Deborah A. Williamson

Escherichia coli Bloodstream Infection After Transrectal Ultrasound–Guided Prostate Biopsy: Implications of Fluoroquinolone-Resistant Sequence Type 131 as a Major Causative Pathogen

BACKGROUND Transrectal ultrasound-guided (TRUS) prostate biopsy is a commonly performed procedure, and fluoroquinolones are the most frequently given prophylactic antimicrobials. In the context of increasing fluoroquinolone resistance, and the international emergence of fluoroquinolone-resistant sequence type 131 (ST131) Escherichia coli, we describe a large series of E. coli bacteremia after TRUS biopsy. METHODS All male patients admitted with community-onset (CO) E. coli bacteremia from January 2006 through December 2010 were included. Patient characteristics, treatment outcomes, and rates of antimicrobial resistance were compared between patients with TRUS biopsy-related bacteremia and other male patients with CO E. coli bacteremia. Molecular typing was performed on E. coli isolates to determine phylogenetic group. RESULTS A total of 258 male patients were admitted with CO E. coli bacteremia. Of these, 47 patients (18%) were admitted after TRUS biopsy. Patients who had undergone TRUS biopsy were twice as likely to require intensive care admission (25% vs 12%) and had significantly higher rates of resistance to gentamicin (43%), trimethoprim-sulphamethoxazole (60%), and ciprofloxacin (62%) as well as all 3 agents in combination (19%). Thirty-six percent of post-TRUS biopsy patients did not receive active empirical antibiotic therapy. The ST131 clone accounted for 41% of all E. coli isolates after TRUS biopsy. CONCLUSIONS E. coli bacteremia can be a life-threatening complication of TRUS biopsy. Infecting strains are frequently multidrug-resistant and resistant to common empirical antibiotic agents. E. coli ST131 is an important cause of sepsis after TRUS biopsy. Further studies should evaluate colonization with fluoroquinolone-resistant E. coli as a risk factor for postbiopsy sepsis.

The emerging threat of multidrug-resistant Gram-negative bacteria in urology

Antibiotic resistance in Gram-negative uropathogens is a major global concern. Worldwide, the prevalence of Enterobacteriaceae that produce extended-spectrum β-lactamase or carbapenemase enzymes continues to increase at alarming rates. Likewise, resistance to other antimicrobial agents including aminoglycosides, sulphonamides and fluoroquinolones is also escalating rapidly. Bacterial resistance has major implications for urological practice, particularly in relation to catheter-associated urinary tract infections (UTIs) and infectious complications following transrectal-ultrasonography-guided biopsy of the prostate or urological surgery. Although some new drugs with activity against Gram-negative bacteria with highly resistant phenotypes will become available in the near future, the existence of a single agent with activity against the great diversity of resistance is unlikely. Responding to the challenges of Gram-negative resistance will require a multifaceted approach including considered use of current antimicrobial agents, improved diagnostics (including the rapid detection of resistance) and surveillance, better adherence to basic measures of infection prevention, development of new antibiotics and research into non-antibiotic treatment and preventive strategies.

Infectious Complications Following Transrectal Ultrasound–Guided Prostate Biopsy: New Challenges in the Era of Multidrug-Resistant Escherichia coli

Transrectal ultrasound (TRUS)-guided prostate biopsy is currently considered the standard technique for obtaining tissue to make a histological diagnosis of prostatic carcinoma. Infectious complications following TRUS-guided prostate biopsy are well described, and are reportedly increasing in incidence. The role of antibiotic prophylaxis in reducing post-TRUS biopsy infections is now established, and many guidelines suggest that fluoroquinolone antimicrobials are the prophylactic agents of choice. Of note, however, recent reports suggest an emerging association between TRUS biopsy and subsequent infection with fluoroquinolone-resistant Escherichia coli. Against this background, we provide an overview of the epidemiology, prevention, and treatment of infectious complications following TRUS biopsy, in the wider context of increasing global antimicrobial resistance.

Identification and molecular characterisation of New Delhi metallo-β-lactamase-1 (NDM-1)- and NDM-6-producing Enterobacteriaceae from New Zealand hospitals

The global spread of New Delhi metallo-β-lactamase (NDM) is of significant public health concern. This study sought to determine whether bla(NDM) was present in Enterobacteriaceae isolates displaying resistance to carbapenems that were submitted to the National Antibiotic Reference Laboratory, Institute of Environmental Science and Research (Porirua, New Zealand) during 2009 and 2010. Isolates were tested for the presence of β-lactamase genes and 16S rRNA methylase genes by polymerase chain reaction (PCR) and sequencing. Plasmid transfer studies were undertaken on isolates found to be harbouring bla(NDM). Molecular typing was performed by multilocus sequence typing (MLST). The bla(NDM-1) gene was identified in four Enterobacteriaceae isolates (two Escherichia coli, one Klebsiella pneumoniae and one Proteus mirabilis) from four patients in New Zealand hospitals in 2009 and 2010. In addition, the bla(NDM-6) gene, which differed from bla(NDM-1) by a point mutation at position 698 (C→T), was also identified in an E. coli isolate from the same patient who harboured the bla(NDM-1)-positive P. mirabilis. All four patients had recently been hospitalised or received health care in India. Four of the isolates also produced a CTX-M-15 extended-spectrum β-lactamase and/or plasmid-mediated AmpC β-lactamase, and all five isolates harboured the plasmid-mediated 16S rRNA methylase rmtC gene. The E. coli types were diverse by MLST, and the K. pneumoniae isolate belonged to the internationally disseminated sequence type 11 (ST11) clone. These findings further illustrate the diversity of phenotypic and genotypic features found in association with bla(NDM), in addition to documenting the international spread of this resistance mechanism, notably into a country with historically low rates of antimicrobial resistance.

Clinical failures associated with rpoB mutations in phenotypically occult multidrug-resistant Mycobacterium tuberculosis.

SETTING Recently, Mycobacterium tuberculosis isolates have been described that test phenotypically susceptible to rifampicin (RMP) yet harbour genotypic rpoB mutations. OBJECTIVE 1) To investigate the impact of such mutations on clinical outcomes among RMP-susceptible isolates, and 2) to determine the prevalence of rpoB mutations among isoniazid (INH) monoresistant isolates at our laboratory and to describe the association between the presence of these mutations and clinical outcomes. METHODS M. tuberculosis isolates were screened for mutations in the rpoB gene using the Cepheid Gene-Xpert® MTB/RIF assay. Clinical correlation was made by reviewing patient case notes. RESULTS Isolates from 94 patients were found to have INH-resistant, RMP-susceptible profiles. Clinical information was available for 52 patients, including three whose isolates had rpoB mutations. All three of these patients had treatment failures, compared to two of 49 patients whose isolates did not have rpoB mutations (P = 0.0005). DISCUSSION We demonstrate a significant association between the presence of rpoB gene mutations that are not detected at the current RMP critical concentration and treatment failure. We suggest that a review of the current RMP critical concentration is warranted to ensure that RMP is not used inappropriately for the treatment of phenotypically occult multidrug-resistant tuberculosis.

Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke

Treatment with CD34+ hematopoietic stem/progenitor cells has been shown to improve functional recovery in nonhuman models of ischemic stroke via promotion of angiogenesis and neurogenesis. We aimed to determine the safety and feasibility of treatment with CD34+ cells delivered intra‐arterially in patients with acute ischemic stroke. This was the first study in human subjects. We performed a prospective, nonrandomized, open‐label, phase I study of autologous, immunoselected CD34+ stem/progenitor cell therapy in patients presenting within 7 days of onset with severe anterior circulation ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≥8). CD34+ cells were collected from the bone marrow of the subjects before being delivered by catheter angiography into the ipsilesional middle cerebral artery. Eighty‐two patients with severe anterior circulation ischemic stroke were screened, of whom five proceeded to treatment. The common reasons for exclusion were age >80 years (n = 19); medical instability (n = 17), and significant carotid stenosis (n = 13). The procedure was well tolerated in all patients, and no significant treatment‐related adverse effects occurred. All patients showed improvements in clinical functional scores (Modified Rankin Score and NIHSS score) and reductions in lesion volume during a 6‐month follow‐up period. Autologous CD34+ selected stem/progenitor cell therapy delivered intra‐arterially into the infarct territory can be achieved safely in patients with acute ischemic stroke. Future studies that address eligibility criteria, dosage, delivery site, and timing and that use surrogate imaging markers of outcome are desirable before larger scale clinical trials.

Baseline prevalence of antimicrobial resistance and subsequent infection following prostate biopsy using empirical or altered prophylaxis: A bias-adjusted meta-analysis

Transrectal ultrasound-guided prostate biopsy (TRUSPB) is a commonly performed urological procedure. Recent studies suggest that pre-biopsy screening for fluoroquinolone-resistant (FQ-R) pathogens may be useful in reducing post-biopsy infections. We sought to determine the baseline prevalence of fluoroquinolone (FQ) resistance in rectal flora and to investigate the relationship between pre-biopsy carriage of FQ-R pathogens and the risk of post-TRUSPB infection. Electronic databases were searched for related literature. Studies were assessed for methodological quality and comparable outcomes prior to meta-analysis (using quality- and random-effects models). Nine studies, representing 2541 patients, were included. The prevalence of FQ resistance was higher (20.4%, 95% CI 18.2-22.6%) in rectal cultures obtained following FQ-based prophylaxis compared with those obtained before (12.8%, 95% CI 10.7-15.0%). Overall infection rates in patients using empirical prophylaxis were higher (3.3%, 95% CI 2.6-4.2%) than in those using altered (targeted/protocol) regimens (0.3%, 95% CI 0-0.9%). Higher infection rates were seen in men with FQ-R rectal cultures (7.1%, 95% CI 4.0-10.5%) than in those with FQ-sensitive (FQ-S) rectal cultures (1.1%, 95% CI 0.5-1.8%). For every 14 men with FQ-R rectal cultures, one additional infection was observed compared with men with FQ-S rectal cultures. Prior FQ use and prior genitourinary infection were significant risk factors for FQ-R colonisation. FQ resistance in rectal flora is a significant predictor of post-TRUSPB infection and may require re-assessment of empirical antimicrobial prophylaxis methods. Altered prophylaxis based on rectal culturing prior to TRUSPB may reduce morbidity and potentially provide economic benefits to health services.

An evaluation of the Xpert MTB/RIF assay and detection of false-positive rifampicin resistance in Mycobacterium tuberculosis.

Recent reports suggest that false-positive rifampicin resistance may be assigned by the Xpert MTB/RIF assay. We analysed 169 specimens using the MTB/RIF assay. Using culture as the gold standard, we found that the assay had 100% sensitivity and specificity for detecting M. tuberculosis. However, we found that the assay incorrectly assigned rifampicin resistance in 4/13 (31%) of cases.

The potential benefit of stem cell therapy after stroke: an update

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Human stem cell therapy in ischaemic stroke: a review

Stroke is a leading cause of death and disability. Globally, 15 million people suffer a stroke each year, of whom more than 5 million die, and a further 5 million are left permanently disabled. Current treatment options offer modest benefits, and there is a pressing need for new and effective treatments. Stem cell therapy is a well-established treatment modality for various haematological diseases, with its use now being explored in different disease processes, including various neurological diseases, as well as vascular conditions such as ischaemic heart disease and peripheral vascular disease. Promising results have been seen in animal models of stroke, with evidence of significant functional benefits. Translation to the bedside, however, is in its early stages. This review will discuss the scientific background to stem cell therapy in ischaemic stroke, including evidence from current clinical trials.