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1.
JAC Antimicrob Resist ; 6(3): dlae079, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38817948

ABSTRACT

Background: New dosing regimens for ceftriaxone 4 g/24 hours and ceftazidime 3 g/12 hours are convenient for patients receiving OPAT. To date, these have not been clinically validated. Aim: To assess the tolerability, toxicity and effectiveness of once daily ceftriaxone (4 g) and 12 hourly ceftazidime regimens (3 g twice a day) in the OPAT setting. Patients and methods: From April 2018 until March 2023; demographic, clinical, microbiological and outcome data were collected on all adult patients discharged to a community-based OPAT team in East London. Results: There were 487 OPAT episodes. Fifty-three (10.9%) patients received ceftriaxone 4 g once a day and 20 (4.1%) ceftazidime 3 g twice a day. In the ceftriaxone group, the commonest conditions treated were orthopaedic, neurosurgical or diabetic foot infections. OPAT was used to expedite the discharge of 45 (84.9%) patients, the remainder were admission avoidance episodes. The commonest isolate causing infection was MSSA 23 (43.4%). There were no tolerability or toxicity episodes recorded. All patients were cured and bed days saved were 1266.In the smaller twice-daily ceftazidime cohort, seven (35%) patients were treated for necrotizing otitis externa, six (30%) for bronchiectasis and six (30%) for urinary tract infections. The commonest cause of infection was P. aeruginosa, 18 (90%). One case of nephrotoxicity was recorded. All patients were cured and bed days saved were 896. Conclusions: Regimens of ceftriaxone 4 g once a day and ceftazidime 3 g twice a day were well tolerated and highly effective. If widely adopted, these regimens will save OPAT and nursing time and enable more patients to be treated.

3.
Infect Prev Pract ; 5(3): 100298, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37534297

ABSTRACT

Objectives: To investigate the clinical, microbiological characteristics and outcomes of patients with bloodstream infections (BSI) due to carbapenemase-producing Enterobacterales (CPE). Methods: A multicentre retrospective observational study of patients with BSIs due to CPE admitted to six UK hospitals was conducted between 2011 and 2021. Multivariate analysis was used to identify factors predicting 30-day case fatality rate (CFR). Results: There were 84 episodes of CPE-BSIs, 37 (44%) due to OXA-48, 35 (42%) to metallo-betalactamases (MBL) and 12 (14%) to KPC. 63% of patients were male with a median age of 64 years. Common organisms included Klebsiella spp. (61%), Escherichia coli (20%) and Enterobacter spp. (13%). Urinary devices were more often involved in OXA-48 BSIs (12/37; 32%) compared to infections caused by MBL and KPC (4/35; 11% and 1/12; 8%; P = 0.046). In contrast, central venous catheters were more frequently present in KPC-BSIs (10/12; 92%) compared with OXA-48 and MBL (11/37; 30% and 20/35; 57%; P = 0.002). Effective definitive antimicrobials were received by 72/84 (86%) patients, comprising monotherapy (32/72; 44%) or combination therapy (40/72; 56%). 30-day case fatality rate (CFR) was 38%. Sepsis or septic shock was associated with death [OR 3.81 (CI 1.19-12.14), P = 0.024]. Conclusion: Strategies targeting high-risk patients and adherence to infection prevention bundles for urinary devices and central venous catheters can reduce OXA-48 and KPC-BSIs. Early recognition and management of severe sepsis, prompt initiation of appropriate antimicrobial therapy and development of novel antimicrobials are crucial to mitigate the high CFR associated with CPE-BSIs.

4.
Infect Prev Pract ; 5(2): 100280, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37095752

ABSTRACT

Introduction: Until recently, healthcare-associated E. coli bacteraemia was a neglected area of infection prevention and control (IPC), despite a 30-day mortality of 15-20%. Recently, the UK Department of Health (DH) introduced a target to reduce hospital-acquired E. coli bacteraemias by 50% over a five-year period. Following implementation of multifaceted and multidisciplinary interventions, the aim of this study was to determine its impact on achieving this target. Methods: From April 2017 to March 2022, consecutive hospital-acquired E. coli bacteraemic inpatients within Barts Health NHS Trust were prospectively studied. Using quality improvement methodology, and implementing the plan, do, study, act (PDSA) cycle at each stage, antibiotic prophylaxis for high-risk procedures were modified and 'good practice' interventions around medical devices introduced. Characteristics of bacteraemic patients were analysed and trends in bacteraemic episodes recorded. Statistical analysis was undertaken in Stata SE (version 16). Results: There were 770 patients and 797 episodes of hospital-acquired E. coli bacteraemias. Following a baseline of 134 episodes in 2017-18, this peaked at 194 in 2019-20 before dropping to 157 in 2020-21 and 159 in 2021-22. Most hospital-acquired E. coli bacteraemias occurred in those aged > 50, 551 (69.1%), with the highest proportion occurring in those age > 70, 292 (36.6%). Hospital-acquired E. coli bacteraemia occurred more commonly between October to December.Most episodes occurred in either medicine or care of the elderly patients, 345 (43.3%), specialist surgery, 141 (17.7%), haematology/oncology, 127 (15.9%) and patients requiring critical care, 108 (13.6%). The urinary tract, 336 (42.2%), both catheter and non-catheter associated, was the commonest sites of infection. 175 (22.0%) of E. coli bacteraemic isolates were extended spectrum beta lactamase (ESB) producing. Co-amoxiclav resistance was 315 (39.5%), ciprofloxacin resistance 246 (30.9%) and gentamicin resistance 123 (15.4%). At 7 days, 77 patients (9.7%; 95% CI 7.4-12.2%) died and by 30 days this had risen to 129 (16.2%; 95% CI 13.7-19.9%). Conclusion: Despite implementation of quality improvement (QI) interventions, it was not possible to achieve a 50% reduction from baseline although an 18% reduction was achieved from 2019-20 onwards. Our work highlights the importance of antimicrobial prophylaxis and medical device 'good practice'. Over time, these interventions, if properly implemented, could further reduce healthcare-associated E. coli bacteraemic infection.

5.
J Infect ; 84(1): 17-23, 2022 01.
Article in English | MEDLINE | ID: mdl-34706281

ABSTRACT

OBJECTIVES: To characterise and describe the diagnostic utility of Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) in intrathoracic tuberculosis in a cohort of patients with mediastinal lymphadenopathy of unknown aetiology. METHODS: Consecutive patients with intrathoracic lymphadenopathy undergoing EBUS-TBNA between 2012 and 2016 were identified. Demographic data, biopsy cytopathology and mycobacteriology results, HIV and vitamin D status, susceptibility results and final diagnoses were recorded. Pre- and post-procedure probability scores were assigned to each case to reflect the probability of tuberculosis. RESULTS: 315 cases were identified; 54 (17.1%) had tuberculosis and 261 (82.9%) had a non-tuberculosis diagnosis. amongst TB cases, the sensitivity of EBUS-TBNA was 59.3% (95% CI 45.06-72.14), specificity 100% (95% CI 98.19-100) and the negative predictive value (NPV) was 92.23% (95% CI 88.31-94.95). 19/54 (35%) TB cases were confirmed by EBUS mycobacterial culture and 13/54 (24.1%) by cytopathology.  33 (61.1%) of the TB cases, had a low to medium pre-test probability score assigned prior to EBUS-TBNA. Amongst EBUS culture-confirmed cases, we found a resistance rate of 10.5% to one or more first line TB drugs, with one case of multi-drug resistant TB. CONCLUSIONS: We confirmed the utility of EBUS-TBNA in the diagnosis of intrathoracic tuberculosis in an undifferentiated cohort of patients with mediastinal lymphadenopathy of unknown aetiology and advocate sending samples for mycobacterial culture in all cases in high tuberculosis incidence areas.


Subject(s)
Mediastinal Diseases , Tuberculosis, Lymph Node , Bronchoscopy , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Humans , London , Lymph Nodes/diagnostic imaging , Mediastinal Diseases/diagnosis , Retrospective Studies , Tuberculosis, Lymph Node/diagnosis
6.
J Med Virol ; 93(6): 3949-3954, 2021 06.
Article in English | MEDLINE | ID: mdl-33058290

ABSTRACT

BACKGROUND: Seasonal influenza is an annual occurrence that leads to large community outbreaks and increased hospitalization. A number of studies have suggested that influenza A (FLUAV) is associated with increased rates of hospitalization and mortality compared with influenza B (FLUBV). This study compared demographic and clinical variables in patients diagnosed with FLUAV or FLUBV during the 2017-2018 UK Influenza season. METHODS: Patient demographic and clinical information were obtained by accessing medical records of patients testing FLUAV or FLUBV positive using the Cepheid GXP. We used the χ2 test to compare variables in patients with laboratory-confirmed FLUAV and FLUBV. RESULTS: One hundred and twenty-seven adult patients had confirmed Influenza, 71 (55.9%) had FLUAV, and 56 (44.1%) FLUBV. There was no significant difference between severity at presentation, admission to HDU/ITU or median length of stay. The overall mortality was 6 (4.5%) and 9 (7.1%) at 7 and 30 days, respectively. There was a statistically significant difference in 7-day mortality between patients with FLUAV and FLUBV, 1 (1.4%) versus 5 (8.9%), respectively, p = .047) although this became nonsignificant at 30 days. CONCLUSIONS: With the exception of mortality, we did not observe significant differences between patients with FLUAV and FLUBV. Seven-day mortality in patients with FLUBV was significantly higher with FLUAV, although this was was not apparent at 30 days.


Subject(s)
Clinical Laboratory Techniques/statistics & numerical data , Influenza A virus/genetics , Influenza B virus/genetics , Influenza, Human/epidemiology , Influenza, Human/mortality , Adult , Aged , Aged, 80 and over , Disease Outbreaks , Female , Hospitalization/statistics & numerical data , Humans , Influenza, Human/diagnosis , Influenza, Human/virology , Male , Middle Aged , RNA, Viral/genetics , Retrospective Studies , Seasons , United Kingdom/epidemiology , Young Adult
7.
J Med Virol ; 93(6): 3934-3938, 2021 06.
Article in English | MEDLINE | ID: mdl-32869890

ABSTRACT

Annual outbreaks of seasonal influenza cause a substantial health burden. The aim of this study was to compare patient demographic/clinical data in two influenza patient groups presenting to hospital; those requiring O2 or critical care admission and those requiring less intensive treatment. The study was conducted from 1 December 2017 until 1 April 2019 at a district general hospital in East London. Patient demographic and clinical information was collected for all patients who had tested influenza positive by near-patient testing. χ2 test was used for categorical variables to see if there were significant differences for those admitted and the Wilcoxon rank-sum test to compare the length of inpatient stay. Of 127 patients, 56 (44.1%) required oxygen or critical care. There were significant increases in National Early Warning Score (NEWS) observations (P %3C .001), Charlson comorbidity index (P = .049), length of inpatient stay (P %3C .001), and a strong association with increasing age (P = .066) when the more intensive treatment group was compared with the less intensive treatment group. A total of 13 (18.3%) of 71 patients not requiring oxygen or critical care were not admitted to the hospital. Following rapid influenza testing, NEWS scores, comorbidities, and age should be incorporated into a decision tool in Accident and Emergency to aid hospital admission or discharge decisions.


Subject(s)
Hospitalization/statistics & numerical data , Hospitals, General/statistics & numerical data , Influenza, Human/diagnosis , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Influenza, Human/epidemiology , Intensive Care Units/statistics & numerical data , London , Male , Middle Aged , Patient Admission/standards , Risk Assessment , Time Factors , Triage/standards , Young Adult
8.
Perit Dial Int ; 39(2): 126-133, 2019.
Article in English | MEDLINE | ID: mdl-30739095

ABSTRACT

INTRODUCTION: The adoption of the International Society for Peritoneal Dialysis guideline of using mupirocin ointment has been limited by fear of developing mupirocin-resistant organisms. We performed a surveillance program of a large peritoneal dialysis (PD) unit. METHODS: We performed 1,175 surveillance swabs from anterior nares, PD catheter exit site, groin, and axilla, from 240 patients. The mean interval between swabs was 3.3 months. RESULTS: Colonization by Staphylococcus aureus (S. aureus) or Pseudomonas species was 9.5% and 10.9%, respectively. Despite adopting a universal policy of applying mupirocin to PD catheter exit sites in 2001, no instances of mupirocin-resistant S. aureus were identified. Moreover, patients who grew S. aureus from surveillance swabs did not experience higher peritonitis rates than those with "no growth." This was in contrast to patients who grew Pseudomonas or enteric organisms. There were no differences in patient demographics for those who grew S. aureus, Pseudomonas, or enteric organisms (compared with "no-growth" patients). CONCLUSION: Our results suggest that the application of mupirocin ointment appeared to minimize peritonitis of patients colonized with S. aureus. The use of mupirocin in this patient cohort has not led to mupirocin resistance. The increased peritonitis rate of patients who grew Pseudomonas or enteric organisms is of interest. We propose that greater attention to hygiene and catheter care in these patients is warranted. The increasing use of paid healthcare workers attending patients daily to help perform PD (assisted PD) gives an opportunity for us to address these wider issues.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteria/isolation & purification , Catheter-Related Infections/microbiology , Catheter-Related Infections/prevention & control , Catheters, Indwelling/microbiology , Equipment Contamination/prevention & control , Mupirocin/therapeutic use , Peritoneal Dialysis , Peritonitis/microbiology , Peritonitis/prevention & control , Bacteria/drug effects , Drug Resistance, Bacterial , Humans , Mupirocin/pharmacology , Ointments , Staphylococcus aureus/drug effects , Staphylococcus aureus/isolation & purification
9.
Trans R Soc Trop Med Hyg ; 113(4): 189-194, 2019 04 01.
Article in English | MEDLINE | ID: mdl-30597107

ABSTRACT

BACKGROUND: The association between diabetes and Strongyloides stercoralis remains controversial. We conducted a case-control study examining the association between diabetes and Strongyloides seropositivity in a large UK centre. METHODS: Between January 2013 and October 2016, cases and controls were identified by positive and negative Strongyloides serology, respectively. Demographic, clinical and microbiological data were retrospectively collected. Multivariate logistic regression analysis was performed. RESULTS: Over the study period, 532 samples were serologically tested for Strongyloides. After exclusion of duplicates and cases with missing data, 100 (22.3%; 95% CI 18.5-26.4%) out of 449 tested positive. Of seropositive cases, the mean age was 57 years (SD 16), 71 (71%) were male, 94 (94%) were migrants and 92 (92%) had eosinophilia.Univariate logistic regression analysis demonstrated a significant association between Strongyloides seropositivity and age (OR 1.04, 95% CI 1.02-1.05), male sex (OR 2.22, 95% CI 1.37-3.59), migration (OR 5.36, 95% CI 2.27-12.67), eosinophilia (OR 4.36, 95% CI 2.04-9.33) and diabetes (OR 3.52, 95% CI 2.19-5.66). In multivariate analysis, there remained a significant association between diabetes and Strongyloides seropositivity (OR 1.81, 95% CI 1.04-3.16). CONCLUSIONS: We demonstrated a high rate of Strongyloides seropositivity in our East London cohort and a significant association with diabetes.


Subject(s)
Antibodies, Helminth/blood , Diabetes Complications/parasitology , Seroepidemiologic Studies , Strongyloidiasis/blood , Strongyloidiasis/immunology , Adult , Aged , Aged, 80 and over , Case-Control Studies , Cohort Studies , Female , Humans , London/epidemiology , Male , Middle Aged , Multivariate Analysis , Prevalence , Retrospective Studies , Strongyloidiasis/epidemiology , Young Adult
10.
Int J Infect Dis ; 70: 104-106, 2018 May.
Article in English | MEDLINE | ID: mdl-29501836

ABSTRACT

We present a rare case of Shigella flexneri bacteraemia and toxic megacolon, and discuss the challenges of conventional laboratory techniques versus molecular PCR platforms in differentiating between Shigella species and Escherichia coli.


Subject(s)
Dysentery, Bacillary/diagnosis , Megacolon, Toxic/diagnosis , Adult , Clinical Laboratory Techniques , Dysentery, Bacillary/complications , Humans , Male , Megacolon, Toxic/etiology , Serogroup , Shigella flexneri/genetics
11.
Postgrad Med J ; 94(1110): 212-215, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29463684

ABSTRACT

BACKGROUND AND AIM: In 2017, National Health Service Improvement set a 10% reduction target for Escherichia coli bacteraemia by 2018, followed by a 50% reduction in healthcare-associated Gram-negative bacteraemias by 2022. We analysed consecutive cases of E. coli bacteraemia and devised a strategy to achieve these targets. METHODS: From December 2012 to November 2013, demographic, clinical and microbiological data were prospectively collected on all patients with bacteraemia at the Royal London Hospital in East London, UK. RESULTS: There were 594 significant bacteraemic episodes and 207 (34.8%) were E. coli. Twenty-four (11.6%) of the E. coli isolates were extended spectrum beta-lactamase producers, 22 (10.6%) gentamicin resistant and 2 (1.0%) amikacin resistant. The three most common sites of infection were pyelonephritis 105 (56.7%), catheter-associated urinary tract infection 22 (10.6%), and other medical devices and procedures that cause bacteraemia 32 (15.5%). In the pyelonephritis group, trimethoprim resistance in urinary isolates was 16/47 (34.0%) compared with 3/47 (6.4%) for nitrofurantoin. Twelve months postbacteraemia, recurrent bacteraemia rates were 10/105 (9.5%). There were 44 medical device-associated E. coli bacteraemias, and 22 (50%) were urinary catheter associated. There were 10 patients with E. coli bacteraemia caused by procedures, seven genitourinary or biliary tract instrumentation and three postgastrointestinal surgery. CONCLUSION: E. coli bacteraemias related to urosepsis could have been prevented by better empirical treatment and targeted prophylaxis. Urinary catheter quality improvement programmes should contribute to a further reduction. For patients undergoing high-risk urinary or biliary tract procedures or device manipulation, we advocate single-dose amikacin prophylaxis.


Subject(s)
Bacteremia/microbiology , Bacteremia/prevention & control , Cross Infection/microbiology , Cross Infection/prevention & control , Escherichia coli Infections/microbiology , Escherichia coli Infections/prevention & control , Hospitals, Teaching , Adolescent , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Biliary Tract Diseases/surgery , Catheter-Related Infections/microbiology , Catheter-Related Infections/prevention & control , Child , Child, Preschool , Drug Resistance, Multiple, Bacterial , Female , Health Services Research , Humans , London , Male , Middle Aged , Prospective Studies , Quality Improvement , Urinary Catheterization/adverse effects , Urinary Catheterization/standards , Urinary Catheters/microbiology , Urinary Tract Infections/microbiology , Urinary Tract Infections/prevention & control , Young Adult
12.
Postgrad Med J ; 93(1101): 382-388, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27821624

ABSTRACT

BACKGROUND: The clinical and cost-effectiveness of outpatient parenteral antimicrobial therapy (OPAT) services are well described. We used a blood culture database as a novel approach to case finding and determined its utility in identifying inpatients suitable for OPAT. METHODS: From December 2012 to November 2013, consecutive adult inpatients with bacteraemia, and those recruited to OPAT, were prospectively studied. Univariate and multivariate logistic regression analysis were used to investigate the association between bacteraemic patient characteristics and OPAT recruitment. RESULTS: There were 470 bacteraemic and 134 OPAT patients. The blood culture database identified 22 (16.4%; CI 10.5 to 23.6) additional patients suitable for OPAT, 4.7% (95% CI 3.0% to 7.0%) of the total bacteraemic cohort. 20 (90.9%) of these patients had community-acquired bacteraemia. Bacteraemic patients with urinary tract infections (UTIs), 11/157 (7.0%; 95% CI 3.5% to 12.2%) were most commonly recruited to OPAT and Escherichia coli was the most common blood culture isolate. In the E. coli bacteraemic subgroup, extended-spectrum ß-lactamase (ESBL) producers were significantly higher in the OPAT group, compared with the non-OPAT group, 9/11 (81.8%) vs 17/192 (8.9%), p<0.001. Among OPAT patients, there were no deaths within 30 days and no significant difference in relapse rates between bacteraemic and non-bacteraemic patients, 1/22 (4.6%) vs 5/112 (4.5%). In logistic regression analysis, there were no patient characteristics in the bacteraemic cohort that predicted recruitment to OPAT. In a subgroup analysis of patients with Gram-negative bacteraemia, ESBL production was strongly associated with OPAT recruitment, OR 5.85 (95% CI 1.94 to 17.58), p=0.002. CONCLUSIONS: A blood culture database proved a useful adjuvant to a clinical referral system, particularly for patients with community onset, multidrug resistant UTIs caused by ESBL producing E. coli. All bacteraemic patients recruited to OPAT received treatment safely and had good clinical outcomes.


Subject(s)
Ambulatory Care , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Blood Culture , Adolescent , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Databases, Factual , Female , Humans , Infusions, Parenteral , Male , Middle Aged , Prospective Studies , Referral and Consultation
13.
Infection ; 44(5): 617-22, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27138334

ABSTRACT

BACKGROUND: There is lack of outcome data for bacteraemic patients on specialist renal units. We described demographic, clinical, microbiological data and outcomes for bacteraemic adult renal transplant and non-transplant patients at a London Teaching Hospital. We also assessed the appropriateness of empirical antibiotic policy. METHODS: From December 2012 to November 2013, demographic, clinical and microbiological data were collected on consecutive patients with bacteraemia on a specialist UK renal unit. Empirical anti-microbial policy, based upon sites of infection, was piperacillin/tazobactam and amikacin, or meropenem for graft pyelonephritis, and vancomycin and gentamicin for suspected central venous catheter (CVC) associated infection. RESULTS: 113 bacteraemic episodes occurred in 83 patients. One patient had two bacteraemic episodes, one on haemodialysis and another after transplantation so appear in both groups. In the non-transplant group, 30-day mortality was 4/59 (6.8 %), more than the renal transplant group, 0/25 (0 %). While graft pyelonephritis was the predominant cause of bacteraemic episodes in renal transplant patients, 25/36 (69.4 %), there were a variety of other causes in the non-transplant group including uncomplicated line associated bacteraemia, 36/77 (46.8 %), complicated line associated bacteraemia, 11/77 (14.3 %) and bacteraemia unrelated to vascular access sites 19/77 (24.7 %). Overall, commonest isolates were Methicillin-sensitive Staphylococcus aureus 20/77 (26.3 %), and Escherichia coli 28/113 (24.8 %). There were no Methicillin-resistant Staphylococcus aureus isolates and, among Enterobacteriaceae, 15/57 (26.3 %) were extended spectrum beta-lactamase producers. CONCLUSIONS: Death only occurred in the non-transplant renal group. Empirical antibiotic treatment with either piperacillin/tazobactam and amikacin, or meropenem was appropriate for renal transplant recipients as most bacteraemic episodes were secondary to graft pyelonephritis. Vancomycin and gentamicin was appropriate empirical antibiotic treatment for non-transplant patients with CVC associated infections, but not optimal for other sites of infection.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Kidney Transplantation , Transplant Recipients , Adolescent , Adult , Aged , Aged, 80 and over , Bacteremia/microbiology , Bacteria/classification , Bacteria/isolation & purification , Female , Humans , Kidney Transplantation/statistics & numerical data , London , Male , Middle Aged , Transplant Recipients/statistics & numerical data , Treatment Outcome , Young Adult
14.
J Clin Microbiol ; 53(7): 2230-7, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25972414

ABSTRACT

The rapid identification of antimicrobial resistance is essential for effective treatment of highly resistant Mycobacterium tuberculosis. Whole-genome sequencing provides comprehensive data on resistance mutations and strain typing for monitoring transmission, but unlike for conventional molecular tests, this has previously been achievable only from cultures of M. tuberculosis. Here we describe a method utilizing biotinylated RNA baits designed specifically for M. tuberculosis DNA to capture full M. tuberculosis genomes directly from infected sputum samples, allowing whole-genome sequencing without the requirement of culture. This was carried out on 24 smear-positive sputum samples, collected from the United Kingdom and Lithuania where a matched culture sample was available, and 2 samples that had failed to grow in culture. M. tuberculosis sequencing data were obtained directly from all 24 smear-positive culture-positive sputa, of which 20 were of high quality (>20× depth and >90% of the genome covered). Results were compared with those of conventional molecular and culture-based methods, and high levels of concordance between phenotypical resistance and predicted resistance based on genotype were observed. High-quality sequence data were obtained from one smear-positive culture-negative case. This study demonstrated for the first time the successful and accurate sequencing of M. tuberculosis genomes directly from uncultured sputa. Identification of known resistance mutations within a week of sample receipt offers the prospect for personalized rather than empirical treatment of drug-resistant tuberculosis, including the use of antimicrobial-sparing regimens, leading to improved outcomes.


Subject(s)
Bacteriological Techniques/methods , Drug Resistance, Bacterial , Genotyping Techniques/methods , Mycobacterium tuberculosis/genetics , Specimen Handling/methods , Sputum/microbiology , Tuberculosis, Pulmonary/microbiology , Humans , Lithuania , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/isolation & purification , Sequence Analysis, DNA/methods , Time Factors , Tuberculosis, Pulmonary/diagnosis , United Kingdom
15.
Postgrad Med J ; 89(1052): 329-34, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23520064

ABSTRACT

PURPOSE: There is lack of contemporary outcome data on patients with hospital-acquired infections that cause bacteraemia. We determined the risk factors for 7-day mortality and investigated the hypothesis that, compared with central venous catheter (CVC)-associated bacteraemic infections, catheter-associated bacteraemic urinary tract infections (UTIs) were significantly associated with 7-day mortality. METHODS: From October 2007 to September 2008, demographical, clinical and microbiological data were collected on patients with hospital-acquired bacteraemia. Patients were followed until death, hospital discharge or recovery from infection. Risk factors for 7-day mortality were determined and multivariate logistic regression was used to define the association between catheter-associated bacteraemic UTIs and likelihood of death. RESULTS: 559 bacteraemic episodes occurred in 437 patients. Overall, there were 90 deaths (20.6%) at 7 days and 153 deaths (35.0%) at 30 days. Among patients with catheter-associated bacteraemic UTIs, 7-day and 30-day mortalities associated with each bacteraemic episode were 25/83 (30.1%) and 33/83 (39.8%), respectively. Within this subgroup, the commonest isolates were Escherichia coli, 36 (43.4%), Proteus mirabilis, 11 (13.3%) and Pseudomonas aeruginosa, 9 (10.8%). There were 22 (26.5%) multiple drug-resistant isolates and, of the E coli infections, 6 (16.7%) were extended spectrum ß-lactamase producers. In univariate analysis, the variables found to have the strongest association with 7-day mortality were age, Pitt score, Charlson comorbidity index (CCI), medical speciality and site of infection. Compared with CVC-associated bacteraemic infections, there was a significant association between catheter-associated bacteraemic UTIs and 7-day mortality (OR 4.16, 95% CI 1.86 to 9.33). After adjustment for age and CCI, this association remained significant (OR 2.90, 95% CI 1.19 to 7.07). CONCLUSIONS: Compared with CVC-associated bacteraemic infections, catheter-associated bacteraemic UTIs were significantly associated with 7-day mortality. Efforts to reduce these infections should be prioritised.


Subject(s)
Bacteremia/epidemiology , Catheter-Related Infections/epidemiology , Cross Infection/epidemiology , Urinary Tract Infections/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Bacteremia/microbiology , Bacteremia/mortality , Catheter-Related Infections/microbiology , Catheter-Related Infections/mortality , Child , Child, Preschool , Cross Infection/microbiology , Cross Infection/mortality , Drug Resistance, Bacterial , Drug Resistance, Multiple , Escherichia coli Infections/epidemiology , Female , Humans , Infant , Male , Middle Aged , Patient Outcome Assessment , Proteus Infections/epidemiology , Pseudomonas Infections/epidemiology , Risk Factors , Survival Analysis , United Kingdom/epidemiology , Urinary Tract Infections/microbiology , Urinary Tract Infections/mortality
18.
Postgrad Med J ; 87(1033): 757-62, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21798969

ABSTRACT

PURPOSE: Within the UK, there is lack of contemporary data on clinical outcomes in patients admitted to hospital with severe community acquired infection. The purpose of this study was to determine outcomes and risk factors associated with mortality in consecutive patients admitted to a UK NHS trust with community acquired infections that cause bacteraemia. METHODS: From September 2007 to August 2008, demographic, clinical and microbiological data were collected on patients with laboratory confirmed bacteraemia. Multivariate logistic regression was used to determine the association between predicted variables and likelihood of death. RESULTS: 686 bacteraemic episodes occurred in 681 patients. The most common sites of infection were non-catheter associated urinary tract infections (140, 20.4%) and biliary tract infections (62, 9.1%). The most common organisms were Escherichia coli (238, 34.7%), Staphylococcus aureus (84, 12.2%) and Streptococcus pneumoniae (40, 5.8%). Of the E coli infections, extended spectrum ß-lactamase (ESBL) producers accounted for 21/238 (8.8%), and of the S aureus infections, methicillin resistant S aureus (MRSA) accounted for 14/84 (16.7%). 124 (18.2%, 95% CI 15.3% to 21.1%) people died within 7 days and 170 (25.0%, 95% CI 21.7% to 28.2%) within 30 days. Age (OR 2.17, 95% CI 1.54 to 3.06), Charlson comorbidity index (OR 1.21, 95% CI 1.10 to 1.34), and Pitt score (OR 1.49, 95% CI 1.32 to 1.67) were highly significantly associated with 30 day mortality (p<0.001). Delay in appropriate antibiotic treatment (OR 1.35, 95% CI 1.05 to 1.75) and an undefined site of infection (OR 2.05, 95% CI 1.19 to 3.53) were less significantly associated with 30 day mortality (p<0.05). CONCLUSION: The 30 day mortality rate in consecutive patients with community acquired bacteraemic infection was 25.0%. These figures could be used as performance indicators to compare outcomes in different UK NHS trusts. With the exception of delay in appropriate antibiotic treatment, predictors of mortality at 30 days were non-modifiable.


Subject(s)
Bacteremia/mortality , Clostridium Infections/mortality , Community-Acquired Infections/mortality , Equipment and Supplies, Hospital/microbiology , Escherichia coli Infections/mortality , Staphylococcal Infections/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Child , Child, Preschool , Clostridioides difficile/isolation & purification , Clostridium Infections/drug therapy , Community-Acquired Infections/drug therapy , Community-Acquired Infections/microbiology , Cross Infection/drug therapy , Cross Infection/transmission , Equipment Contamination , Escherichia coli/isolation & purification , Escherichia coli Infections/drug therapy , Female , Hospitals , Humans , Infant , Male , Methicillin Resistance , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Middle Aged , Multivariate Analysis , Risk Factors , Staphylococcal Infections/drug therapy , United Kingdom/epidemiology , Young Adult
20.
Int J Infect Dis ; 14(8): e717-22, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20542460

ABSTRACT

OBJECTIVES: To determine the utility of 'risk assessment' in selecting Mycobacterium tuberculosis isolates for rifampin resistance or rpoB genotyping compared to 'non-selectively' genotyping all isolates. Secondly, we examined the association between past treatment and drug resistance. METHODS: From January 2003 to December 2006, demographic, clinical, and laboratory data were prospectively collected on patients with laboratory-confirmed tuberculosis (TB). On the basis of past treatment for active TB infection or known exposure to drug-resistant TB, selected samples were sent to a mycobacterial reference laboratory for rpoB genotyping. A multivariable logistic regression model was developed to examine the association between past treatment and drug resistance, adjusted for other factors. Sensitivity, specificity, and negative and positive predictive values of past treatment as a predictor for drug resistance were determined. RESULTS: There were 392 patient episodes of culture-proven TB. Thirty-three drug-resistant isolates were cultured from 30 patients: 29 (87.9%) were isoniazid-resistant, three (9.1%) were multidrug-resistant (MDR), and one (3.0%) was rifampin mono-resistant. One patient with isoniazid resistance developed recurrent disease, and two isolates, initially isoniazid-resistant, mutated and became MDR TB. Based on risk assessment, rpoB genotyping was performed on 19 samples, and two (10.5%) had mutations that predicted multiple drug resistance. Although for MDR TB, a past history of treatment predicted two out of three patients with acquired resistance, adjusted analysis did not demonstrate a significant association between previous treatment of active TB and drug resistance (odds ratio 1.5, 95% confidence interval (CI) 0.4-5.6). The positive predictive value of past treatment as a predictor for drug resistance was 12.0% (95% CI 2.6-31.2%). CONCLUSION: Although numbers of MDR TB were too small to draw meaningful conclusions, past treatment may be useful in selecting samples for rpoB genotyping. Overall, previous treatment had a low positive predictive value for drug resistance in an area bordering East London.


Subject(s)
Antitubercular Agents/therapeutic use , Drug Resistance, Bacterial , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antitubercular Agents/pharmacology , Bacterial Proteins/genetics , Child , Child, Preschool , DNA-Directed RNA Polymerases , Female , Humans , Infant , Infant, Newborn , Logistic Models , London , Male , Microbial Sensitivity Tests/methods , Models, Biological , Mycobacterium tuberculosis/classification , Mycobacterium tuberculosis/genetics , Predictive Value of Tests , Rifampin/pharmacology , Rifampin/therapeutic use , Sensitivity and Specificity , Tuberculosis/diagnosis , Tuberculosis/microbiology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology , Young Adult
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