Sally Roberts

Treatment Outcomes for Serious Infections Caused by Methicillin-Resistant Staphylococcus aureus with Reduced Vancomycin Susceptibility

Although infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility (SA-RVS) have been reported from a number of countries, including Australia, the optimal therapy is unknown. We reviewed the clinical features, therapy, and outcome of 25 patients with serious infections due to SA-RVS in Australia and New Zealand. Eight patients had endocarditis, 9 had bacteremia associated with deep-seated infection, 6 had osteomyelitis or septic arthritis, and 2 had empyema. All patients had received vancomycin before the isolation of SA-RVS, and glycopeptide treatment had failed for 19 patients (76%). Twenty-one patients subsequently received active treatment, which was effective for 16 patients (76%). Eighteen patients received linezolid, which was effective in 14 (78%), including 4 patients with endocarditis. Twelve patients received a combination of rifampicin and fusidic acid. Surgical intervention was required for 15 patients (60%). Antibiotic therapy, especially linezolid with or without rifampicin and fusidic acid, in conjunction with surgical debulking is effective therapy for the majority of patients with serious infections (including endocarditis) caused by SA-RVS.

Infection of Orthopedic Prostheses after Staphylococcus aureus Bacteremia

We prospectively evaluated 53 patients with prosthetic joints and 27 patients with other orthopedic prosthetic devices who developed Staphylococcus aureus bacteremia (SAB). After exclusion of patients with primary postoperative infections, the risk of a prosthesis becoming infected by means of hematogenous seeding after SAB was 34% (15 of 44 patients) for prosthetic joints and 7% (1 of 15 patients) for other orthopedic prostheses.

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.

Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia.

ABSTRACT A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ≥400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a “real-world” context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively; P < 0.001). Obtaining the recommended vancomycin target AUC/MIC of ≥400 using BMD was not associated with lower 30-day all-cause or attributable mortality from SAB (P = 0.132 and P = 0.273, respectively). However, an alternative vancomycin AUC/MIC of >373, derived using classification and regression tree analysis, was associated with reduced mortality (P = 0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ≥400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods.

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.

Comparative in vitro activity of carbapenems against major Gram-negative pathogens: results of Asia-Pacific surveillance from the COMPACT II study.

Resistance rates amongst Gram-negative pathogens are increasing in the Asia-Pacific region. The Comparative Activity of Carbapenem Testing (COMPACT) II study surveyed the carbapenem susceptibility and minimum inhibitory concentrations (MICs) of doripenem, imipenem and meropenem against 1260 major Gram-negative pathogens isolated from hospitalised patients at 20 centres in five Asia-Pacific countries (New Zealand, the Philippines, Singapore, Thailand and Vietnam) during 2010. Pseudomonas aeruginosa (n=625), Enterobacteriaceae (n=500), and other Gram-negative pathogens including Acinetobacter baumannii (n=135) were collected from patients with bloodstream infection (32.2%), nosocomial pneumonia including ventilator-associated pneumonia (58.1%), and complicated intra-abdominal infection (9.7%), with 36.7% being isolated from patients in an Intensive Care Unit. As high as 29.8% of P. aeruginosa and 73.0% of A. baumannii isolates were not susceptible to at least a carbapenem, whereas the majority of Enterobacteriaceae (97.2%) were susceptible to all carbapenems. Respective MIC(50)/MIC(90) values (MICs for 50% and 90% of the organisms, respectively) of doripenem, imipenem and meropenem were: 0.38/8, 1.5/32 and 0.38/16 mg/L for P. aeruginosa; 0.023/0.094, 0.25/0.5 and 0.032/0.094 mg/L for Enterobacteriaceae; and 32/64, 32/128 and 32/64 mg/L for A. baumannii. Doripenem and meropenem had comparable activity against P. aeruginosa, both being more active than imipenem. All carbapenems were highly potent against Enterobacteriaceae, although imipenem demonstrated higher MIC values than doripenem and meropenem. The three carbapenems showed less activity against A. baumannii. The high prevalence of carbapenem resistance amongst important nosocomial pathogens (P. aeruginosa and A. baumannii) warrants rigorous infection control measures and appropriate antimicrobial use in the Asia-Pacific region.

Haemophilus ducreyi Causing Chronic Skin Ulceration in Children Visiting Samoa

Chancroid is a sexually transmitted infection associated with genital ulceration and lymphadenopathy caused by Haemophilus ducreyi. Localized skin infections, in the absence of genital lesions, have not been previously reported. We report 3 cases of lower limb ulceration in children caused by H. ducreyi and postulate that H. ducreyi may be a previously unrecognized cause of chronic skin ulceration.

Cannabis, Ischemic Stroke, and Transient Ischemic Attack A Case-Control Study

Background and Purpose— There is a temporal relationship between cannabis use and stroke in case series and population-based studies. Methods— Consecutive stroke patients, aged 18 to 55 years, who had urine screens for cannabis were compared with a cohort of control patients admitted to hospital without cardiovascular or neurological diagnoses. Results— One hundred sixty of 218 (73%) ischemic stroke/transient ischemic attack patients had urine drug screens (100 men; mean [SD] age, 44.8 [8.7] years). Twenty-five (15.6%) patients had positive cannabis drug screens. These patients were more likely to be men (84% versus 59%; &khgr;2: P=0.016) and tobacco smokers (88% versus 28%; &khgr;2: P<0.001). Control urine samples were obtained from 160 patients matched for age, sex, and ethnicity. Thirteen (8.1%) control participants tested positive for cannabis. In a logistic regression analysis adjusted for age, sex, and ethnicity, cannabis use was associated with increased risk of ischemic stroke/transient ischemic attack (odds ratio, 2.30; 95% confidence interval, 1.08–5.08). However after adjusting for tobacco use, an association independent of tobacco could not be confirmed (odds ratio, 1.59; 95% confidence interval, 0.71–3.70). Conclusions— This study provides evidence of an association between a cannabis lifestyle that includes tobacco and ischemic stroke. Further research is required to clarify whether there is an association between cannabis and stroke independent of tobacco. Clinical Trial Registration— URL: http://www.anzctr.org.au. Unique identifier: ACTRN12610000198022

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.

Efficacy of antibiotic-impregnated external ventricular drain catheters

We prospectively compared the incidence of ventriculitis associated with external ventricular drains (EVD) impregnated with clindamycin and rifampicin with historical controls. We found the use of antibiotic impregnated (AI) EVDs showed a significant decrease in positive cerebrospinal fluid cultures and a significant delay in time to EVD infection.