Vancomycin minimum inhibitory concentration, host comorbidities and mortality in Staphylococcus aureus bacteraemia.

We reported an association between elevated vancomycin MIC and 30-day mortality in patients with Staphylococcus aureus bacteraemia (SAB), including patients with methicillin-susceptible S. aureus (MSSA) treated with flucloxacillin. A detailed analysis of comorbidities and disease severity scores in the same cohort of patients was performed to ascertain if unknown clinical parameters may have influenced these results. The association between elevated vancomycin MIC and 30-day mortality in SAB remained significant (p 0.001) on multivariable logistic regression analysis even when accounting for clinical factors. In addition, the association persisted when restricting analysis to patients with MSSA bacteraemia treated with flucloxacillin. This suggests that elevated vancomycin MIC is associated with but not causally linked to an organism factor that is responsible for increased mortality.

Nasal carriage of Staphylococcus aureus, including community-associated methicillin-resistant strains, in Queensland adults.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are emerging in southeast Queensland, Australia, but the incidence of carriage of CA-MRSA strains is unknown. The aim of this study was to assess the nasal carriage rate of S. aureus, including CA-MRSA strains, in the general adult population of southeast Queensland. 396 patients presenting to general practices in two Brisbane suburbs and 303 volunteers randomly selected from the electoral rolls in the same suburbs completed a medical questionnaire and had nasal swabs performed for S. aureus. All isolates of S. aureus underwent antibiotic susceptibility testing and single-nucleotide polymorphism (SNP) and binary typing, including determination of Panton-Valentine leukocidin (PVL). The nasal carriage rate of methicillin-susceptible S. aureus (MSSA) was 202/699 (28%), a rate similar to that found in other community-based nasal carriage studies. According to multivariate analysis, nasal carriage of S. aureus was associated with male sex, young adult age group and Caucasian ethnicity. Only two study isolates (one MSSA and one CA-MRSA) carried PVL. The nasal carriage rate of MRSA was low, at 5/699 (0.7%), and only two study participants (0.3%) had CA-MRSA strains. CA-MRSA is an emerging cause of infection in southeast Queensland, but as yet the incidence of carriage of CA-MRSA in the general community is low.

Cavernous sinus thrombosis and meningitis from community-acquired methicillin-resistant Staphylococcus aureus infection.

Septic cavernous sinus thrombosis is an uncommon clinical syndrome with a high morbidity and mortality. The commonest bacterial pathogen is Staphylococcus aureus. We describe the study of a patient with cavernous sinus thrombosis and meningitis caused by community-acquired methicillin-resistant S. aureus (CA-MRSA) infection. The isolate was genotyped as the ST93 (Queensland) clone of CA-MRSA and carried the Panton-Valentine leucocidin genes. Cure was obtained following prolonged antimicrobial therapy with vancomycin, rifampicin, cotrimoxazole and linezolid. Given the high morbidity and mortality of cavernous sinus thrombosis and the worldwide recent emergence of CA-MRSA, clinicians treating patients with this infection should consider early empirical coverage for CA-MRSA with an antimicrobial agent, such as vancomycin or linezolid, particularly in the presence of suspected facial staphylococcal skin infections. If vancomycin is used, we emphasize that high doses may be required to achieve even low levels in the cerebrospinal fluid.

Methicillin-susceptible, non-multiresistant methicillin-resistant and multiresistant methicillin-resistant Staphylococcus aureus infections: a clinical, epidemiological and microbiological comparative study.

Non-multiresistant methicillin-resistant Staphylococcus aureus (nmMRSA) infections are emerging worldwide and are often community-associated. This prospective case-cohort study compares features of 96 nmMRSA clinical isolates with 96 matched multiresistant MRSA (mMRSA) and 192 matched methicillin-susceptible S. aureus (MSSA) clinical isolates. Seventy-four percent of nmMRSA infections were healthcare-associated. nmMRSA infections were much more likely to involve skin and soft tissue (skin and soft tissue infections; SSTIs) and were much less likely to be treated appropriately with antibiotics than MSSA or mMRSA infections. Panton-Valentine leukocidin (PVL) genes were detected in 55% of nmMRSA, 16% of MSSA and 2% of mMRSA isolates. Independent of the methicillin-resistance phenotype, 59% of PVL-positive SSTIs presented as furunculosis compared to only 10% of PVL-negative SSTIs. Patients with PVL-positive infections were much younger than patients with PVL-negative infections. The proportion of PVL-positive infections peaked in the 10-29 years old age group, followed by a linear decline.

Two rare severe and fulminant presentations of Q fever in patients with minimal risk factors for this disease.

We described two rare severe and fulminant clinical presentations of acute Q fever. The first patient had severe multiorgan failure. The second patient had fever and severe cholera-like diarrhoea. Coxiella burnetii polymerase chain reaction on blood or serum can be clinically useful in the diagnosis of acute Q fever before seroconversion.

Antibiotics currently used in the treatment of infections caused by Staphylococcus aureus.

Staphylococcal infections are a common and significant clinical problem in medical practice. Most strains of Staphylococcus aureus are now resistant to penicillin, and methicillin-resistant strains of S. aureus (MRSA) are common in hospitals and are emerging in the community. Penicillinase-resistant penicillins (flucloxacillin, dicloxacillin) remain the antibiotics of choice for the management of serious methicillin-susceptible S. aureus (MSSA) infections, but first generation cephalosporins (cefazolin, cephalothin and cephalexin), clindamycin, lincomycin and erythromycin have important therapeutic roles in less serious MSSA infections such as skin and soft tissue infections or in patients with penicillin hypersensitivity, although cephalosporins are contra-indicated in patients with immediate penicillin hypersensitivity (urticaria, angioedema, bronchospasm or anaphylaxis). All serious MRSA infections should be treated with parenteral vancomycin or, if the patient is vancomycin allergic, teicoplanin. Nosocomial strains of MRSA are typically multi-resistant (mrMRSA), and mrMRSA strains must always be treated with a combination of two oral antimicrobials, typically rifampicin and fusidic acid, because resistance develops rapidly if they are used as single agents. Most community-acquired strains of MRSA in Australia and New Zealand are non multiresistant (nmMRSA), and lincosamides (clindamycin, lincomycin) or cotrimoxazole are the antibiotics of choice for less serious nmMRSA infections such as skin and soft tissue infections. New antibiotics such as linezolid and quinupristin/dalfopristin have good antistaphylococcal activity but are very expensive and should be reserved for patients who fail on or are intolerant of conventional therapy or who have highly resistant strains such as hVISA (heterogenous vancomycin-intermediate S aureus).

Life-threatening community-acquired methicillin-resistant Staphylococcus aureus infection in Australia.

Eight patients with invasive bacteremic community-acquired methicillin-resistant Staphylococcus aureus infection in southeast Queensland, Australia, are reported. One patient died of septic shock. Haematogenous seeding to lungs, bone, and other sites was common. All isolates carried the virulence factor Panton-Valentine leukocidin and were either the southwest Pacific clone or the newly described Queensland clone. Clinicians should consider community-acquired methicillin-resistant Staphylococcus aureus infection in any patient presenting to hospital with severe staphylococcal sepsis or pneumonia.

A cluster of tuberculosis associated with use of a marijuana water pipe.

SETTING: New cases of pulmonary tuberculosis (TB) were noted in a cluster of young Caucasian males, an unusual ethnic group for this disease in Queensland, Australia. It was noted that marijuana water pipe ('bong') smoking was common amongst cases and contacts. OBJECTIVE: To report this cluster of TB and to investigate whether shared use of a marijuana water pipe was associated with transmission of TB. DESIGN: All contacts were identified and screened according to standard protocols. Cases were asked to list contacts with whom they had shared a marijuana water pipe. RESULTS: Five cases of open pulmonary TB were identified clinically and on sputum culture, and all isolates of Mycobacterium tuberculosis were identical on typing. Of 149 contacts identified, 114 (77%) completed screening, and 57 (50%) had significant tuberculin skin test (TST) reactions on follow-up. Of 45 contacts who had shared a marijuana water pipe with a case, 29 (64%) had a significant TST reaction. CONCLUSION: Sharing a marijuana water pipe with a case of pulmonary TB was associated with transmission of TB (OR 2.22, 95 % CI 0.96-5.17), although the most important risk factor for acquiring TB infection in this cluster was close household contact with a case (OR 4.91, 95% CI 1.13-20.70).

Fatal human melioidosis acquired in a subtropical Australian city.

We describe an acute fatal human case of melioidosis acquired in Ipswich, a city at 27.5 degrees S in southern Queensland, south of the area traditionally considered endemic for melioidosis in Australia. Molecular typing revealed that this patient isolate was genetically distinct from 2 other human and 1 bovine isolates of Burkholderia pseudomallei from the same region and from 4 tropical northern Australian strains. This finding suggests that if B. pseudomallei has been introduced to the region from northern Australia, it was not in recent times, and there has not been a point source of infection. Burkholderia pseudomallei is present in temperate southern Queensland, which hitherto has not been well appreciated. Clinicians should consider the diagnosis of acute melioidosis in patients with severe pneumonia or septicemia acquired in subtropical areas such as southern Queensland, particularly after heavy summer rains with flooding.

Post-antibiotic growth suppression of linezolid against Gram-positive bacteria.

The in vitro post-antibiotic effects (PAEs) of eight different concentrations of linezolid against Gram-positive cocci were investigated and the results analysed using the sigmoid E(max) model for mathematically modelling the PAE. Mean maximal linezolid PAEs against strains of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium and Streptococcus pneumoniae were 2.2, 1.8, 2.8, 2.0 and 3.0 h, respectively. Resistance to methicillin (for the staphylococci), vancomycin (for the enterococci) and penicillin (for the pneumococci) had no effect on the duration of the PAE. Results of PAE testing support twice-daily dosing of linezolid in humans.

Postantibiotic suppression of growth of erythromycin A-susceptible and -resistant gram-positive bacteria by the ketolides telithromycin (HMR 3647) and HMR 3004.

We investigated the in vitro postantibiotic effects (PAEs) of the ketolides telithromycin (HMR 3647) and HMR 3004 and analyzed the results using the sigmoid E(max) model. Mean maximum telithromycin PAEs against erythromycin A-susceptible strains of Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae were 3. 7, 8.9, and 9.7 h, respectively, while maximum PAEs for erythromycin A-resistant strains were much shorter. Mean maximum HMR 3004 PAEs were 3.2 to 4.4 h for all species.

Concurrent prescribing. Beware of drug interactions.

BACKGROUND: Antibiotics are commonly prescribed to patients who are also taking other medications. Pharmacology textbooks contain long lists of potential interactions between antibiotics and other drugs, but only a few of these interactions have serious clinical consequences. OBJECTIVE: This review will highlight antibiotic interactions that are clinically significant, and the relative incidence and importance of each interaction will be considered. It will concentrate primarily on drugs commonly prescribed in general practice, such as the oral contraceptive pill and warfarin. DISCUSSION: Quinolones and macrolides are the groups of antibiotics most commonly associated with clinically significant drug interactions. Warfarin interacts with many antibiotics, although the incidence of this interaction can range from predictable to rare. The association between most antibiotics and oral contraceptive failure is weak, with only sporadic case reports in the literature.

The postantibiotic effect of fusidic acid against gram-positive bacteria.

The in-vitro postantibiotic effect (PAE) of fusidic acid was tested for six strains of Staphylococcus aureus and four strains of Streptococcus pyogenes. The maximum PAE that could be achieved was more than 3 h, but at concentrations of antibiotic attainable in humans, the PAE was less than 2 h. Additional experiments were performed in albumin, to examine the effect of the strong protein binding of fusidic acid on the MIC and PAE. MICs were increased, but at the same multiple of the MIC, PAEs were similar to those performed in Mueller-Hinton broth.

The postantibiotic effect of imipenem: relationship with drug concentration, duration of exposure, and MIC.

The postantibiotic effect (PAE) of imipenem against Escherichia coli was measured at a wide variety of drug concentrations and times of exposure. We observed that the area under the concentration-time curve of drug exposure (AUC), the product of time of exposure and concentration of drug, is a much better predictor of the duration of the PAE than either parameter alone. We also measured the PAE of imipenem against strains of gram-positive and gram-negative bacteria for which MICs varied widely. The E50, the AUC required to produce 50% of the maximum PAE, is correlated with the MIC and is independent of species. This may explain why the duration of the PAE differs for bacteria of the same species for which MICs are different.

A meta-analysis of studies on the safety and efficacy of aminoglycosides given either once daily or as divided doses.

We performed a meta-analysis of randomised clinical studies in which the efficacy and toxicity of the same total daily dose of aminoglycosides administered once-daily was compared with multiple divided daily dosing for treating human infections. Of twenty-eight publications identified from a literature search using Medline 19 publications of 20 study comparisons involving 2881 patients met the criteria for analysis. Netilmicin was investigated in 11 studies, amikacin in seven studies and gentamicin in two studies but no studies of tobramycin met the inclusion criteria. The meta-analysis showed that there was a small, statistically significant difference in clinical efficacy of 3.5% (95% confidence intervals 0.5% to 6.5%, P = 0.027) in favour of once-daily administration but no significant differences in bacteriological efficacy or nephrotoxicity were detected. Auditory and vestibular toxicity rates were low for all agents and no differences in these toxicities were identified between once-daily or multiple-dose administration regimens either clinically or by audiometry or electronystagmography. Aminoglycosides can be given once-daily without loss of efficacy or increased toxicity offering greater simplicity and potentially improved cost-effectiveness than can be achieved by giving these drugs in divided doses.