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1.
Case Rep Infect Dis ; 2021: 6638780, 2021.
Article in English | MEDLINE | ID: mdl-34007495

ABSTRACT

BACKGROUND: Hypervirulent Klebsiella pneumoniae causes severe disseminated infections, typically with hepatic and central nervous system involvement including endophthalmitis. Case Presentation. We report a fatal case of an undocumented Chinese migrant in her 60s who presented to the emergency department with abdominal pain, lethargy, and headache over the preceding two weeks. She had a new diagnosis of diabetes mellitus on admission. Computed tomography scan of the thorax, abdomen, and pelvis showed bilateral pneumonia with liver abscesses. The patient was treated with empirical broad-spectrum antibiotics before K. pneumoniae was isolated from cerebrospinal fluid and blood cultures. The isolate was further characterised as a ST23 (ST: sequence type), serotype K1 hypervirulent strain using Nanopore sequencing. Despite admission to the intensive care unit, the patient died within 48 hrs of admission. CONCLUSIONS: This case demonstrates the need for increased awareness of hypervirulent K. pneumoniae, even in countries where it occurs infrequently. Novel, rapid, sequencing technologies can support diagnosis in unusual presentations.

2.
J Hosp Infect ; 103(1): 35-43, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31132394

ABSTRACT

AIM: To describe the investigation and management of a meticillin-resistant Staphylococcus aureus (MRSA) outbreak on a neonatal intensive care unit (NICU) and the lessons learnt. METHODS: This was an outbreak report and case-control study conducted in a 40-cot NICU in a tertiary referral hospital and included all infants colonized/infected with gentamicin-resistant MRSA. INTERVENTION: Standard infection-control measures including segregation of infants, barrier precautions, enhanced cleaning, assessment of staff practice including hand hygiene, and increased MRSA screening of infants were implemented. Continued MRSA acquisitions led to screening of all NICU staff. A case-control study was performed to assess staff contact with colonized babies and inform the management of the outbreak. FINDINGS: Eight infants were colonized with MRSA (spa type t2068), one of whom subsequently developed an MRSA bacteraemia. MRSA colonization was significantly associated with lower gestational age; lower birthweight and with being a twin. Three nurses were MRSA colonized but only one nurse (45) was colonized with MRSA spa type t2068. Multivariable logistic regression analysis identified being cared for by nurse 45 as an independent risk factor for MRSA colonization. CONCLUSIONS: Lack of accurate recording of which nurses looked after which infants (and when) made identification of the risk posed by being cared for by particular nurses difficult. If this had been clearer, it may have enabled earlier identification of the colonized nurse, avoiding subsequent cases. This study highlights the benefit of using a case-control study, which showed that most nurses had no association with colonized infants.


Subject(s)
Carrier State/epidemiology , Disease Outbreaks , Intensive Care Units, Neonatal , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Staphylococcal Infections/epidemiology , Carrier State/microbiology , Carrier State/prevention & control , Carrier State/transmission , Case-Control Studies , Disease Transmission, Infectious/prevention & control , Female , Humans , Infant , Infant, Newborn , Infection Control/methods , Male , Methicillin-Resistant Staphylococcus aureus/classification , Staphylococcal Infections/microbiology , Staphylococcal Infections/prevention & control , Staphylococcal Infections/transmission , Tertiary Care Centers
3.
J Hosp Infect ; 100(1): 35-39, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29969691

ABSTRACT

Infections with carbapenemase-producing Enterobacteriaceae (CPE) and vancomycin-resistant enterococci (VRE) are associated with increased morbidity and mortality, but the carriage rates of CRE and VRE among hospital inpatients are unknown. A point-prevalence survey was conducted to determine CPE and VRE carriage rates in hospitalized adults. Eight hundred and eighteen of 960 (85.2%) adult inpatients were invited to participate in the study. Of these, 595 patients (72.7%) consented and provided specimens. Of 540 samples tested, none were positive for CPE. One hundred and thirty of 540 (24.1%) samples were VRE positive, and 34 of 40 (85%) of wards had cases. Universal screening for CPE may not be cost-effective in low-prevalence settings, but targeted screening of high-risk patients should continue. The optimal screening strategy for VRE remains to be determined, as universal screening and isolation is not feasible in the study setting.


Subject(s)
Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Carrier State/epidemiology , Enterobacteriaceae Infections/epidemiology , Gram-Positive Bacterial Infections/epidemiology , Vancomycin-Resistant Enterococci/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Carrier State/microbiology , Enterobacteriaceae Infections/microbiology , Female , Gram-Positive Bacterial Infections/microbiology , Hospitals, University , Humans , Inpatients , Male , Middle Aged , Prevalence , Surveys and Questionnaires , United Kingdom/epidemiology , Young Adult
4.
Clin Pharmacol Ther ; 103(3): 449-457, 2018 03.
Article in English | MEDLINE | ID: mdl-28160272

ABSTRACT

A placebo-controlled trial that compares the outcomes of immediate vs. deferred initiation of antiretroviral therapy in HIV +ve tuberculous meningitis (TBM) patients was conducted in Vietnam in 2011. Here, the pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol were investigated in the presence and absence of anti-HIV treatment in 85 patients. Pharmacokinetic analyses show that HIV therapy has no significant impact on the pharmacokinetics of TB drugs in this cohort. The same population, however, displayed generally low cerebrospinal fluid (CSF) and systemic exposures to rifampicin compared to previously reported HIV -ve cohorts. Elevated CSF concentrations of pyrazinamide, on the other hand, were strongly and independently correlated with increased mortality and neurological toxicity. The findings suggest that the current standard dosing regimens may put the patient at risk of treatment failure from suboptimal rifampicin exposure, and potentially increasing the risk of adverse central nervous system events that are independently correlated with pyrazinamide CSF exposure.


Subject(s)
Antiretroviral Therapy, Highly Active/adverse effects , Antitubercular Agents/therapeutic use , HIV Seropositivity/complications , Tuberculosis, Meningeal/complications , Tuberculosis, Meningeal/drug therapy , Adult , Aged , Antitubercular Agents/pharmacokinetics , Coinfection , Double-Blind Method , Drug Interactions , Female , HIV Seropositivity/mortality , Humans , Male , Middle Aged , Neurotoxicity Syndromes/epidemiology , Neurotoxicity Syndromes/metabolism , Survival Analysis , Treatment Failure , Tuberculosis, Meningeal/mortality
5.
Article in English | MEDLINE | ID: mdl-29276617

ABSTRACT

Antimicrobial resistance (AMR) is a global public health threat. Emergence of AMR occurs naturally, but can also be selected for by antimicrobial exposure in clinical and veterinary medicine. Despite growing worldwide attention to AMR, there are substantial limitations in our understanding of the burden, distribution and determinants of AMR at the population level. We highlight the importance of population-based approaches to assess the association between antimicrobial use and AMR in humans and animals. Such approaches are needed to improve our understanding of the development and spread of AMR in order to inform strategies for the prevention, detection and management of AMR, and to support the sustainable use of antimicrobials in healthcare.

6.
Article in English | MEDLINE | ID: mdl-29869630

ABSTRACT

[This corrects the article DOI: 10.1017/gheg.2017.4.].

7.
Clin Microbiol Infect ; 21(8): 779-85, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26033668

ABSTRACT

Staphylococcus aureus bacteraemia (SAB) is a common, serious infection that is associated with high rates of morbidity and mortality. Evidence suggests that infectious disease consultation (IDC) improves clinical management in patients with SAB. We examined whether the introduction of a routine bedside IDC service for adults with SAB improved clinical management and outcomes compared to telephone consultation. We conducted an observational cohort study of 571 adults with SAB at a teaching hospital in the United Kingdom between July 2006 and December 2012. A telephone consultation was provided on the day of positive blood culture in all cases, but an additional bedside IDC was provided after November 2009 (routine IDC group). Compared to patients in the pre-IDC group, those in the routine IDC group were more likely to have a removable focus of infection identified, echocardiography performed and follow-up blood cultures performed. They also received longer courses of antimicrobial therapy, were more likely to receive combination antimicrobial therapy and were more likely to have SAB recorded in the hospital discharge summary. There was a trend towards lower mortality at 30 days in the routine IDC group compared to the pre-IDC group (12% vs. 22%, p 0.07). Our findings suggest that routine bedside IDC should become the standard of care for adults with SAB.


Subject(s)
Bacteremia/diagnosis , Bacteremia/drug therapy , Referral and Consultation/statistics & numerical data , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Staphylococcus aureus/isolation & purification , Adult , Aged , Aged, 80 and over , Bacteremia/mortality , Cohort Studies , Female , Hospitals, Teaching , Humans , Male , Middle Aged , Staphylococcal Infections/mortality , Survival Analysis , Treatment Outcome , United Kingdom , Young Adult
8.
Br Med Bull ; 113(1): 117-31, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25693576

ABSTRACT

INTRODUCTION: Tuberculous meningitis (TBM) is the most severe form of infection caused by Mycobacterium tuberculosis, causing death or disability in more than half of those affected. The aim of this review is to examine recent advances in our understanding of TBM, focussing on the diagnosis and treatment of this devastating condition. SOURCES OF DATA: Papers on TBM published between 1891 and 2014 and indexed in the NCBI Pubmed. The following search terms were used: TBM, diagnosis, treatment and outcome. AREAS OF AGREEMENT: The diagnosis of TBM remains difficult as its presentation is non-specific and may mimic other causes of chronic meningoencephalitis. Rapid recognition of TBM is crucial, however, as delays in initiating treatment are associated with poor outcome. The laboratory diagnosis of TBM is hampered by the low sensitivity of cerebrospinal fluid microscopy and the slow growth of M. tuberculosis in conventional culture systems. The current therapy of TBM is based on the treatment of pulmonary tuberculosis, which may not be ideal. The combination of TBM and HIV infection poses additional management challenges because of the need to treat both infections and the complications associated with them. AREAS OF CONTROVERSY: The pathogenesis of TBM remains incompletely understood limiting the development of interventions to improve outcome. The optimal therapy of TBM has not been established in clinical trials, and increasing antimicrobial resistance threatens successful treatment of this condition. The use of adjunctive anti-inflammatory agents remains controversial, and their mechanism of action remains incompletely understood. The role of surgical intervention is uncertain and may not be available in areas where TBM is common. GROWING POINTS: Laboratory methods to improve the rapid diagnosis of TBM are urgently required. Clinical trials of examining the use of high-dose rifampicin and/or fluoroquinolones are likely to report in the near future. AREAS TIMELY FOR DEVELOPING RESEARCH: The use of biomarkers to improve the rapid diagnosis of TBM warrants further investigation. The role of novel antituberculosis drugs, such as bedaquiline and PA-824, in the treatment of TBM remains to be explored. Human genetic polymorphisms may explain the heterogeneity of response to anti-inflammatory therapies and could potentially be used to tailor therapy.


Subject(s)
Antitubercular Agents/administration & dosage , Drug Therapy, Combination/methods , Mycobacterium tuberculosis/drug effects , Tuberculosis, Meningeal/drug therapy , Host-Pathogen Interactions , Humans , Isoniazid/administration & dosage , Mycobacterium tuberculosis/physiology , Practice Guidelines as Topic , Pyrazinamide/administration & dosage , Rifampin/administration & dosage , Treatment Outcome , Tuberculosis, Meningeal/genetics , Tuberculosis, Meningeal/microbiology
9.
J Antimicrob Chemother ; 69(4): 907-10, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24284779

ABSTRACT

OBJECTIVES: There are limited data available on the epidemiology and prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the human population that encode the recently described mecA homologue, mecC. To address this knowledge gap we undertook a prospective prevalence study in England to determine the prevalence of mecC among MRSA isolates. PATIENTS AND METHODS: Three hundred and thirty-five sequential MRSA isolates from individual patients were collected from each of six clinical microbiology laboratories in England during 2011-12. These were tested by PCR or genome sequencing to differentiate those encoding mecA and mecC. mecC-positive isolates were further characterized by multilocus sequence typing, spa typing, antimicrobial susceptibility profile and detection of PBP2a using commercially available kits. RESULTS: Nine out of the 2010 MRSA isolates tested were mecC positive, indicating a prevalence among MRSA in England of 0.45% (95% CI 0.24%-0.85%). The remainder were mecA positive. Eight out of these nine mecC MRSA isolates belonged to clonal complex 130, the other being sequence type 425. Resistance to non-ß-lactam antibiotics was rare among these mecC MRSA isolates and all were phenotypically identified as MRSA using oxacillin and cefoxitin according to BSAC disc diffusion methodology. However, all nine mecC isolates gave a negative result using three different commercial PBP2a detection assays. CONCLUSIONS: mecC MRSA are currently rare among MRSA isolated from humans in England and this study provides an important baseline prevalence rate to monitor future changes, which may be important given the increasing prevalence of mecC MRSA reported in Denmark.


Subject(s)
Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , DNA, Bacterial/genetics , England/epidemiology , Genes, Bacterial , Genotype , Humans , Molecular Epidemiology , Molecular Typing , Polymerase Chain Reaction , Prevalence , Prospective Studies , Sequence Analysis, DNA
12.
Curr Opin Microbiol ; 15(5): 583-7, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23022568

ABSTRACT

Acquisition of exogenous DNA by pathogenic bacteria represents the basis for much of the acquired antimicrobial resistance in pathogenic bacteria. A more extreme mechanism to avoid the effect of an antibiotic is to delete the drug target, although this would be predicted to be rare since drug targets are often essential genes. Here, we review and discuss the description of a novel mechanism of resistance to the cephalosporin drug ceftazidime caused by loss of a penicillin-binding protein (PBP) in a Gram-negative bacillus (Burkholderia pseudomallei). This organism causes melioidosis across south-east Asia and northern Australia, and is usually treated with two or more weeks of ceftazidime followed by oral antibiotics for three to six months. Comparison of clinical isolates from six patients with melioidosis found initial ceftazidime-susceptible isolates and subsequent ceftazidime-resistant variants. The latter failed to grow on commonly used culture media, rendering these isolates difficult to detect in the diagnostic laboratory. Genomic analysis using pulsed-field gel electrophoresis and array based genomic hybridisation revealed a large-scale genomic deletion comprising 49 genes in the ceftazidime-resistant strains. Mutational analysis of wild-type B. pseudomallei demonstrated that ceftazidime resistance was due to deletion of a gene encoding a PBP 3 present within the region of genomic loss. This provides one explanation for ceftazidime treatment failure, and may be a frequent but undetected event in patients with melioidosis.


Subject(s)
Anti-Bacterial Agents/pharmacology , Burkholderia pseudomallei/genetics , Ceftazidime/pharmacology , Drug Resistance, Bacterial , Gene Deletion , Penicillin-Binding Proteins/genetics , Anti-Bacterial Agents/administration & dosage , Burkholderia pseudomallei/classification , Burkholderia pseudomallei/isolation & purification , Ceftazidime/administration & dosage , Comparative Genomic Hybridization , DNA Mutational Analysis , Electrophoresis, Gel, Pulsed-Field , Humans , Melioidosis/drug therapy , Melioidosis/microbiology , Molecular Typing
13.
J Antimicrob Chemother ; 67(10): 2307-8, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22729921

ABSTRACT

The ability to perform rapid, high-throughput whole-genome sequencing using bench-top platforms represents a step-change in capabilities for diagnostic and public health microbiology laboratories. As the cost of sequencing continues to decline, the challenge will be to define when and where to apply this technology. This article reviews its potential applications in the clinical microbiology laboratory and discusses the current barriers to implementation.


Subject(s)
Bacteria/genetics , Bacterial Infections/diagnosis , Bacterial Infections/microbiology , Bacteriological Techniques/methods , DNA, Bacterial/chemistry , Genome, Bacterial , High-Throughput Nucleotide Sequencing/methods , Bacteria/classification , Bacteria/isolation & purification , Bacteriological Techniques/trends , DNA, Bacterial/genetics , Humans
14.
Eye (Lond) ; 14(Pt 6): 889-91, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11584849

ABSTRACT

BACKGROUND: Chronic infection with the hepatitis C virus has been reported to cause a wide variety of ophthalmic lesions. The incidence and significance of these lesions in an unselected population has not been assessed. METHODS: We studied a group of unselected patients with chronic hepatitis C and performed a full ophthalmic examination on each. As a control group we studied patients with chronic hepatitis B infection. RESULTS: In 25 patients with chronic hepatitis C we found no increase in the prevalence of significant ocular disease when compared with a cohort of patients with chronic hepatitis B. CONCLUSION: Chronic heptatitis C does not cause any marked increase in the incidence of ocular disease.


Subject(s)
Eye Diseases/epidemiology , Hepatitis C, Chronic/epidemiology , Adult , Aged , Comorbidity , Female , Humans , Male , Middle Aged , Prospective Studies , United Kingdom/epidemiology
16.
J Hepatol ; 31 Suppl 1: 152-9, 1999.
Article in English | MEDLINE | ID: mdl-10622579

ABSTRACT

The known mechanisms of hepatitis C virus (HCV) clearance and their failure in persistent infection are discussed. Interferon-alpha is the main treatment in chronic HCV but has shown poor sustained virological response rates when used as a monotherapy. The effects of interferon-a may include inhibition of HCV virion production by an effect on viral RNA and protein synthesis, enhancement of immune lysis of HCV infected cells, inhibition of hepatic fibrosis by an effect on TGFbeta, and an effect on HCV induced carcinogenesis. Mathematical modelling studies have provided insights into the mechanisms of action of interferon-alpha in chronic HCV. The two-phase plasma HCV RNA disappearance curve may reflect the presence of an interferon-resistant second site of HCV replication either within or outside the liver. Clinical observations and cerebral magnetic resonance scans provide evidence of functional cerebral impairment in HCV infected patients, raising the issue of the central nervous system (CNS) as a site for HCV replication. Recent studies using ribavirin in combination with interferon suggest that this approach doubles the sustained response rates obtained without having a major effect on the initial rate of HCV clearance (see Zeuzem paper). The potential mechanisms of action of ribavirin, although not yet fully understood, include inhibition of synthesis of GTP by an effect on inosine monophosphate dehydrogenase thereby limiting viral RNA synthesis, and enhancement of TH1 responses, which may assist viral clearance. There is no significant effect on HCV RNA polymerase activity. It is possible that ribavirin may have activity at extrahepatic sites of HCV infection, thus explaining the marked reduction in relapse rates with combination therapy, without an appreciable effect on initial antiviral response.


Subject(s)
Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Interferon-alpha/pharmacology , Interferon-alpha/therapeutic use , Hepacivirus/physiology , Humans , Models, Theoretical , Ribavirin/therapeutic use , Treatment Failure , Virus Replication
17.
Nat Med ; 1(4): 374-5, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7585070

ABSTRACT

Severe malaria is a major cause of childhood mortality in sub-Saharan Africa but the factors predisposing children to severe forms of malaria have not been fully elucidated. In a case-control study of over 1,200 Gambian children hepatitis B virus carriage was significantly increased amongst cases of severe malaria compared to matched controls. We suggest that this association may relate to impaired clearance of liver stage parasites in the presence of the reduced level of HLA class I antigen expression on hepatocytes infected by hepatitis B virus. If this association is causal and viral carriage predisposes to severe malaria, widespread vaccination against hepatitis B virus may reduce mortality from severe malaria.


Subject(s)
Carrier State , Hepatitis B Surface Antigens/blood , Hepatitis B virus/immunology , Hepatitis B/complications , Malaria, Cerebral/complications , Malaria, Falciparum/complications , Animals , Carrier State/epidemiology , Carrier State/immunology , Case-Control Studies , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Gambia/epidemiology , Hepatitis B/epidemiology , Hepatitis B/immunology , Humans , Liver/parasitology , Liver/virology , Malaria, Cerebral/epidemiology , Malaria, Cerebral/immunology , Malaria, Falciparum/epidemiology , Malaria, Falciparum/immunology , Odds Ratio , Plasmodium falciparum/physiology , Prevalence
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