Iain B. Gosbell

Predictors of Mortality in Staphylococcus aureus Bacteremia

SUMMARY Staphylococcus aureus bacteremia (SAB) is an important infection with an incidence rate ranging from 20 to 50 cases/100,000 population per year. Between 10% and 30% of these patients will die from SAB. Comparatively, this accounts for a greater number of deaths than for AIDS, tuberculosis, and viral hepatitis combined. Multiple factors influence outcomes for SAB patients. The most consistent predictor of mortality is age, with older patients being twice as likely to die. Except for the presence of comorbidities, the impacts of other host factors, including gender, ethnicity, socioeconomic status, and immune status, are unclear. Pathogen-host interactions, especially the presence of shock and the source of SAB, are strong predictors of outcomes. Although antibiotic resistance may be associated with increased mortality, questions remain as to whether this reflects pathogen-specific factors or poorer responses to antibiotic therapy, namely, vancomycin. Optimal management relies on starting appropriate antibiotics in a timely fashion, resulting in improved outcomes for certain patient subgroups. The roles of surgery and infectious disease consultations require further study. Although the rate of mortality from SAB is declining, it remains high. Future international collaborative studies are required to tease out the relative contributions of various factors to mortality, which would enable the optimization of SAB management and patient outcomes.

Utility of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry following Introduction for Routine Laboratory Bacterial Identification

ABSTRACT Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) was evaluated prospectively in a diagnostic laboratory. Nine hundred twenty-seven organisms were tested in triplicate; 2,351/2,781 (85%) species and 2,681/2,781 (96%) genus identifications were correct. Known issues such as the misidentification of alpha-hemolytic streptococci as Streptococcus pneumoniae were easily corrected. Identifications cost AUD

Emergence of daptomycin resistance following vancomycin-unresponsive Staphylococcus aureus bacteraemia in a daptomycin-naïve patient—a review of the literature

0.45 per isolate and were available in minutes. MALDI-TOF MS is rapid, accurate, and inexpensive.

Staphylococcus aureus bacteremia, Australia.

A patient developed a daptomycin-resistant methicillin-resistant Staphylococcus aureus (MRSA) infection, despite being daptomycin-naïve, in the setting of persistent bacteraemia secondary to vertebral osteomyelitis. Modified population analysis profiling of sequential MRSA blood culture isolates revealed transition from a vancomycin-susceptible phenotype to a vancomycin-intermediate S. aureus (VISA) phenotype through a vancomycin-heteroresistant S. aureus (hVISA) intermediary. Increased cell wall thickening, determined by transmission electron microscopy, correlated with the emergence of daptomycin resistance. This case supports the current hypothesis that MRSA with reduced glycopeptide susceptibility are less susceptible to daptomycin because of a thickened cell wall. This may have significance for the use of daptomycin in salvage therapy. Other predictors of daptomycin resistance include bacteraemic persistence and the presence of high inoculum infections. As resistance may appear de novo and be unstable in vivo, all isolates should have daptomycin susceptibility testing performed. The optimal antibiotic option for salvage therapy of these daptomycin-resistant infections is unknown. However, these findings emphasise the importance of optimising management, including the consideration of early surgical intervention to avoid the emergence of daptomycin resistance, especially in high inoculum infections.

Cure of orthopaedic infection with Scedosporium prolificans, using voriconazole plus terbinafine, without the need for radical surgery

S. aureus bacteremia in Australia is increasingly caused by MRSA, which is likely to affect empiric prescribing of antimicrobial drugs in suspected cases.

Antimicrobial resistance in Staphylococcus aureus in Australian teaching hospitals, 1989-1999.

Summary Scedosporium prolificans infections of normal hosts usually require extensive debridement and sometimes amputation to effect cure, due to the intrinsic resistance of this species to available antifungal agents. Newer agents have not tested favourably. Variable results are obtained with voriconazole, and 100% resistance is described with echinocandins. Itraconazole and terbinafine has offered synergy against various moulds including S. prolificans. In vivo success is reported with the azole/terbinafine combination in S. apiospermum pulmonary infection and Pythium insidiosum periorbital cellulitis. We report a case of orthopaedic infection in a non‐immunocompromised host with S. prolificans, in which the combinations of itraconazole/terbinafine and voriconazole/terbinafine showed synergy in vitro, and success was achieved without radical surgery, using voriconazole and terbinafine.

Presence of biofilm containing viable multiresistant organisms despite terminal cleaning on clinical surfaces in an intensive care unit

An annual survey of antimicrobial resistance in clinical isolates of Staphylococcus aureus was conducted in 21 Australian teaching hospital microbiology laboratories in eight major cities from 1989 to 1999. A total of 19,000 isolates were tested for susceptibility to 18 antimicrobials, with 3795 being methicillin-resistant (MRSA). Resistance to ciprofloxacin in MRSA increased from 4.9% to 75.9%. The proportion of MRSA resistant to erythromycin decreased significantly (99.0%-88.9%), as did that to trimethoprim (98.4%-82.4%) and to tetracycline (96.5%-80.1%). The proportion of MRSA isolated increased in Sydney, Melbourne, Canberra, Adelaide, Perth, and Darwin, but not in Brisbane. The proportion in Hobart peaked in 1994. MRSA in Perth were predominantly non-multiresistant (nmMRSA) throughout the survey (i.e., resistant to less than three of eight indicator antibiotics) due mainly to local strains that originated in the community. The proportion of nmMRSA increased to modest levels in the other cities. In eastern cities, this was due to the appearance of strains closely related to nmMRSA seen in other countries of the southwestern Pacific.

Vancomycin Heteroresistance is Associated with Reduced Mortality in ST239 Methicillin-Resistant Staphylococcus aureus Blood Stream Infections

BACKGROUND Despite recent attention to surface cleaning and hand hygiene programmes, multiresistant organisms (MROs) continue to be isolated from the hospital environment. Biofilms, consisting of bacteria embedded in exopolymeric substances (EPS) are difficult to remove due to their increased resistance to detergents and disinfectants, and periodically release free-swimming planktonic bacteria back into the environment which may may act as an infection source. AIM To establish whether reservoirs of MROs exist in the environment as biofilms. METHODS Following terminal cleaning, equipment and furnishings were removed aseptically from an intensive care unit (ICU) and subjected to culture and scanning electron microscopy (SEM). Samples were placed in 5 mL of tryptone soya broth, sonicated for 5 min before plate culture on horse blood agar, Brillance MRSA and Brilliance VRE agar plates. Samples for SEM were fixed in 3% glutaraldehyde and hexamethyldisilizane (HMDS) prior to sputter-coating with gold and examination in an electron microscope. FINDINGS Biofilm was demonstrated visually on the sterile supply bucket, the opaque plastic door, the venetian blind cord, and the sink rubber, whereas EPS alone was seen on the curtain. Viable bacteria were grown from three samples, including MRSA from the venetian blind cord and the curtain. CONCLUSION Biofilm containing MROs persist on clinical surfaces from an ICU despite terminal cleaning, suggesting that current cleaning practices are inadequate to control biofilm development. The presence of MROs being protected within these biofilms may be the mechanism by which MROs persist within the hospital environment.

Methicillin-resistant Staphylococcus aureus vancomycin susceptibility testing: methodology correlations, temporal trends and clonal patterns

Background Despite hVISA infections being associated with vancomycin treatment failure, no previous study has been able to detect a mortality difference between heteroresistant vancomycin intermediate Staphylococcus aureus (hVISA) and vancomycin susceptible Staphylococcus aureus (VSSA) bloodstream infections (BSI). Methodology Consecutive methicillin-resistant S. aureus (MRSA) BSI episodes between 1996 and 2008 were reviewed. Patient demographics, clinical presentation, treatment and overall mortality at 30 days were extracted from the medical records. All isolates underwent vancomycin minimum inhibitory concentration (VMIC) testing by broth microdilution and Etest. hVISA was confirmed by population analysis profiling using the area under the curve method (PAP-AUC). Principal Findings 401 evaluable MRSA BSI episodes were identified over the 12 years. Of these, 46 (11.5%) and 2 (0.5%) were confirmed as hVISA and VISA by PAP-AUC respectively. hVISA predominantly occurred in ST239-like MRSA isolates with high VMIC (2 mg/L). Compared to VSSA, hVISA was associated with chronic renal failure (p<0.001), device related infections (haemodialysis access) (p<0.001) and previous vancomycin usage (p = 0.004). On multivariate analysis, independent predictors of mortality included age, presence of multiple co-morbidities, principal diagnosis, transit to ICU and severity of illness while infection related surgery and hVISA phenotype were associated with increased survival. Conclusions/Significance The presence of hVISA is dependent on the appropriate interplay between host and pathogen factors. hVISA in ST239 MRSA is an independent predictor of survival. Whether these findings would be replicated across all MRSA clones is unknown and warrants further study.

Whole genome sequence analysis of the first Australian OXA-48-producing outbreak-associated Klebsiella pneumoniae isolates : the resistome and in vivo evolution

OBJECTIVES To determine the correlation between various vancomycin MIC testing methodologies and explore the phenomenon of MIC creep. METHODS A total of 417 consecutive non-duplicate methicillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates from Liverpool Hospital between 1997 and 2008 were retrieved. All isolates were classified using PFGE and underwent susceptibility testing for vancomycin using a standard Etest (AB bioMérieux, Solna, Sweden), Vitek2(®) (AST-P612; bioMérieux, Inc., Durham, NC, USA) and broth microdilution (BMD) performed as per the CLSI method. RESULTS Over the 12 years, 78% (n = 326) of the isolates were multiresistant MRSA (ST239-like by PFGE, where ST stands for sequence type). The correlation between MIC testing methods was moderate with Spearmans correlation coefficients of 0.50 for BMD versus Etest (P < 0.001), 0.33 for BMD versus Vitek2(®) (P < 0.001) and 0.42 for Etest versus Vitek2(®) (P < 0.001). In general, Etest results were 1 dilution higher while the Vitek2(®) results were 1 dilution lower than the BMD MIC result. MIC creep was dependent on the MIC testing method and the measurement used for analysis (geometric mean MIC versus modal MIC versus frequency analysis), with creep detected for Etest regression analysis only. In contrast, the proportion of isolates with a BMD MIC ≥2 mg/L decreased from 16% to 9% in the latter half of the study. Modal MIC was stable over the 12 years at 1 mg/L irrespective of MIC method used. CONCLUSIONS Correlation between vancomycin MIC methodologies remains suboptimal. Temporal MIC trends should be interpreted with caution as these are dependent on the testing methodology and the measurement used for analysis.