Thomas Gottlieb

Control of fluoroquinolone resistance through successful regulation, Australia.

Restricted Fluoroquinolone use in humans and food animals has result in low rates of resistance in human pathogens

Staphylococcus aureus bacteremia, Australia.

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

Trimethoprim-induced aseptic meningitis and uveitis

We wish to report a case of trimethoprim-related uveitis and aseptic meningitis confirmed by rechallenge. An 18-year-old woman presented with a recent history of recurrent urinary tract infections. The first infection, 5 months previously, was treated with a 7-day course of trimethoprim. She made an uneventful recovery. 2 months later a recurrent urinary tract infection was diagnosed and trimethoprim was again prescribed. Within hours of the first dose of trimethoprim, she described the onset of headache, red and sore eyes, and neck ache. She was reviewed in the emergency department and her therapy was changed to co-amoxyclav. She completed a 7-day course. Her eye pain endured for 2 weeks. A subsequent urinary tract infection, 1 month later, was again treated with co-amoxyclav and she made an uncomplicated recovery. 2 months later she presented to the emergency department with headache, fever, painful red eyes, and photophobia. Earlier in the day she had attended her local medical officer, with a recurrence of urinary tract symptoms. A clinical diagnosis of cystitis was made and she was prescribed trimethoprim. She took her first dose about 4 h before her hospital presentation. On examination, she appeared unwell but was orientated and responsive. Her temperature was 37·5oC. Neck stiffness and a positive Kernig’s sign were both elicited and slit-lamp examination of both eyes revealed white cells in the anterior chamber and a proteinaceous “flare”, consistent with a bilateral anterior uveitis. Small non-tender anterior and posterior cervical lymph nodes were palpable. Her large joints were tender on passive movement. Investigations revealed an ESR of 22, a normal full blood count, white cell count, electrolytes, urea, creatinine, and liver function tests. Urine microscopy showed 11 to 100 10 white cells. Urine cultures yielded a mixed growth. A high vaginal swab showed no growth. For Chlamydia trachomatis, direct fluorescence on a cervical swab and C trachomatis urinary PCR were negative. Cerebrospinal fluid (CSF) microscopy showed 1 red cell, 3 polymorphonuclear cells, and 2 monocytes 10/L. The CSF was sterile. The CSF protein was elevated at 0·66 g/L. Blood cultures were negative. Immunological studies showed a negative antinuclear antibody, and a normal rheumatoid factor. There was no history of previously diagnosed sexually transmitted diseases in either the patient or her sexual partner. She denied any recreational illicit drug use and only occasionally drank alcohol. She was a non-smoker. Her only regular medication was the oral contraceptive pill. In the absence of other infectious or autoimmune diagnoses, an adverse drug reaction to trimethoprim is most likely. Trimethoprim-induced aseptic meningitis has been described in previous case reports. The potential to produce this adverse effect has been shown to occur independently of the combination with sulphonamide drugs. Uveitis, by contrast, has been attributed to the systemic use of sulphonamide derivatives. Of interest, most of these cases were reported in people treated with co-trimoxazole, and none was re-challenged with trimethoprim alone to determine if this drug was capable of inducing uveitis. To our knowledge this is the first case report of trimethopriminduced uveitis. It is possible that this diagnosis is missed due to the frequent use of this drug in combination with sulphamethoxazole for which this particular adverse drug reaction has been well described.

PREVALENCE OF BARTONELLA HENSELAE BACTEREMIA, THE CAUSATIVE AGENT OF CAT SCRATCH DISEASE, IN AN AUSTRALIAN CAT POPULATION

&NA; In order to determine the prevalence of Bartonella henselae bacteremia in an Australian cat population we examined blood cultures on a group of Sydney cats. Cats referred to the Concord Animal Hospital for euthanasia were selected randomly for blood culture and serum sampling. Blood samples were lysed and centrifuged and then cultured for up to five weeks. Suspicious colonies were identified biochemically as probable B. henselae. Selected isolates were confirmed as B. henselae using the polymerase chain reaction. Of the cats accrued throughout Sydney, 27/77 (35%) were culture positive for B. henselae, of these 24/59 (40%) were feral cats and 3/18 (16%) were domestic. Most cats in the study were younger than one year (mean 9.9 months). Our study demonstrates that bacteremia with B. henselae is common in the metropolitan cat population and suggests that it is particularly prevalent among feral animals. By contrast Cat Scratch Disease (CSD) is a relatively uncommon clinical diagnosis in the Australian population. Explanations for this discrepancy may include poor transmission, low bacterial virulence and underdiagnosis. It is possible that feral animals are a greater potential risk source for this infection than domestic cats.

Disseminated Mucormycosis Due to Saksenaea vasiformis in an Immunocompetent Adult

A case of disseminated infection due to Saksenaea vasiformis in a previously well adult male is presented. The clinical presentation was that of septic shock with a distinctive rash. At postmortem, endocarditis and widespread dissemination were evident.

Fusidic acid in bone and joint infections

The prominence of staphylococci as the causative agent in bone and joint infections suggests that fusidic acid (FA) has a potentially important role in their treatment. FA has been studied in a broad range of orthopaedic infections, mostly in combination with other antimicrobials. For susceptible organisms, particularly Staphylococcus aureus, it has demonstrable efficacy in acute osteomyelitis, chronic osteomyelitis, specialised forms of osteomyelitis such as calcaneal and vertebral infection, septic arthritis, prosthetic and other device-related infections. A small number of studies have also examined the use of FA alone for the treatment of bone infections, with evidence of good efficacy, as well as the local application of FA in plaster-of-Paris (POP) beads, or incorporated into bone cement, again with promising results. Further studies are required to confirm the efficacy of FA in the treatment of orthopaedic infections caused by methicillin-resistant strains of S. aureus.

Vancomycin pharmacokinetics in patients with severe burn injuries

Vancomycin is used in patients with severe burns and methicillin-resistant Staphylococcus aureus (MRSA) infection. This study investigated vancomycin pharmacokinetics in people with burns in comparison to people without burns and examined the factors contributing to pharmacokinetic variability. This was a retrospective, case-control study of hospitalised burns patients compared with a control patient cohort administered vancomycin without burn injury. Vancomycin pharmacokinetic parameters were determined using therapeutic drug monitoring data and a population pharmacokinetic modelling approach employing a two-compartment pharmacokinetic model. The impact of patient characteristics on vancomycin clearance was explored. Vancomycin clearance was significantly higher (p<0.001) in burns patients (5.9+/-3.1L/h, n=37) when compared to control patients (3.4+/-1.8 L/h, n=33), as was estimated creatinine clearance, which was correlated to drug clearance in burns patients (r(2)=0.64). There was no significant change in volume of distribution between patient groups. The majority of patients received a dosing regimen of 1g twice daily, resulting in significantly (p=0.004) lower serum trough concentrations in patients with burns (median, 6.4 mg/L; range, 0.2-22.3mg/L) than control (median, 9.2mg/L; range, 4.0-29.8 mg/L). Higher clearance and lower serum vancomycin concentrations in people with severe burn may increase the risk of suboptimal bactericidal action and the development of resistance highlighting the need for dosage individualization.

Consensus guidelines for the treatment of invasive mould infections in haematological malignancy and haemopoietic stem cell transplantation, 2014

Mould species represent the pathogens most commonly associated with invasive fungal disease in patients with haematological malignancies and patients of haemopoietic stem cell transplants. Invasive mould infections in these patient populations, particularly in the setting of neutropenia, are associated with high morbidity and mortality, and significantly increase the complexity of management. While Aspergillus species remain the most prevalent cause of invasive mould infections, Scedosporium and Fusarium species and the Mucormycetes continue to place a significant burden on the immunocompromised host. Evidence also suggests that infections caused by rare and emerging pathogens are increasing within the setting of broad-spectrum antifungal prophylaxis and improved survival times placing immunosuppressed patients at risk for longer. These guidelines present evidence-based recommendations for the antifungal management of common, rare and emerging mould infections in both adult and paediatric populations. Where relevant, the role of surgery, adjunctive therapy and immunotherapy is also discussed.

Molecular Epidemiology of Enterococcal Bacteremia in Australia

ABSTRACT Enterococci are a major cause of health care-associated infections and account for approximately 10% of all bacteremias globally. The aim of this study was to determine the proportion of enterococcal bacteremia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterize the molecular epidemiology of the Enterococcus faecalis and Enterococcus faecium isolates. From 1 January to 31 December 2011, 1,079 unique episodes of bacteremia were investigated, of which 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). The majority of bacteremias were health care associated, and approximately one-third were polymicrobial. Ampicillin resistance was detected in 90.4% of E. faecium isolates but was not detected in E. faecalis isolates. Vancomycin nonsusceptibility was reported in 0.6% and 36.5% of E. faecalis and E. faecium isolates, respectively. Unlike Europe and the United States, where vancomycin resistance in E. faecium is predominately due to the acquisition of the vanA operon, 98.4% of E. faecium isolates harboring van genes carried the vanB operon, and 16.1% of the vanB E. faecium isolates had vancomycin MICs at or below the susceptible breakpoint of the CLSI. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis pulsotypes, >50% belonged to two pulsotypes that were isolated across Australia. E. faecium consisted of 73 pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium isolates were identified as CC17 clones, of which approximately half were characterized as ST203, which was isolated Australia-wide. In conclusion, the Australian Enterococcal Sepsis Outcome Programme (AESOP) study has shown that although they are polyclonal, enterococcal bacteremias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.

Limited diversity in the gene pool allows prediction of third-generation cephalosporin and aminoglycoside resistance in Escherichia coli and Klebsiella pneumoniae

Early appropriate antibiotic treatment reduces mortality in severe sepsis, but current methods to identify antibiotic resistance still generally rely on bacterial culture. Modern diagnostics promise rapid gene detection, but the apparent diversity of relevant resistance genes in Enterobacteriaceae is a problem. Local surveys and analysis of publicly available data sets suggested that the resistance gene pool is dominated by a relatively small subset of genes, with a very high positive predictive value for phenotype. In this study, 152 Escherichia coli and 115 Klebsiella pneumoniae consecutive isolates with a cefotaxime, ceftriaxone and/or ceftazidime minimum inhibitory concentration (MIC) of ≥ 2 μg/mL were collected from seven major hospitals in Sydney (Australia) in 2008-2009. Nearly all of those with a MIC in excess of European Committee on Antimicrobial Susceptibility Testing (EUCAST) resistance breakpoints contained one or more representatives of only seven gene types capable of explaining this phenotype, and this included 96% of those with a MIC ≥ 2 μg/mL to any one of these drugs. Similarly, 97% of associated gentamicin-non-susceptibility (MIC ≥ 8 μg/mL) could be explained by three gene types. In a country like Australia, with a background prevalence of resistance to third-generation cephalosporins of 5-10%, this equates to a negative predictive value of >99.5% for non-susceptibility and is therefore suitable for diagnostic application. This is an important proof-of-principle that should be tested in other geographic locations.