Developing core elements and checklist items for global hospital antimicrobial stewardship programmes: a consensus approach.

OBJECTIVES: With increasing global interest in hospital antimicrobial stewardship (AMS) programmes, there is a strong demand for core elements of AMS to be clearly defined on the basis of principles of effectiveness and affordability. To date, efforts to identify such core elements have been limited to Europe, Australia, and North America. The aim of this study was to develop a set of core elements and their related checklist items for AMS programmes that should be present in all hospitals worldwide, regardless of resource availability. METHODS: A literature review was performed by searching Medline and relevant websites to retrieve a list of core elements and items that could have global relevance. These core elements and items were evaluated by an international group of AMS experts using a structured modified Delphi consensus procedure, using two-phased online in-depth questionnaires. RESULTS: The literature review identified seven core elements and their related 29 checklist items from 48 references. Fifteen experts from 13 countries in six continents participated in the consensus procedure. Ultimately, all seven core elements were retained, as well as 28 of the initial checklist items plus one that was newly suggested, all with ≥80% agreement; 20 elements and items were rephrased. CONCLUSIONS: This consensus on core elements for hospital AMS programmes is relevant to both high- and low-to-middle-income countries and could facilitate the development of national AMS stewardship guidelines and adoption by healthcare settings worldwide.

Antibiotic stewardship in low- and middle-income countries: the same but different?

BACKGROUND: Antibiotic resistance (ABR) is a quickly worsening problem worldwide, also in low- and middle-income countries (LMICs). Appropriate antibiotic use in humans and animals, i.e. antibiotic stewardship (ABS), is one of the cornerstones of the World Health Organization's global action plan for ABR. Many LMICs are in the process of developing stewardship programs. AIMS: We highlight challenges for ABS initiatives in LMICs, give an outline of (inter)national recommendations and demonstrate examples of effective, contextualized stewardship interventions. SOURCES: We searched PubMed for articles on ABS interventions in humans in LMICs. Relevant websites and experts were consulted for additional sources. CONTENT: Evidence on effective and feasible stewardship interventions in LMICs is limited, and challenges for implementation of interventions are numerous. Nevertheless, several initiatives at the international and local levels in Latin America, Africa and Asia have shown that ABS effective interventions are feasible in LMICs, although contextualization is essential. IMPLICATIONS: Specific guidance for setting up antimicrobial stewardship programs in LMICs should be developed. Strategic points might need to be progressively addressed in LMICs, such as (a) ensuring availability of diagnostic testing, (b) providing dedicated education in ABR both for healthcare workers and the general public, (c) creating or strengthening (inter)national agencies towards better regulations and audit on production, distribution and dispensing of drugs, (d) strengthening healthcare facilities, (e) exploring a broader synergism between policy makers, academia, professional bodies and civil society and (f) designing and studying easy and scalable ABS interventions for both hospital and community settings.

Antibiotic susceptibility profiles among Campylobacter isolates obtained from international travelers between 2007 and 2014.

Campylobacter infection is a common cause of diarrhea among international travelers. We studied antibiotic resistance patterns among Campylobacter isolates obtained from international travelers according to travel destination. Three collections of isolates obtained from international travelers between 2007 and 2014 (Institute of Tropical Medicine, the "Laboratoire Hospitalier Universitaire de Bruxelles "and the Belgian National Reference Centre for Campylobacter) were used. Isolates were tested for minimal inhibitory concentration (MIC) values (E-test macromethod) for fluoroquinolones, macrolides, tetracyclines, amoxicillin-clavulanic acid, and meropenem. Single isolates from 261 travelers were available; median (IQR) age was 25.4 (4-42) years, 85.8% were symptomatic (information for 224 patients available). Overall resistance to ciprofloxacin was 60.9%, ranging from 50.8% in Africa to 75.0% in Asia. Resistance to erythromycin was 4.6%, with the highest rate observed for Southern Asia (15.2%, seven isolates, six of them recovered from patients returning from India). A total of 126 isolates (48.3%) were resistant to tetracycline. No resistance to amoxicillin-clavulanic acid or meropenem was detected. Ciprofloxacin resistance tended to increase over time (53.9% in 2007 versus 72.2% in 2014), erythromycin resistance remained stable (median annual resistance 4.2%). Most (86.2%) ciprofloxacin-resistant isolates had MIC values ≥32 mg/l, and all erythromycin-resistant isolates had MIC values ≥256 mg/l. Co-resistance to ciprofloxacin and erythromycin was observed in 11 (4.2%) isolates, seven of which came from Southern Asia. Among all regions of travel, more than half of Campylobacter isolates were resistant to ciprofloxacin. Overall resistance to erythromycin was below 5% but reached 15.2% in Southern Asia.

Prevalence and distribution of beta-lactamase coding genes in third-generation cephalosporin-resistant Enterobacteriaceae from bloodstream infections in Cambodia.

Resistance to third-generation cephalosporins in Gram-negative bacteria is emerging in Asia. We report the prevalence and distribution of extended-spectrum beta-lactamase (ESBL), AmpC beta-lactamase and carbapenemase-coding genes in cefotaxime-resistant Enterobacteriaceae isolates from bloodstream infections (BSI) in Cambodia. All Enterobacteriaceae isolated from BSI in adult patients at Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia (2007-2010) were assessed. Antimicrobial susceptibility testing was carried out by disc diffusion and MicroScan according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Screening for ESBL, plasmidic AmpC and carbapenemase-coding genes was performed by multiplex polymerase chain reaction (PCR) sequencing assays. Identification of the ST131 clone was performed in all CTX-M-positive Escherichia coli, using PCR targeting the papB gene. Out of 183 Enterobacteriaceae, 91 (49.7 %) isolates (84 BSI episodes) were cefotaxime-resistant: E. coli (n = 68), Klebsiella pneumoniae (n = 17) and Enterobacter spp. (n = 6). Most episodes were community-acquired (66/84; 78.3 %). ESBLs were present in 89/91 (97.8 %) cefotaxime-resistant isolates: 86 (96.6 %) were CTX-M, mainly CTX-M-15 (n = 41) and CTX-M-14 (n = 21). CTX-M of group 1 were frequently associated with TEM and/or OXA-1/30 coding genes and with phenotypic combined resistance to ciprofloxacin, sulphamethoxazole-trimethoprim and gentamicin (39/50, 78.0 %). Plasmidic AmpC (CMY-2 and DHA-1 types) were found alone (n = 2) or in combination with ESBL (n = 4). Eighteen E. coli isolates were identified as B2-ST131-O25B: 11 (61.1 %) carried CTX-M-14. No carbapenemase-coding genes were detected. ESBL among Enterobacteriaceae from BSI in Cambodia is common, mainly associated with CTX-M-15 and CTX-M-14. These findings warrant urgent action for the containment of antibiotic resistance in Cambodia.

Increase in Salmonella enterica serovar Paratyphi A infections in Phnom Penh, Cambodia, January 2011 to August 2013.

We report an increased number of Salmonella enterica Paratyphi A infections in adults in Cambodia. Between January 2011 and August 2013, 71 S. Paratyphi A isolates were recovered from blood cultures, representing a 44-fold increase compared to July 2007 to December 2010, while monthly numbers of cultures did not change. Infections with S. Typhi increased two-fold in the same period. Most cases came from the capital Phnom Penh. These findings warrant epidemiological investigation to support public health measures.

Outbreak of Burkholderia cepacia bloodstream infections traced to the use of Ringer lactate solution as multiple-dose vial for catheter flushing, Phnom Penh, Cambodia.

The Burkholderia cepacia complex is a group of Gram-negative bacteria known as respiratory pathogens in cystic fibrosis patients, but also increasingly reported as a cause of healthcare associated infections. We describe an outbreak of B. cepacia bloodstream infections in a referral hospital in Phnom Penh, Cambodia. Over a 1.5-month period, blood cultures from eight adult patients grew B. cepacia. Bloodstream infection occurred after a median of 2.5 days of hospitalisation. Three patients died: 7, 10 and 17 days after blood cultures were sampled. As part of the outbreak investigation, patient files were reviewed and environmental sampling was performed. All patients had peripheral venous catheters that were flushed with Ringer lactate drawn from a 1 L bag, used as multiple-dose vial at the ward. Cultures of unopened Ringer lactate and disinfectants remained sterile but an in-use bag of Ringer lactate solution and the dispensing pin grew B. cepacia. The isolates from patients and flushing solution were identified as B. cepacia by recA gene sequence analysis, and random amplified polymorphic DNA typing confirmed clonal relatedness. The onset of the outbreak had coincided with the introduction of a dispensing pin with a screw fit that did not allow proper disinfection. Re-enforcement of aseptic procedures with sterile syringe and needle has ended the outbreak. Growth of B. cepacia should alert the possibility of healthcare associated infection also in tropical resource-limited settings. The use of multiple-dose vials should be avoided and newly introduced procedures should be assessed for infection control risks.

First National Workshop on Antibiotic Resistance in Cambodia: Phnom Penh, Cambodia, 16-18 November 2011.

The First National Workshop on Antibiotic Resistance in Cambodia was organised by the Cambodian Ministry of Health with support from several national and international partner institutions. It brought together policy-makers, clinicians, pharmacists, laboratory technicians and other professionals dealing with the problems of bacterial infection and antibiotic resistance across the country. Antibiotic resistance data from starting up and experienced laboratories were presented, showing high rates of resistance in key pathogens to most antibiotics currently available in Cambodia, e.g. 70-90% multidrug resistance and 70-80% decreased ciprofloxacin susceptibility in Salmonella enterica serovar Typhi, 20-40% meticillin resistance rates in Staphylococcus aureus and 30-50% extended-spectrum ß-lactamase production in Escherichia coli. A five-point plan was discussed, which included initiatives from government and non-governmental partners, focusing on rational prescribing, clinical practice guidelines, improved laboratory services, infection prevention and enhanced education at all levels. Implementation, however challenging, is a priority given the high levels of resistance seen in key pathogens and the overall health needs in the country.

The immune reconstitution inflammatory syndrome: a cause of death in persons on antiretroviral therapy?

The availability of antiretroviral therapy (ART) has significantly improved the quality of life of persons with HIV infection. However, new problems have arisen as a consequence of this treatment. An immune reconstitution inflammatory syndrome (IRIS) in which patients experience a paradoxical worsening of their clinical condition may occur during recovery of the immunity. Thus far, there is no laboratory test available to diagnose IRIS. The diagnosis therefore remains clinical and by exclusion. In this paper, we describe the autopsy findings of three HIV-infected patients who died at the Antwerp University hospital directly or indirectly related to IRIS. One patient died following a disseminated cryptococcocal and Mycobacterium avium complex (MAC) infection. Two other patients died with a disseminated aspergillosis infection after receiving corticosteroids to decrease IRIS induced inflammatory signs. These three patients show the difficulties faced by clinicians in diagnosing IRIS and the importance of performing autopsies in persons with HIV infection who die despite receiving ART.

A tropical diabetic foot.

Foot infections are a common problem and an important cause of morbidity in patients with diabetes. We report a patient with type 2 diabetes, presenting with a chronic foot wound resistant to standard care, in whom the diagnosis of eumycetoma was made through histopathological examination of a bone biopsy specimen and confirmed by polymerase chain reaction (PCR). Diagnosis and treatment of eumycetoma are reviewed. Eumycetoma caused by Madurella mycetomatis is an uncommon cause of osteomyelitis in patients with diabetes in Europe, but should be considered in patients from endemic regions when (antibacterial) therapy fails.

Inhaled corticosteroids in persons with HIV infection: not that harmless.

There is a growing group of HIV-seropositive patients at risk for chronic lung disease due to their life style and age. The interaction between certain antiretroviral drugs and corticosteroid inhalation therapy is potentially dangerous but often unrecognised. We present three cases from our HIV-clinic of whom two developed full blown Cushing's syndrome over a short period of time and one presented with asymptomatic hypocortisolaemia due to serious drug interactions between HIV-drugs and inhaled corticosteroids. General practitioners, HIV and chest physicians should all be aware of this potentially life-threatening interaction and the combination of those products should be avoided where possible.

Human African trypanosomiasis in a Belgian traveller returning from the Masai Mara area, Kenya, February 2012.

A Belgian traveller was diagnosed with human African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense nine days after visiting the Masai Mara area in Kenya. He presented with an inoculation chancre and was treated with suramin within four days of fever onset. Two weeks earlier, HAT was also reported in a German traveller who had visited the Masai Mara area. Because no cases have occurred in the area for over 12 years, this may indicate a focal cluster of HAT.

Epidemiology and outcome of Shigella, Salmonella and Campylobacter infections in travellers returning from the tropics with fever and diarrhoea.

INTRODUCTION: During a study on fever after a stay in the tropics, we aimed at investigating the epidemiology and outcome of invasive bacterial enteritis due to Shigella, Salmonella or Campylobacter spp. in patients diagnosed with febrile traveller's diarrhoea. METHODS: From April 2000 to September 2006, we evaluated prospectively 594 travellers presenting with fever and diarrhoea within a month after a stay in the tropics. Patients not found with a systemic infection were assumed to have febrile traveller's diarrhoea (TD). Invasive bacterial enteritis was confirmed by isolation of Shigella, Campylobacter or nontyphoidal Salmonella in stool cultures. RESULTS: Systemic infections (mainly malaria) were diagnosed in 259 (44%) evaluated travellers. Invasive bacterial enteritis, either alone or with another infection, was confirmed in 114 (34%) of the 335 remaining patients with febrile TD. Aetiologies were distributed between Campylobacter jejuni (47, 41%), Shigella spp. (43, 38%), Salmonella spp. (22, 19%) and mixed Campylobacter-Salmonella infection (2, 2%). Invasive bacterial enteritis accounted for about a third of febrile TD cases occurring after a stay in sub-Saharan Africa, North Africa/Middle East or Latin America, and for half of those occurring after a travel to southern Asia (including 33% only due to C. jejuni). Resistance to fluoroquinolones was exclusively observed in C. jejuni isolates, but at an overall rate of 53%. Clinical failure occurred in 33% of the patients with C. jejuni infection empirically treated with a fluoroquinolone. CONCLUSION: Invasive bacterial enteritis was a frequent aetiology of febrile TD. C. jejuni was the leading pathogen after a travel to southern Asia, and was associated with high rate of resistance to fluoroquinolones and of clinical failure.

Medical and surgical management of paraneoplastic pyoderma gangrenosum--a case report and review of the literature.

We present a case of a 44-year-old male with pyoderma gangrenosum (PG) presenting simultaneously with diagnosis of acute leukemia. His skin disease was stabilized with corticosteroids and most lesions cleared after chemotherapy-induced remission of the malignancy, but the largest lesion remained necrotic. Surgical treatment of the large necrotic ulcer included debridement followed by split-thickness skin graft while maintaining corticoid therapy. Unfortunately, relapse of the pyoderma gangrenosum with bullous lesions heralded relapse of the ultimately fatal malignancy. This case illustrates: (1) PG presenting simultaneously with a haematologic malignancy (2) Relapse with atypical bullous lesions with return of the malignancy and (3) The use of surgical modalities in managing patients with PG, a disease notorious for surgical complications.

Evaluation of the Immunoquick+4 malaria rapid diagnostic test in a non-endemic setting.

The aim of this retrospective study was to evaluate the Immunoquick+4 (BioSynex, Strasbourg, France), a three-band malaria rapid diagnostic test (MRDT) targeting histidine-rich protein-2 (HRP-2) and pan Plasmodium-specific parasite lactate dehydrogenase, in a non-endemic reference setting. Stored whole-blood samples (n = 613) from international travellers suspected of malaria were used, with microscopy corrected by polymerase chain reaction (PCR) as the reference method. Samples infected by P. falciparum (n = 323), P. vivax (n = 97), P. ovale (n = 73) and P. malariae (n = 25) were selected, as well as 95 malaria-negative samples. The overall sensitivities of the Immunoquick+4 for the diagnosis of P. falciparum, P. vivax, P. malariae and P. ovale were 88.9, 75.3, 56.0 and 19.2%, respectively. Sensitivity was significantly related to parasite density for P. falciparum (93.6% versus 71.4% at parasite densities >100/microl and 500/microl and

[Non-tuberculous mycobacterial infections of the hand and wrist: a retrospective review of five cases from a single centre]. / Nicht-tuberkulöse mykobakterielle Infektionen an Hand und Handgelenk: Eine retrospektive Analyse von fünf Fällen.

PURPOSE: A suggestion for a graduated diagnostic and therapeutic approach for patients with a suspected infection with non-tuberculous mycobacteria (NTM) of the hand and wrist is made. PATIENTS AND METHODS: Between March 2003 and February 2007, 2 women and 3 men with an average age of 64 years were treated for an NTM infection of the hand and wrist. 4 patients had a tenosynovitis of the wrist. In 1 patient both wrists were involved. 1 patient had a granuloma of the index finger. The patients' charts, the operation reports, histological and bacteriological findings and the antibiogram were evaluated. RESULTS: An inoculating trauma was identified in four patients. Intraoperatively rice bodies were present in the 4 patients with a tenosynovitis of the wrist. Histological findings showed acid-fast bacilli in 2 patients and chronic inflammatory reaction with/without granuloma (3/2) in 5 patients. Species identification was based on PCR and microbiological culture and revealed in three patients slow growing species (M. malmoense, M. nonchromogenicum, M. szulgai) and in two patients M. marinum (intermediate growth rate). Therapy consisted of immediate postoperative empirical combined drug treatment followed by antibiogram-based therapy. All patients showed healing of the infection at the final follow-up at an average of 25.2 months (range: 15-44 months) postoperatively. CONCLUSION: Consideration of non-tuberculous mycobacteria in the differential diagnosis in cases of localised tenosynovitis is paramount for diagnosis. Treatment based on graduated diagnostic steps, surgery and drugs (empirical followed by directed drugs) can achieve favourable clinical outcomes.

A traveler with neurobrucellosis.

An Indian traveler developed fever and neurological symptoms after a visit to East Africa. He was treated with suramin, melarsoprol and prednisolone for presumed East African trypanosomiasis. His condition deteriorated and cerebral lesions developed. Neurobrucellosis was diagnosed. Combination antibiotic therapy led to gradual clinical improvement and regression of the brain lesions. Misdiagnosis of East African trypanosomiasis followed by treatment with potentially lethal medication should be avoided by not relying on insufficient evidence during the diagnostic process.

Antibiotic resistance among bacterial pathogens in Central Africa: a review of the published literature between 1955 and 2008.

A systematic review of the published literature on bacterial resistance in Central Africa between 1955 and 2008 was performed. Eighty-three publications from seven countries were retrieved, the majority presenting data on enteric and other gram-negative pathogens. Despite methodological limitations in many studies, alarming resistance rates are noted in nearly all pathogens. Of special concern are multidrug resistance in Shigella and Salmonella spp. and the emergence of meticillin-resistant Staphylococcus aureus, high-level penicillin-resistant Streptococcus pneumoniae and extended-spectrum beta-lactamases among gram-negative pathogens. These findings make clear that the Central African region shares the worldwide trend of increasing antimicrobial resistance and is in urgent need of sound surveillance based on competent and affordable microbiology to provide clear data on antimicrobial resistance. These data could enable redaction of local treatment guidelines and fuel national and regional policies to contain antimicrobial resistance.

A frontal mucocele caused by an immune reconstitution inflammatory syndrome in a patient with HIV infection.

We describe a 55-year-old bisexual Belgian man with a multi-drug resistant HIV infection who developed an Immune Reconstitution Inflammatory Syndrome (IRIS) presenting as a mucocele of the frontal sinus, one year after starting a new effective darunavir containing antiretroviral treatment regimen. His CD4+ lymphocyte count had increased from 3 cells/mm3 prior to the start of the latter treatment to 196 cells/mm3 just before he developed the IRIS phenomenon. IRIS is a paradoxical clinical deterioration during highly active antiretroviral treatment (HAART), due to an exaggerated immune-inflammatory reaction. With the increasing numbers of persons living with HIV infection and the increased use of HAART it is expected that in the future more otolaryngological manifestations of IRIS will be detected.