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Biomedical subjects

David R Murdoch

Publications and source records attributed to David R Murdoch.

36 records · Page 2Linked to original sources

Successful antimicrobial therapy and implant retention for streptococcal infection of prosthetic joints.

BACKGROUND: Streptococci cause up to 20% of prosthetic joint infections but this has received little attention in the published literature. METHODS: We reviewed retrospectively our experience with treatment of streptococcal prosthetic joint infections. Patients were followed up for up to 15 years after discontinuation of antimicrobial therapy and up to 8.5 years while on continuous antimicrobial therapy. RESULTS: Eighteen cases were diagnosed between 1984 and 1995. These included one group A, seven group B, one group D, seven group G and one viridans-group streptococcal infection as well as one group B and D streptococcal co-infection. All were late-onset infections and most (11 of 18, 61%) were acute. Hip and knee joints were equally affected. Six of seven group G streptococcal infections were associated with skin or soft tissue infections. Sixteen patients were treated primarily with antimicrobial agents including 5 days to 6 weeks given intravenously and 2 weeks to 8.5 years given orally. At latest follow up, 10 patients had been off antimicrobial therapy for at least 18 months without relapse, one patient had been off antimicrobial therapy for 7 months without relapse and four infections were successfully controlled with long-term suppressive antimicrobial therapy. One infection was unable to be controlled with antimicrobial therapy. CONCLUSIONS: Our results, and those of others, show that prosthetic joint infections caused by streptococci have a relatively good outcome with primary antimicrobial therapy and, when necessary, drainage, lavage or debridement. Provided the prosthesis is stable and the patient can tolerate long-term antimicrobial therapy, this may be an effective alternative to excision arthroplasty.

Adult↗

The etiology of febrile illness in adults presenting to Patan hospital in Kathmandu, Nepal.

In Nepal, many infections remain poorly characterized, partly due to limited diagnostic facilities. We studied consecutive febrile adults presenting to a general hospital in Kathmandu, Nepal. Of the 876 patients enrolled, enteric fever and pneumonia were the most common clinical diagnoses. Putative pathogens were identified in 323 (37%) patients, the most common being Salmonella enterica serotype Typhi and S. enterica serotype Paratyphi A (117), Rickettsia typhi (97), Streptococcus pneumoniae (53), Leptospira spp. (36), and Orientia tsutsugamushi (28). Approximately half of the Salmonella isolates were resistant to nalidixic acid. No clinical predictors were identified to reliably distinguish between the different infections. These findings confirm the heavy burden of enteric fever and pneumonia in Kathmandu, and highlight the importance of murine typhus, scrub typhus, and leptospirosis. Given the lack of reliable clinical predictors, the development of cheap and accurate diagnostic tests are likely to be of great clinical utility in this setting.

Adolescent↗

High-altitude illness.

High-altitude illness is the collective term for acute mountain sickness (AMS), high-altitude cerebral oedema (HACE), and high-altitude pulmonary oedema (HAPE). The pathophysiology of these syndromes is not completely understood, although studies have substantially contributed to the current understanding of several areas. These areas include the role and potential mechanisms of brain swelling in AMS and HACE, mechanisms accounting for exaggerated pulmonary hypertension in HAPE, and the role of inflammation and alveolar-fluid clearance in HAPE. Only limited information is available about the genetic basis of high-altitude illness, and no clear associations between gene polymorphisms and susceptibility have been discovered. Gradual ascent will always be the best strategy for preventing high-altitude illness, although chemoprophylaxis may be useful in some situations. Despite investigation of other agents, acetazolamide remains the preferred drug for preventing AMS. The next few years are likely to see many advances in the understanding of the causes and management of high-altitude illness.

Acetazolamide↗

Nucleic acid amplification tests for the diagnosis of pneumonia.

Molecular diagnostic techniques, such as polymerase chain reaction (PCR), are promising tools for the rapid etiological diagnosis of pneumonia. PCR offers potential advantages over conventional tests for the detection of Mycoplasma pneumoniae, Legionella species, and Chlamydia pneumoniae. For pneumococcal pneumonia in adults, PCR adds little to existing diagnostic tests and is unable to distinguish pneumococcal colonization from infection when testing respiratory samples. Although PCR is probably more sensitive than are conventional microscopy-based methods for diagnosing Pneumocystis carinii pneumonia, the specificity is uncertain, because P. carinii can occasionally be detected in the absence of clinical symptoms. PCR is useful for the diagnosis of viral pneumonia in immunocompromised patients. Further work is required to better characterize the role of PCR versus the role of other tests for diagnosing pneumonia and to develop standard PCR assays that can be readily adopted by routine diagnostic laboratories.

Bacterial Typing Techniques↗

Evaluation of a PCR assay for detection of Streptococcus pneumoniae in respiratory and nonrespiratory samples from adults with community-acquired pneumonia.

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia, but it is undoubtedly underdiagnosed. We used a nested PCR assay (targeting the pneumolysin gene) to detect S. pneumoniae DNA in multiple sample types from 474 adults with community-acquired pneumonia and 183 control patients who did not have pneumonia. Plasma or buffy coat samples were PCR positive in only 6 of the 21 patients with positive blood cultures for S. pneumoniae and in 12 other patients (4 of whom had no other laboratory evidence of S. pneumoniae infection). Buffy coat samples from two control patients (neither having evidence of S. pneumoniae infection), but no control plasma samples, were PCR positive. Although pneumococcal antigen was detected in the urine from 120 of 420 (29%) patients, only 4 of 227 (2%) urine samples tested were PCR positive. Overall, 256 of 318 (81%) patients had PCR-positive sputum samples, including 58 of 59 samples from which S. pneumoniae was cultured. Throat swab samples from 229 of 417 (55%) patients were PCR positive and, in those who produced sputum, 96% also had positive PCR results from sputum. Throat swabs from 73 of 126 (58%) control patients were also PCR positive. We conclude that the pneumolysin PCR assay adds little to existing diagnostic tests for S. pneumoniae and is unable to distinguish colonization from infection when respiratory samples are tested.

Adult↗

Failure to genotype herpes simplex virus by real-time PCR assay and melting curve analysis due to sequence variation within probe binding sites.

Real-time PCR with melting curve analysis of PCR products is a rapid procedure for detecting and genotyping herpes simplex virus (HSV). When testing mucocutaneous samples for HSV by a real-time PCR assay targeting the DNA polymerase gene, we found that some PCR products had atypical melting curves that did not conform to the expected melting temperatures for HSV type 1 or 2. Sequence analysis showed that these strains had base-pair mismatches over the probe binding sites. An alternative assay is required to type such atypical isolates.

Base Pair Mismatch↗

Comparison of microscan broth microdilution, synergy quad plate agar dilution, and disk diffusion screening methods for detection of high-level aminoglycoside resistance in enterococcus species.

We compared the dried MicroScan microdilution panel, Synergy Quad plate agar dilution, and high-potency disk diffusion screening methods for the detection of high-level aminoglycoside resistance in 815 enterococcal bloodstream isolates. Agreement between the three methods was 99% when testing for high-level gentamicin resistance and 96% when testing for high-level streptomycin resistance.

Anti-Bacterial Agents↗

Diagnosis of Legionella infection.

Legionellae, which are important causes of pneumonia in humans, continue to be incorrectly labeled as exotic pathogens. The ability to diagnose Legionella infection is limited by the nonspecific nature of clinical features and the shortcomings of diagnostic tests. Despite recent improvements, existing diagnostic tests for Legionella infection either lack sensitivity for detecting all clinically important legionellae or are unable to provide results within a clinically useful time frame. Understanding local Legionella epidemiology is important for making decisions about whether to test for Legionella infection and which diagnostic tests to use. In most situations, the use of both the urinary antigen test plus sputum culture is the best diagnostic combination. Polymerase chain reaction (PCR) is a promising tool, but standardized assays are not commercially available. Further work needs to focus on the development of urinary antigen tests assays that detect a wider range of pathogenic legionellae and on the development of standardized PCR assays.

Antigens, Bacterial↗

Sequential emergence of antibiotic resistance in enterococcal bloodstream isolates over 25 years.

We determined the antibiotic susceptibilities of 1,785 enterococcal bloodstream isolates collected over 25 years. Antibiotic resistance emerged at a greater rate in Enterococcus faecium than in other enterococcal species, and E. faecium isolates became proportionally more common over time. Our findings confirm the pattern of emerging antibiotic resistance among enterococci and highlight the increasing importance of E. faecium as a cause of bloodstream infection.

Colorado↗

Molecular genetic methods in the diagnosis of lower respiratory tract infections.

Molecular diagnostic techniques, such as PCR, have become useful tools for the rapid etiological diagnosis of lower respiratory tract infections. Nucleic acid amplification tests (NAATs) have been evaluated for detecting most respiratory pathogens, and commercial assays are available for some pathogens. However, standardized protocols are needed before these assays are introduced into routine diagnostic use. For pneumonia, NAATs offer advantages over conventional tests for the detection of Mycoplasma pneumoniae, Legionella spp. and Chlamydia pneumoniae. For pneumococcal pneumonia in adults, PCR adds little to existing diagnostic tests, and is unable to distinguish pneumococcal colonization from infection when testing respiratory samples. Although less sensitive than culture-based methods, several commercial molecular diagnostic assays have been developed for tuberculosis and are useful rapid tests for selected patients. PCR can now be considered the rapid diagnostic test of choice for pertussis and some respiratory virus infections. Further work is required to better characterize the role of molecular diagnostic tests for diagnosing lower respiratory tract infections, and to develop standard assays that can be readily adopted by routine diagnostic laboratories.

Bacterial Infections↗