Leon J. Worth

Spectrum of infection, risk and recommendations for prophylaxis and screening among patients with lymphoproliferative disorders treated with alemtuzumab*.

There is an increasing use of monoclonal antibodies in the treatment of haematological malignancies. Alemtuzumab (Campath‐1H; Ilex Pharmaceuticals, San Antonio, TX, USA) is a monoclonal antibody reactive with the CD52 antigen used as first and second line therapy for two types of lymphoproliferative disorders: chronic lymphocytic leukaemia (CLL), and T‐cell lymphomas [both peripheral (PTCL) and cutaneous (CTCL)]. With alemtuzumab therapy, viral, bacterial and fungal infectious complications are frequent, and may be life threatening. An understanding of the patients at highest risk and duration of risk are important in developing recommendations for empirical management, antimicrobial prophylaxis and targeted surveillance. This review discusses the infection risks associated with these lymphoproliferative disorders and their treatment, and provide detailed recommendations for screening and prophylaxis.

Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus, Australia.

Resistance in virus-infected stem cell transplant recipients illustrates the need for surveillance.

Vancomycin-resistant Enterococcus faecium infection in patients with hematologic malignancy: patients with acute myeloid leukemia are at high-risk.

Background:  Vancomycin‐resistant enterococci (VRE) are significant nosocomial pathogens in patients with hematologic malignancy. Identification of risk factors for infection is necessary for targeted prevention and surveillance.

Pneumocystis jirovecii pneumonia in non-HIV-infected patients: new risks and diagnostic tools.

Purpose of review Non-HIV-infected populations are increasingly identified as being at risk for developing Pneumocystis jirovecii pneumonia (PJP). These patients typically present with severe disease and poorly tolerate invasive diagnostic procedures. This review examines recently reported risks for PJP in non-HIV populations and summarizes new diagnostic techniques. Recent findings PJP is associated with immunomodulatory drug therapies, including monoclonal antibody therapies such as tumour necrosis factor &agr; antagonists, and calcineurin inhibitors. Underlying disease states include solid-organ transplantation, connective tissue and rheumatologic disorders, inflammatory bowel disease, haematological malignancies, and solid tumours. Modern diagnostic techniques [conventional PCR, quantitative PCR, (1→3)-&bgr;-D-glucan assays, and PET] are reviewed with respect to predictive value and clinical utility. In particular, current literature regarding validation and specificity of molecular diagnostic techniques is summarized, including application to minimally invasive specimens. Summary HIV-negative populations at risk for PJP can be identified. Conventional PCR increases diagnostic sensitivity but may detect asymptomatic colonization. Quantitative PCR demonstrates potential for distinguishing colonization from infection, but clinical validation is required. Serum (1→3)-&bgr;-D-glucan may be elevated in PJP, although standardized cut-off values for clinical infection have not been determined. Further validation of serum markers and molecular diagnostic methods is necessary for early and accurate diagnosis in non-HIV populations.

Epidemiology of Infections Acquired in Intensive Care Units

Infections acquired in the intensive care unit (ICU) are associated with significant morbidity and mortality. Using surveillance data collected in the United States and internationally, we describe contemporary rates, sites, and pathogens responsible for common ICU-acquired infections. Emerging pathogens are outlined, including a systematic review of published ICU infection outbreaks from 2005 to 2010. Compared with a similar review of outbreaks conducted in 2003, multiresistant gram-negative bacteria (eg, ACINETOBACTER and PSEUDOMONAS species) were more commonly reported, whereas resistant STAPHYLOCOCCUS AUREUS was reported less frequently. Advances in ICU infection prevention, including central line bundles, chlorhexidine body wash, and hand hygiene interventions occurred during this period. We also describe how changes in the pattern of antimicrobial use can affect the prevalence of multiresistant pathogens.

Increasing incidence of Clostridium difficile infection, Australia, 2011-2012

Objectives: To report the quarterly incidence of hospital‐identified Clostridium difficile infection (HI‐CDI) in Australia, and to estimate the burden ascribed to hospital‐associated (HA) and community‐associated (CA) infections.

An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital

Pneumocystis jirovecii pneumonia (PCP) is associated with high mortality in immunocompromised patients without human immunodeficiency virus infection. However, chemoprophylaxis is highly effective. In patients with solid tumours or haematologic malignancy, several risk factors for developing PCP have been identified, predominantly corticosteroid therapy. The aims of this study were to identify the potentially preventable cases of PCP in patients receiving corticosteroid therapy at a tertiary care cancer centre and to estimate the frequency of utilisation of chemoprophylaxis in these patients. Two retrospective reviews were performed. Over a 10-year period, 14 cases of PCP were identified: no cases were attributable to failed chemoprophylaxis, drug allergy or intolerance. During a 6-month period, 73 patients received high-dose corticosteroid therapy (⩾25 mg prednisolone or ⩾4 mg dexamethasone daily) for ⩾4 weeks. Of these, 22 (30%) had haematologic malignancy, and 51 (70%) had solid tumours. Fewer patients with solid tumours received prophylaxis compared to patients with haematologic malignancy (3.9 vs 63.6%, P<0.0001). Guidelines for PCP chemoprophylaxis in patients with haematologic malignancy or solid tumours who receive corticosteroid therapy are proposed. Successful primary prevention of PCP in this population will require a multifaceted approach targeting the suboptimal prescribing patterns for chemoprophylaxis.

Stenotrophomonas maltophilia: emerging disease patterns and challenges for treatment

Stenotrophomonas maltophilia is a ubiquitous organism associated with opportunistic infections. In the immunocompromised host, increasing prevalence and severity of illness is observed, particularly opportunistic bloodstream infections and pneumonia syndromes. In this article, the classification and microbiology are outlined, together with clinical presentation, outcomes and management of infections due to S. maltophilia. Although virulence mechanisms and the genetic basis of antibiotic resistance have been identified, a role for standardized and uniform reporting of antibiotic sensitivity is not defined. Infections due to S. maltophilia have traditionally been treated with trimethoprim–sulfamethoxazole, ticarcillin–clavulanic acid, or fluoroquinolone agents. The use of combination therapies, newer fluoroquinolone agents and tetracycline derivatives is discussed. Finally, measures to prevent transmission of S. maltophilia within healthcare facilities are reported, especially in at-risk patient populations.

Validation of Statewide Surveillance System Data on Central Line–Associated Bloodstream Infection in Intensive Care Units in Australia

OBJECTIVE To measure the interobserver agreement, sensitivity, specificity, positive predictive value, and negative predictive value of data submitted to a statewide surveillance system for identifying central line-associated bloodstream infection (BSI). DESIGN Retrospective review of hospital medical records comparing reported data with gold standard according to definitions of central line-associated BSI. SETTING Six Victorian public hospitals with more than 100 beds. METHODS Reporting of surveillance outcomes was undertaken by infection control practitioners at the hospital sites. Retrospective evaluation of the surveillance process was carried out by independent infection control practitioners from the Victorian Hospital Acquired Infection Surveillance System (VICNISS). A sample of records of patients reported to have a central line-associated BSI were assessed to determine whether they met the definition of central line-associated BSI. A sample of records of patients with bacteremia in the intensive care unit during the assessment period who were not reported as having central line-associated BSI were also assessed to see whether they met the definition of central line-associated BSI. RESULTS Records of 108 patients were reviewed; the agreement between surveillance reports and the VICNISS assessment was 67.6% (k = 0.31). Of the 46 reported central line-associated BSIs, 27 were confirmed to be central line-associated BSIs, for a positive predictive value of 59% (95% confidence interval [CI], 43%-73%). Of the 62 cases of bacteremia reviewed that were not reported as central line-associated BSIs, 45 were not associated with a central line, for a negative predictive value of 73% (95% CI, 60%-83%). Estimated sensitivity was 35%, and specificity was 87%. The positive likelihood ratio was 3.0, and the negative likelihood ratio was 0.72. DISCUSSION The agreement between the reporting of central line-associated BSI and the gold standard application of definitions was unacceptably low. False-negative results were problematic; more than half of central line-associated BSIs may be missed in Victorian public hospitals.

Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy, 2014

Antifungal agents may be associated with significant toxicity or drug interactions leading to sub‐therapeutic antifungal drug concentrations and poorer clinical outcomes for patients with haematological malignancy. These risks may be minimised by clinical assessment, laboratory monitoring, avoidance of particular drug combinations and dose modification. Specific measures, such as the optimal timing of oral drug administration in relation to meals, use of pre‐hydration and electrolyte supplementation may also be required. Therapeutic drug monitoring (TDM) of antifungal agents is warranted, especially where non‐compliance, non‐linear pharmacokinetics, inadequate absorption, a narrow therapeutic window, suspected drug interaction or unexpected toxicity are encountered. Recommended indications for voriconazole and posaconazole TDM in the clinical management of haematology patients are provided. With emerging knowledge regarding the impact of pharmacogenomics upon metabolism of azole agents (particularly voriconazole), potential applications of pharmacogenomic evaluation to clinical practice are proposed.