and sample-to-sample carryover rate.
Methodology. We analysed 3919 urine samples by quantitative urine culture and flow cytometry screening (Sysmex UF-5000). Receiver operator characteristic (ROC) curve analyses were used to test method agreement to identify: (a) positive vs. negative culture and (b) mixed vs. pure culture. In addition, we performed carryover and cross-contamination studies.
Results. ROC curve analyses identified bacterial count (BACT ml−1) and leucocyte count (WBC µl−1) as possible predictors of bacterial growth in the total material and subpopulations, except pregnant women (n=451). This subgroup was excluded from further analyses, leaving a final 3468 urine samples. Area under the ROC curve was 0.94 (95 % CI 0.93–0.95) and 0.81 (95 % CI 0.79–0.82) for bacterial and leucocyte count, respectively. A bacterial count cut-off of 30 BACT ml−1 resulted in 95.2 % sensitivity and 91.2 % negative predictive value, resulting in approximately 30 % of urine samples that could be reported as negative without culture. Use of high-level rinse modes was necessary to ensure carryover rates <0.05 %.
Conclusion. Flow cytometry is a suitable and rapid method to rule out urine samples without significant bacterial growth. Rinses between samples should be adjusted, depending on the cut-off used, to prevent sample-to-sample carryover, whereas cross-contamination can be eliminated by the use of separate urine aliquots for flow cytometry analysis and urine culturing respectively.
-
- Medical Mycology
-
-
-
Additional C-type lectin receptors mediate interactions with Pneumocystis organisms and major surface glycoprotein
More LessIntroduction. Pathogen-associated molecular patterns’ (PAMPs) are microbial signatures that are recognized by host myeloid C-type lectin receptors (CLRs). These CLRs interact with micro-organisms via their carbohydrate recognition domains (CRDs) and engage signalling pathways within the cell resulting in pro-inflammatory and microbicidal responses.
Gap statement. In this article, we extend our laboratory study of additional CLRs that recognize fungal ligands against Pneumocystis murina and Pneumocystis carinii and their purified major surface glycoproteins (Msgs).
Aim. To study the potential of newly synthesized hFc-CLR fusions on binding to Pneumocystis and its Msg.
Methods. A library of new synthesized hFc-CLR fusions was screened against Pneumocystis murina and Pneumocystis carinii organisms and their purified major surface glycoproteins (Msgs) found on the respective fungi via modified ELISA. Immunofluorescence assay (IFA) was implemented and quantified to verify results. mRNA expression analysis by quantitative PCR (q-PCR) was employed to detect respective CLRs found to bind fungal organisms in the ELISA and determine their expression levels in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model.
Results. We detected a number of the CLR hFc-fusions displayed significant binding with P. murina and P. carinii organisms, and similarly to their respective Msgs. Significant organism and Msg binding was observed for CLR members C-type lectin domain family 12 member A (CLEC12A), Langerin, macrophage galactose-type lectin-1 (MGL-1), and specific intracellular adhesion molecule-3 grabbing non-integrin homologue-related 3 (SIGNR3). Immunofluorescence assay (IFA) with the respective CLR hFc-fusions against whole P. murina life forms corroborated these findings. Lastly, we surveyed the mRNA expression profiles of the respective CLRs tested above in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model and determined that macrophage galactose type C-type lectin (Mgl-1), implicated in recognizing terminal N-acetylgalactosamine (GalNAc) found in the glycoproteins of microbial pathogens was significantly up-regulated during infection.
Conclusion. The data herein add to the growing list of CLRs recognizing Pneumocystis and provide insights for further study of organism/host immune cell interactions.
-
-
- Molecular and Microbial Epidemiology
-
-
-
Comparative analyses of clinical features reveal the severity of human adenovirus type 55 and type 7 in acute respiratory tract infections
Qing Zhu, Shuyan Chen, Li Gu and Jiuxin QuIntroduction. Human adenovirus (HAdV) is an important pathogen in acute respiratory tract infections (ARTIs) and HAdV genotypes are associated with disease severity.
Hypothesis. Comparative analyses of clinical features could reveal the severity of different HAdV genotypes in ARTIs.
Aim. This study aimed to investigate the molecular epidemiology of HAdV infections and explore the correlations between clinical features and HAdV genotypes.
Methodology. A retrospective study was conducted on ARTIs at Beijing Chao-Yang Hospital during the period 2011–2016. A standardized data form was used to record the clinical information. HAdV was detected by FQ-PCR from respiratory specimens, and genotypes were determined by entire hexon gene sequencing.
Results. A total of 8044 samples were collected, of which 296 (3.7 %) were HAdV-positive. Patients ≤44 years old were more likely to be positive for HAdV. There were three peak periods of adenoviral infections, with detection rates of 13.03, 9.39 and 10.38 %, respectively. Six HAdV genotypes (HAdV-55, -7, -3, -14, -50, -2) were identified, with HAdV-55 and HAdV-7 being the most prevalent (50.6 and 21.5 %). Compared with HAdV-7 and other types, patients infected with HAdV-55 had a longer duration of fever (P=0.0428). Infections with HAdV-55 and HAdV-7 were more severe compared to those caused by other types, with higher rates of oxygen therapy and mechanical ventilation (P=0.0172 and P=0.0144). All five deaths were caused by HAdV‐55.
Conclusion. This study describes the epidemiological characteristics of HAdV infections in North China, revealing the higher severity of HAdV-55 and HAdV-7 in ARTIs. Thus, strengthened surveillance of HAdV genotypes is warranted.
-
-
- Pathogenesis, Virulence and Host Response
-
-
-
VicRK and CovR polymorphisms in Streptococcus mutans strains associated with cardiovascular infections
Introduction. Streptococcus mutans , a common species of the oral microbiome, expresses virulence genes promoting cariogenic dental biofilms, persistence in the bloodstream and cardiovascular infections.
Gap statement. Virulence gene expression is variable among S. mutans strains and controlled by the transcription regulatory systems VicRK and CovR.
Aim. This study investigates polymorphisms in the vicRK and covR loci in S. mutans strains isolated from the oral cavity or from the bloodstream, which were shown to differ in expression of covR, vicRK and downstream genes.
Methodology. The transcriptional activities of covR, vicR and vicK were compared by RT-qPCR between blood and oral strains after exposure to human serum. PCR-amplified promoter and/or coding regions of covR and vicRK of 18 strains (11 oral and 7 blood) were sequenced and compared to the reference strain UA159.
Results. Serum exposure significantly reduced covR and vicR/K transcript levels in most strains (P<0.05), but reductions were higher in oral than in blood strains. Single-nucleotide polymorphisms (SNPs) were detected in covR regulatory and coding regions, but SNPs affecting the CovR effector domain were only present in two blood strains. Although vicR was highly conserved, vicK showed several SNPs, and SNPs affecting VicK regions important for autokinase activity were found in three blood strains.
Conclusions. This study reveals transcriptional and structural diversity in covR and vicR/K, and identifies polymorphisms of functional relevance in blood strains, indicating that covR and vicRK might be important loci for S. mutans adaptation to host selective pressures associated with virulence diversity.
-
-
Volumes and issues
-
Volume 73 (2024)
-
Volume 72 (2023 - 2024)
-
Volume 71 (2022)
-
Volume 70 (2021)
-
Volume 69 (2020)
-
Volume 68 (2019)
-
Volume 67 (2018)
-
Volume 66 (2017)
-
Volume 65 (2016)
-
Volume 64 (2015)
-
Volume 63 (2014)
-
Volume 62 (2013)
-
Volume 61 (2012)
-
Volume 60 (2011)
-
Volume 59 (2010)
-
Volume 58 (2009)
-
Volume 57 (2008)
-
Volume 56 (2007)
-
Volume 55 (2006)
-
Volume 54 (2005)
-
Volume 53 (2004)
-
Volume 52 (2003)
-
Volume 51 (2002)
-
Volume 50 (2001)
-
Volume 49 (2000)
-
Volume 48 (1999)
-
Volume 47 (1998)
-
Volume 46 (1997)
-
Volume 45 (1996)
-
Volume 44 (1996)
-
Volume 43 (1995)
-
Volume 42 (1995)
-
Volume 41 (1994)
-
Volume 40 (1994)
-
Volume 39 (1993)
-
Volume 38 (1993)
-
Volume 37 (1992)
-
Volume 36 (1992)
-
Volume 35 (1991)
-
Volume 34 (1991)
-
Volume 33 (1990)
-
Volume 32 (1990)
-
Volume 31 (1990)
-
Volume 30 (1989)
-
Volume 29 (1989)
-
Volume 28 (1989)
-
Volume 27 (1988)
-
Volume 26 (1988)
-
Volume 25 (1988)
-
Volume 24 (1987)
-
Volume 23 (1987)
-
Volume 22 (1986)
-
Volume 21 (1986)
-
Volume 20 (1985)
-
Volume 19 (1985)
-
Volume 18 (1984)
-
Volume 17 (1984)
-
Volume 16 (1983)
-
Volume 15 (1982)
-
Volume 14 (1981)
-
Volume 13 (1980)
-
Volume 12 (1979)
-
Volume 11 (1978)
-
Volume 10 (1977)
-
Volume 9 (1976)
-
Volume 8 (1975)
-
Volume 7 (1974)
-
Volume 6 (1973)
-
Volume 5 (1972)
-
Volume 4 (1971)
-
Volume 3 (1970)
-
Volume 2 (1969)
-
Volume 1 (1968)