Prevalence of HIV indicator conditions in late presenting patients with HIV: a missed opportunity for diagnosis?

AIM: To evaluate prior prevalence of HIV indicator conditions in late-presenters with HIV infection. DESIGN: Retrospective cohort study between 2000 and 2014 in a healthcare network in Melbourne, Australia comparing patients presenting with late diagnosis of HIV infection (CD4 < 350 cells/ml) to those patients who had a CD greater than or equal to 350 cells/ml at presentation. METHOD: The European AIDS Clinical Society guidelines on HIV indicator guided testing were used to assess for any indicator conditions in their prior medical history which may have represented a missed opportunity for earlier diagnosis. Main outcome measures: Descriptive statistics and prevalence of HIV indicator conditions. RESULTS: Of 436 patients with HIV infection, 82 were late presenters. Late presenters were more commonly male (83% vs. 75%, P = 0.11), older (mean age 45 vs. 39 years), born overseas (61% vs. 58%, P = 0.68) and report heterosexual transmission as their exposure risk (51% vs. 31%, P < 0.001). Of 80 patients with late presentation of HIV infection, 54 (55%) had at least one, 29 (36%) at least 2, 12 (15%) at least 3 and 5 (6%) had 4 or more previous HIV indicator conditions which would have triggered HIV testing according to guidelines. The most common indicator conditions were: unexplained loss of weight (31%), herpes zoster (10%), thrombocytopenia or leukopenia (10%), oral or oesophageal candidiasis (10%) and community acquired pneumonia (9%). Twenty patients (25%) had HIV indicator conditions diagnosed at least 12 months before the eventual diagnosis of HIV infection. DISCUSSION/ CONCLUSION: Patients diagnosed with late-presenting HIV often had an HIV indicator condition prior to presentation, presenting a missed opportunity for earlier diagnosis.

Australasian Society of Infectious Diseases updated guidelines for the management of Clostridium difficile infection in adults and children in Australia and New Zealand.

The incidence of Clostridium difficile infection (CDI) continues to rise, whilst treatment remains problematic due to recurrent, refractory and potentially severe nature of disease. The treatment of C. difficile is a challenge for community and hospital-based clinicians. With the advent of an expanding therapeutic arsenal against C. difficile since the last published Australasian guidelines, an update on CDI treatment recommendations for Australasian clinicians was required. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children.

Mucormycosis in Australia: contemporary epidemiology and outcomes.

Mucormycosis is the second most common cause of invasive mould infection and causes disease in diverse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004-2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1-42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8; 87.5% versus 10/66; 15.2%; p <0.001). Disseminated infection was common (39.2%). Apophysomyces spp. and Saksenaea spp. caused infection in immuno-competent hosts, most frequently associated with trauma and affected sites other than lung and sinuses. The 180-day mortality was 56.7%. The strongest predictors of mortality were rheumatological/autoimmune disorder (OR = 24.0, p 0.038 95% CI 1.2-481.4), haematological malignancy (OR = 7.7, p 0.001, 95% CI 2.3-25.2) and admission to intensive care unit (OR = 4.2, p 0.02, 95% CI 1.3-13.8). Most deaths occurred within one month. Thereafter we observed divergence in survival between the haematological and non-haematological populations (p 0.006). The mortality of mucormycosis remains particularly high in the immuno-compromised host. Underlying rheumatological/autoimmune disorders are a previously under-appreciated risk for infection and poor outcome.

Low rates of endocarditis in healthcare-associated Staphylococcus aureus bacteremia suggest that echocardiography might not always be required.

Healthcare-associated Staphylococcus aureus bacteremia (HA-SAB) is an increasingly frequently observed complication of medical treatment. Current guidelines recommend evaluation with echocardiography and preferably transesophageal echocardiography for the exclusion of infectious endocarditis (IE). We performed a retrospective analysis of all patients with HA-SAB between 1 January 2007 and 31 July 2012. Patients were divided into those with a high degree of clinical suspicion of IE (prosthetic intracardiac device, hemodialysis or positive blood cultures for 4 days or more) or those with a low degree of clinical suspicion of IE (absence of high-risk features based on previous literature as strong indicators of endocarditis). Three hundred and fifty-eight patients with HA-SAB were evaluated to determine the prevalence of IE, including 298 (83 %) who had echocardiography. Fourteen patients (4 %) had a final diagnosis of IE after echocardiography. In the group with a high degree of clinical suspicion 11 out of 84 patients (13 %) had IE. In the group with a low degree of clinical suspicion group 3 out 274 patients (1.1 %) had IE. HA-SAB has a low rate of IE, especially in the absence of high-risk features such as prolonged bacteremia, intracardiac prosthetic devices, and hemodialysis. Echocardiographic imaging in this low-risk population of patients is rarely helpful and may generally be avoided, although careful clinical follow-up is warranted. Patients with HA-SAB who have mechanical valves, intracardiac devices, prolonged bacteremia or dialysis dependency have a high incidence of IE and should be evaluated thoroughly using echocardiography.

Emergence and spread of predominantly community-onset Clostridium difficile PCR ribotype 244 infection in Australia, 2010 to 2012.

We describe an Australia-wide Clostridium difficile outbreak in 2011 and 2012 involving the previously uncommon ribotype 244. In Western Australia, 14 of 25 cases were community-associated, 11 were detected in patients younger than 65 years, 14 presented to emergency/outpatient departments, and 14 to non-tertiary/community hospitals. Using whole genome sequencing, we confirm ribotype 244 is from the same C. difficile clade as the epidemic ribotype 027. Like ribotype 027, it produces toxins A, B, and binary toxin, however it is fluoroquinolone-susceptible and thousands of single nucleotide variants distinct from ribotype 027. Fifteen outbreak isolates from across Australia were sequenced. Despite their geographic separation, all were genetically highly related without evidence of geographic clustering, consistent with a point source, for example affecting the national food chain. Comparison with reference laboratory strains revealed the outbreak clone shared a common ancestor with isolates from the United States and United Kingdom (UK). A strain obtained in the UK was phylogenetically related to our outbreak. Follow-up of that case revealed the patient had recently returned from Australia. Our data demonstrate new C. difficile strains are an on-going threat, with potential for rapid spread. Active surveillance is needed to identify and control emerging lineages.

Invasive infections due to filamentous fungi other than Aspergillus: epidemiology and determinants of mortality.

The epidemiology of invasive fungal disease (IFD) due to filamentous fungi other than Aspergillus may be changing. We analysed clinical, microbiological and outcome data in Australian patients to determine the predisposing factors and identify determinants of mortality. Proven and probable non-Aspergillus mould infections (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria) from 2004 to 2012 were evaluated in a multicentre study. Variables associated with infection and mortality were determined. Of 162 episodes of non-Aspergillus IFD, 145 (89.5%) were proven infections and 17 (10.5%) were probable infections. The pathogens included 29 fungal species/species complexes; mucormycetes (45.7%) and Scedosporium species (33.3%) were most common. The commonest comorbidities were haematological malignancies (HMs) (46.3%) diabetes mellitus (23.5%), and chronic pulmonary disease (16%); antecedent trauma was present in 21% of cases. Twenty-five (15.4%) patients had no immunocompromised status or comorbidity, and were more likely to have acquired infection following major trauma (p <0.01); 61 (37.7%) of cases affected patients without HMs or transplantation. Antifungal therapy was administered to 93.2% of patients (median 68 days, interquartile range 19-275), and adjunctive surgery was performed in 58.6%. The all-cause 90-day mortality was 44.4%; HMs and intensive-care admission were the strongest predictors of death (both p <0.001). Survival varied by fungal group, with the risk of death being significantly lower in patients with dematiaceous mould infections than in patients with other non-Aspergillus mould infections. Non-Aspergillus IFD affected diverse patient groups, including non-immunocompromised hosts and those outside traditional risk groups; therefore, definitions of IFD in these patients are required. Given the high mortality, increased recognition of infections and accurate identification of the causative agent are required.

Who really knows their patients' penicillin adverse drug reaction status? A cross-sectional survey.

This cross-sectional survey of patients with adverse drug reactions (ADR) to penicillin and their treating doctor, nurse and pharmacist was undertaken to identify the extent of healthcare workers (HCW) awareness of their patients' ADR, and antibiotic use in hospital. There were 23 (38%) doctors, 53 (87%) nurses and 40 (66%) pharmacists who were aware of their patient's penicillin ADR, despite more than half of their patients receiving antibiotics. Interventions encouraging 'double checking' may improve antibiovigilance.

Clinical and microbiological characteristics of Eggerthella lenta bacteremia.

Eggerthella lenta is an emerging pathogen that has been underrecognized due to historical difficulties with phenotypic identification. Until now, its pathogenicity, antimicrobial susceptibility profile, and optimal treatment have been poorly characterized. In this article, we report the largest cohort of patients with E. lenta bacteremia to date and describe in detail their clinical features, microbiologic characteristics, treatment, and outcomes. We identified 33 patients; the median age was 68 years, and there was no gender predominance. Twenty-seven patients (82%) had serious intra-abdominal pathology, often requiring a medical procedure. Of those who received antibiotics (28/33, 85%), the median duration of treatment was 21.5 days. Mortality from all causes was 6% at 7 days, 12% at 30 days, and 33% at 1 year. Of 26 isolates available for further testing, all were identified as E. lenta by both commercially available matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) systems, and none were found to harbor a vanA or vanB gene. Of 23 isolates which underwent susceptibility testing, all were susceptible to amoxicillin-clavulanate, cefoxitin, metronidazole, piperacillin-tazobactam, ertapenem, and meropenem, 91% were susceptible to clindamycin, 74% were susceptible to moxifloxacin, and 39% were susceptible to penicillin.

Eggerthella lenta bacteremia complicated by spondylodiscitis, psoas abscess, and meningitis.

Eggerthella lenta bacteremia is uncommon and generally associated with abdominal sepsis. The organism and its clinical significance have not been well characterized due to historical difficulties with identification. We report a case of severe infection in a paraplegic man complicated by psoas abscess, osteomyelitis, and meningitis and discuss treatment challenges.

Hampered by historical paradigms--echinocandins and the treatment of Candida endocarditis.

Infective endocarditis due to Candida sp. has a high mortality rate. Traditionally, management involves early surgery and prolonged amphotericin ± flucytosine. We report a case of Candida parapsilosis bileaflet mitral valve endocarditis cured with anidulafungin and fluconazole, and review the role of echinocandins in the management of Candida endocarditis.

Vancomycin-resistant enterococci colonization does not increase mortality in end-stage kidney failure: a case-control study.

BACKGROUND: Vancomycin-resistant enterococci (VRE) colonization is a frequent occurrence in patients with renal failure. Understanding the impact of VRE colonization on this group of patients has considerable clinical applicability. AIM: To understand whether VRE colonization in renal patients has an impact on number of admissions to hospital, length of stay, and mortality. METHODS: A retrospective case-control study of renal dialysis patients was performed between 2000 and 2010. Cases were 134 VRE-colonized patients requiring renal replacement therapy and matched controls were 137 non-colonized patients with the same baseline characteristics. Matched cases and controls were analysed for differences in number of admissions, length of stay, and mortality. FINDINGS: There was no difference in mortality between colonized and non-colonized patients (hazard ratio: 1.14; 95% confidence interval: 0.78-1.69; P = 0.49). Length of stay for colonized patients was 7.29 days compared with 4.14 days (P < 0.001). The number of admissions for VRE-colonized patients was not significantly different compared with controls (9.34 vs 8.33, P = 0.78). CONCLUSION: VRE colonization did not increase mortality in renal patients but did contribute to increased length of stay.

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.

New HIV diagnosis after occupational exposure screening: the importance of reporting needlestick injuries.

We describe three new diagnosis of HIV infection as a direct result of testing following occupational exposures (NSIs) in a low-prevalence setting. In each case the finding was unexpected. Our series provides a reminder of the importance of prompt reporting of NSIs by healthcare workers, access to rapid HIV testing and post-exposure prophylaxis with antiretrovirals to prevent transmission.

Rat bite fever as a presenting illness in a patient with AIDS.

The etiology of culture-negative septic arthritis is poorly characterised in persons infected with human immunodeficiency virus (HIV). New molecular methods may assist in the investigation of culture-negative infections of sterile sites, including septic arthritis. We describe the first case of septic arthritis due to the cause of rat bite fever (RBF), Streptobacillus moniliformis, confirmed by 16S rRNA sequence analysis, in a patient with newly diagnosed HIV infection.

Rat-bite fever septic arthritis: illustrative case and literature review.

Rat-bite fever is a rare zoonotic infection caused by Streptobacillus moniliformis or Spirillum minus, which is characterised by fever, rash and arthritis. The arthritis has previously been described as non-suppurative and isolation of the organism from synovial fluid as very uncommon. This article reports a case of septic arthritis diagnosed as rat-bite fever when the organism was cultured from synovial fluid and reviews another 15 cases of S. moniliformis septic arthritis reported in the worldwide literature since 1985. Articles were included in this review if S. moniliformis was cultured from synovial fluid. Of the published cases, 88% presented with polyarthritis, affecting small and large joints although two had monoarticular hip sepsis. Fever was present in 88%, rash in 25% and 56% had extra-articular features. Synovial fluid analysis revealed high cell counts in all cases (mean 51,000 x 10(9)/l) with a predominance of polymorphonuclear leucocytes, and organisms were found on Gram stain in only 50%. Penicillin was used for treatment in 56% of cases and surgery was required in 30%. All patients recovered. Rat-bite fever arthritis can be suppurative and attempts should be made to isolate the organism from synovial fluid. The diagnosis should be considered when there is arthritis and a high synovial fluid cell count but no apparent organism, especially when the patient has had contact with rats.

Management of Aspergillus osteomyelitis: report of failure of liposomal amphotericin B and response to voriconazole in an immunocompetent host and literature review.

Presented here is a case of Aspergillus osteomyelitis in an immunocompetent patient that progressed despite surgery and prolonged treatment with liposomal amphotericin B; the report is followed by a review of the literature. The review of this case and 41 similar cases found an overall cure rate of 69%. The importance of surgery when amphotericin B is used as first-line therapy is indicated by a 14% cure rate when amphotericin B is used alone compared to 75% when combined with surgery. When therapy is failing or surgery is contraindicated, dose escalation using a lipid formulation was not effective. On review, the addition of another agent, in particular 5-fluorocytosine, appears to be more beneficial. The patient reported here responded rapidly to voriconazole, a promising new antifungal agent for Aspergillus infections.

Bacteraemia due to Stenotrophomonas maltophilia: an analysis of 45 episodes.

OBJECTIVE: Stenotrophomonas maltophilia is an important nosocomial pathogen and a therapeutic challenge. A ten-year review of episodes of bacteraemia due to S. maltophilia was undertaken in light of reports of an increasing frequency of infection. METHODS: A retrospective analysis of bloodstream infections due toS. maltophilia at a tertiary care hospital in Melbourne, Australia. Cases were identified via microbiology laboratory reports, and relevant clinical data were collected from the medical record of each patient. RESULTS: Eighty per cent of these 45 episodes were nosocomial. The most common characteristics in cases of bacteraemia were the presence of an indwelling central venous catheter (CVC) (38/45, 84%) and previous antibiotic therapy (33/45, 73%). There were 8 deaths (8/44, 18%) within 7 days of bacteraemia. A significant correlation was found between deaths and a failure to remove the CVC (P = 0.01) or treat with appropriate antimicrobials (P = 0.01). Antibiotic susceptibility testing revealed that isolates were most sensitive to sulphamethoxazole (80%), chloramphenicol (75.5%) and ceftazidime (64.5%). CONCLUSIONS: S. maltophilia is an important pathogen especially in the highly compromised host. Isolation of this organism from a blood culture should prompt a careful review of the patient with particular emphasis on removal of indwelling CVCs and commencement of appropriate antibiotic therapy.