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Infectious diseases Medical education 25 May 2020 Free

Candida auris in an Australian health care facility: importance of screening high risk patients

Clinical record A 70‐year‐old man with multiple myeloma was admitted to our hospital in 2018, having been hospitalised 10 months previously in the United Kingdom. Following admission to our facility, routine collection of clinical specimens was performed in the setting of an episode of febrile neutropenia. Candida auris was isolated in a urine specimen collected in the presence of an indwelling urinary catheter, without accompanying pyuria. Screening of ward contacts (n = 73) was subsequently performed by collection of composite axilla and groin skin swabs, together with swabbing of possible clinical sites of infection (eg, wounds, catheter sites). Swabs were plated onto Candida chromogenic agar and incubated aerobically for 48 hours at 35°C. Any colonies not typical for C. albicans or C. tropicalis were identified using matrix‐assisted laser desorption ionisation time‐of‐flight (MALDI‐TOF) mass spectrometry. The routine regimen of daily cleaning and disinfection of rooms with 1000 ppm sodium hypochlorite solution was continued. Enhanced infection control measures, including contact precautions and single‐room isolation were instituted. A multidisciplinary taskforce coordinated screening, laboratory and prevention strategies. Review of laboratory reports for the preceding 12 months confirmed this to be the first documented C. auris isolate at our facility. One ward contact, a 38‐year‐old man with diffuse large B cell lymphoma, was identified as colonised with C. auris. The organism was detected in a urine specimen collected in the presence of a long term indwelling urinary catheter. This patient had been admitted to a health care facility in the United Arab Emirates, before direct transfer to our facility about 3 months earlier. Colonised patients had been located in a common ward for 19 days, each in a single room with dedicated bathroom and patient care equipment. They had also been managed on an outlying ward for brief periods (3 and 2 days, respectively) separated in time by 2 days. Neither patient developed clinical features of urinary tract or disseminated C. auris infection and antifungal therapy was not administered. Isolates were confirmed as C. auris by MALDI‐TOF mass spectrometry (each with score of 1.75). Antifungal susceptibility testing by broth microdilution demonstrated isolates were resistant to fluconazole (minimum inhibitory concentration [MIC] > 256 mg/L) and susceptible to caspofungin (MIC, 0.25 mg/L) and anidulafungin (MIC, 0.12 mg/L for Patient 1 and 0.25 mg/L for Patient 2). To investigate relatedness of isolates, whole genome sequencing and bioinformatics analysis were performed. Phylogeographic analysis demonstrated that both were related globally to those contained in the India–Pakistan clade. The median pairwise single nucleotide polymorphism distance between the two isolates was 167, suggesting that while these isolates were related, it was not possible to confirm whether transmission had occurred. Discussion Candida auris is an emerging, drug‐resistant yeast, responsible for hospital outbreaks internationally.1 First recognised as a new species of Candida in 2009, cases have been reported in over 30 countries, including the United Kingdom and United Arab Emirates.1,2 In outbreak settings, bloodstream, urinary tract and deep tissue infections have been reported, in addition to colonisation. The majority of isolates are fluconazole resistant,3 with variable resistance to amphotericin B and the echinocandin class of antifungal agents. Infection is associated with a crude mortality of 30%.3 Key differences between C. albicans (the most frequently identified Candida species in Australia) and C. auris are summarised in the Box. Risks for C. auris acquisition include admission to a high dependency unit, presence of invasive medical devices, underlying immunocompromise or chronic disease and receipt of antibiotic or antifungal agents.4 One case of C. auris invasive disease has previously been reported in Australia,5 but to our knowledge the two cases identified at our facility represent the first possible transmission of C. auris in Australia. Identification of C. auris is challenging, with potential misidentification by routine biochemical methods. If C. auris is included in the reference profile database, MALDI‐TOF mass spectrometry may be used to confirm diagnosis. DNA sequencing also provides confirmation, together with data regarding origins and potential transmission in health care settings.3 Collection of bilateral axilla and groin skin swabs as a combined screening specimen is recommended for optimal yield.6 European and United States guidelines recommend screening of all room contacts of patients with C. auris.6,7 Screening of additional patients (eg, whole ward) is necessary where more than one case is identified. Targeted surveillance of patients who have recently had at least one overnight stay in an overseas facility is also recommended, especially if from a country reporting C. auris cases.6,7 Our experience highlights the importance of this strategy. Clinicians should be aware of risks for C. auris acquisition, including overseas health care encounters. In high risk settings, and where a case of C. auris infection has been identified, timely screening of patients is required to ensure that appropriate control measures are instituted. Lessons from practice Candida auris is an emerging drug‐resistant yeast, now reported in Australian health care facilities. In contrast to C. albicans, which is commonly isolated in community and health care settings, C. auris is generally only identified in high risk hospitalised populations. Risks for acquisition include intensive care or high dependency unit admission, presence of invasive medical devices, underlying immunocompromise or chronic disease, and receipt of broad spectrum antibiotics or antifungal agents. Strict infection control measures, including contact precautions and isolation, are required to reduce risks of transmission. Screening for colonisation is an important element of infection control strategies, and a composite skin swab of axilla and groin is recommended. Timely detection requires laboratory identification. MALDI‐TOF mass spectrometry may be used for confirmation, and whole genome sequencing may provide additional information on possible transmission events. Health care facilities must ensure processes are implemented for screening of patients who have received health care in overseas hospitals. Box – Comparison of clinical and epidemiological characteristics of Candida albicans and Candida auris Candida albicans Candida auris Colonisation Colonisation of patients in community and health care settings is common; a commensal of skin and gut of immunocompetent and immunocompromised hosts Colonisation of patients associated only with hospital outbreaks or transmission, also identified in environment and equipment in hospital outbreak settings Infection Infection most frequently at mucosal sites (eg, oropharyngeal, vulvovaginal); bloodstream and urinary tract infections less frequent Bloodstream, urinary tract and wound infections reported Risks for infection ICU or HDU admission, invasive medical devices, major abdominal surgery, solid tumours, haematological malignancies, broad spectrum antibiotics ICU or HDU admission, invasive medical devices, underlying immunocompromise or chronic disease (eg, diabetes, chronic lung disease, renal failure, cardiovascular disease, or malignancy), broad spectrum antibiotics or antifungal agents Geographical distribution Ubiquitous, community and health care settings Reported only in health care settings, expanding global distribution Laboratory identification Culture using selective chromogenic media Culture together with MALDI‐TOF or DNA sequencing Antifungal resistance Generally susceptible to fluconazole Resistance to fluconazole is likely* HDU = high dependency unit; ICU = intensive care unit; MALDI‐TOF = matrix‐assisted laser desorption ionisation time‐of‐flight mass spectrometry. *Note: agreed fluconazole minimum inhibitory concentration breakpoints for C. auris have not been established

Leon J Worth · Simon J Harrison · Michael Dickinson · Annaliese Diemen · Jennifer Breen · Susan Harper · Caroline Marshall · Deborah A Williamson · Karin A Thursky · Monica A Slavin

Mja2 50612
Environmental health Medical education 4 May 2020 Free

A case of toxigenic, pharyngeal diphtheria in Australia

Clinical record A 42‐year‐old woman presented to the Sunshine Coast University Hospital, Queensland, with a 5‐day history of odynophagia, orthopnoea and rapid onset of neck swelling over 12 hours. She had returned one week prior from a year‐long trip to Central America, Sri Lanka and Indonesia. Relevant past medical history included nephrotic syndrome due to minimal change disease, use of prednisolone 2.5 mg daily and previous treatment with rituximab. Childhood vaccinations were reported, but she had no booster travel vaccinations. On examination, she had right‐sided neck swelling, consistent with “bull neck” (Box, A), and an exudative right tonsil with a haemorrhagic component (Box, B). The patient had several healed skin lesions and a 2 cm non‐healing ulcer on her buttock. Flexible nasendoscopy showed supraglottic oedema with a patent airway. The diagnosis of diphtheria was strongly considered, with differentials including peritonsillar abscess and tonsillitis. Computed tomography scan of the neck demonstrated peritonsillar phlegmon and oedema in the parapharyngeal space, pre‐vertebral fat and subcutaneous neck tissues. She was commenced on intravenous benzylpenicillin, lincomycin and dexamethasone, was placed on contact and droplet precautions, and was admitted to the intensive care unit. Multiple tissue and swab samples were taken from the pharyngeal membrane and the buttock wound and urgently sent to the laboratory for culture into selective media. She underwent elective intubation 24 hours later due to worsening laryngeal oedema. Tissue and swabs from the pharyngeal membrane and sacral wound grew Corynebacterium diphtheriae. Diphtheria antitoxin (DAT) 100 000 IU was administered 36 hours into her admission. The isolates were confirmed to be toxigenic by polymerase chain reaction.1,2 The patient was discharged from the intensive care unit on Day 6. On Day 7, she developed anterior T wave inversions on her electrocardiogram, with an elevated troponin value (0.39 μg/L; reference range, < 0.040 μg/L). Her cardiac enzymes showed serial improvement. She developed a moderate glossopharyngeal and vagal palsy, which resolved after 3 weeks, and peripheral neuropathy, which resolved after 4 months. The cardiac and neurological sequelae were thought to be complications of pharyngeal diphtheria. The local Public Health Unit and the infection management service identified 12 staff and seven close community contacts. All contacts had nasal and throat swabs taken, were treated with oral erythromycin and were vaccinated where appropriate.3 Staff were excluded from work until returning negative throat and nasal cultures at 48–72 hours. Discussion Diphtheria is an acute pharyngeal or cutaneous infection caused by toxigenic strains of C. diphtheriae — a gram‐positive, non‐motile, non‐encapsulated bacillus.4 The infection spreads by respiratory droplets or direct contact with nasopharyngeal secretions or skin lesions. The incubation period of diphtheria is commonly 2–5 days. Data from the World Health Organization show that diphtheria is endemic to South‐East Asia, including Indonesia, Malaysia and the Philippines.5 Our case illustrates the need for a thorough travel history and administration of timely antitoxin therapy in suspected diphtheria cases to limit diphtheria‐related neurological and cardiovascular consequences. Diphtheria is rare in Australia after the widespread use of the effective vaccine following World War II, with most cases associated with sporadic importations. There have been seven cases of diphtheria reported since 2001, including one that was fatal in 2011.6 Diphtheria affects the upper respiratory tract, presenting with sore throat and cervical lymphadenopathy; a coating membrane forms in about a third of cases. Simultaneous infection of the skin and respiratory tract is uncommon. Accumulation of the C. diphtheriae organism within the membrane along with fibrin debris result in the appearance of a white pseudomembrane.4 The pathognomonic bull neck is caused by superficial oedema of neck tissues and is associated with a more severe course and higher mortality. The diphtheria toxin is produced by toxigenic strains of the bacterium and affects the cardiovascular, renal and nervous systems via haematogenous spread. The toxin is bound on cell surface receptors and acts to arrest protein synthesis.7 Toxin‐producing infections have a mortality rate between 5% and 10%.8 Diphtheritic myocarditis occurs in 10–20% of patients with pharyngeal diphtheria manifesting as ST disturbance, corrected QT interval (QTc) prolongation, or heart block.9 Cardiac abnormalities are associated with extensive respiratory tract involvement and bull neck appearance as well as neurological sequelae, which occur in 75% of patients with severe respiratory disease.4 Cranial nerve neuropathy develops first; often presenting as swallowing difficulties and resulting in aspiration. DAT and antibiotics should be administered promptly upon clinical suspicion. Early administration of DAT reduces circulating toxin load and reduces clinical sequelae.3 Our patient received DAT at 36 hours, yet significant neurological sequelae were observed up to 4 months later. Penicillin and/or erythromycin are the antimicrobials of choice; however, resistance has been described.10 Lessons from practice Diphtheria should be suspected in patients presenting with pseudomembranous tonsillitis, significant neck swelling and relevant travel history. It is important for clinicians to liaise with their local laboratory and Public Health Unit in suspicious cases so appropriate investigations and follow‐up can be established. Timely administration of diphtheria antitoxin is imperative and should not be delayed awaiting laboratory confirmation. Booster vaccinations should be considered before travel, particularly in patients who may have waning immunity. Box – “Bull neck” characteristic of diffuse cervical lymphadenopathy with tracheal deviation (A). Pseudomembrane coating right tonsil, soft palate and uvula on presentation (B)

Sarah Grigg · David Hogan · F Shaun Hosein · Dean Johns · Amy Jennison · Shradha Subedi

Mja2 50566
Infectious diseases Medical education 27 April 2020 Free

Necrotising enterocolitis caused by Clostridium perfringens: a life‐threatening manifestation of a common foodborne infection

Clinical record A 40‐year‐old woman of Karen ethnicity presented with 5 days of generalised abdominal pain. The pain was worsening and associated with vomiting in the 12 hours preceding presentation. She had been constipated for 5 weeks. There was no diarrhoea, no blood or mucous in the stool and no haematemesis. There were no sick family, friends or colleagues and no recent travel. She had an omnivorous diet, which had not changed recently, and worked casually at a vegetable farm. In the emergency department, vital signs were normal and the abdomen was mildly distended and tender. Initial blood tests showed a neutrophil count of 9.6 × 109/L (reference range [RR], 2.0–8.0 × 109/L), serum bicarbonate 22 mmol/L (RR, 22–32 mmol/L), normal renal function, and C‐reactive protein below 2.9 mg/L (RR, < 3.0 mg/L). Computed tomography of the abdomen and pelvis was consistent with colitis of the descending colon and ileus (Box 1). She was admitted for observation under the general surgical team. Five hours after admission, her condition rapidly deteriorated. Blood pressure was 80/40 mmHg, heart rate 129 beats per minute in sinus rhythm, and there was severe abdominal tenderness with generalised guarding. Repeat tests showed serum creatinine 175 μmol/L (RR, 60–110 μmol/L), bicarbonate below 10 mmol/L (RR, 22–32 mmol/L), blood pH 6.97 (RR, 7.35–7.45), and lactate 14.8 mmol/L (RR, < 1.5 mmol/L). At emergency surgery, colonoscopy and ileoscopy revealed mucosal inflammation affecting the distal 20 cm of terminal ileum, caecum, transverse and sigmoid colon, with patches of frank mucosal necrosis (Box 2). The bowel was grossly dilated, with small patches of full thickness caecal necrosis but no perforation. Subtotal colectomy, terminal ileectomy, and formation of an end ileostomy were performed, with resultant resolution of circulatory shock. Pathological examination demonstrated severe acute pancolitis and extensive mucosal necrosis (Box 3). Clostridium perfringens infection was suspected, due to a striking similarity to published cases.1,2C. perfringens was isolated from biopsy specimens of the necrotic colonic mucosa using selective culture media. The isolate expressed C. perfringens enterotoxin and α‐toxin, defined as toxinotype F.3 Postoperative management included vancomycin both orally and per rectum. Three months after the operation, she was pain‐free, with a normal appetite and functional state. Reversal of ileostomy is planned in coming months. Discussion C. perfringens is a gram‐positive bacillus that forms hardy spores, is ubiquitous in environmental soil and water, and can be part of normal bowel flora. Toxigenic strains commonly cause both foodborne and sporadic cases of acute, self‐limiting diarrhoea. The typical foodborne strain F produces C. perfringens enterotoxin and α‐toxin and was found in our patient.3 The organism exhibits the shortest known doubling time of any cell when grown at 42°C in cooked minced beef.4 Exposure to large inocula of toxigenic organisms may arise when meat is kept lukewarm before consumption. Enteric infections are characterised by adherence of organisms to small bowel mucosa before concurrent sporulation and release of toxin. This typically induces self‐limiting diarrhoea 10–12 hours after eating. Necrotising enterocolitis is a manifestation of C. perfringens enteric infection that is rare in high income countries. Some reported cases associate the condition with constipation, either pre‐existing due to medication side effects or induced by the high protein content of ingested contaminated meat. Constipation has been proposed to impair the usual expulsion of C. perfringens bacteria and spores, leading to mucosal necrosis and shock as opposed to the usual syndrome of transient diarrhoea. Mortality in case series is greater than 50%.1,2 Despite thorough assessment, the cause of our patient's constipation and means of exposure remain unclear. She most likely contracted the infection hours before the onset of her pain, 5 days before presentation. Exposure could have occurred during food preparation at home, meals with social groups, or via soil at her workplace. While rare in Australia, a type of C. perfringens necrotising enteritis was endemic throughout the 20th century in the Papua New Guinea highlands, caused by β‐toxin‐producing strains. Called “pigbel” in Tok Pisin, the disease is closely associated with traditional pig feasts. In the 1960s and 1970s, pigbel accounted for almost a quarter of paediatric deaths in highlands hospitals. Implementation of a β‐toxoid vaccine in 1979 resulted in an eightfold reduction in incidence and an even greater reduction in disease‐specific mortality.5 C. perfringens infection is an important differential diagnosis in cases of acute severe enteritis or colitis, particularly if accompanied by circulatory shock. Prompt operative intervention is necessary in such situations. In Papua New Guinea, toxoid vaccination has proven very successful. In Australia, food safety practices likely play the greatest role in controlling disease burden. Lessons from practice Toxigenic Clostridium perfringens type F commonly causes acute diarrhoea, with illness typically commencing hours after meat consumption. Cases are usually self‐limiting, and require symptomatic management only. Very rarely, toxigenic C. perfringens strains can cause fulminant bowel necrosis requiring emergency bowel resection, which may be associated with pre‐existing constipation. In the highlands of Papua New Guinea, necrotising enteritis has been a common cause of paediatric morbidity and mortality, where it is caused by a locally endemic strain of toxigenic C. perfringens. Box 1 – Coronal computed tomography image of the abdomen and pelvis with portal venous phase contrast, demonstrating mural thickening of the descending colon in the left lower quadrant and fluid‐filled distension of the transverse colon, ascending colon, and ileum Box 2 – Endoscopy images obtained immediately before laparotomy, showing mucosal necrosis of the ascending colon Box 3 – Macroscopic appearance of resected colon, demonstrating extensive mucosal necrosis and oedema

Harry N Walker · Kwee‐Chin Liew · Vicki Adams · Sarah Larcombe · Sonal S Nagra · Glenn Guest · Eugene Athan

Mja2 50568

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