Broad-spectrum Antimicrobial Treatment Research Articles

A pilot study investigating severe community-acquired febrile illness through implementation of an innovative microbiological and nucleic acid amplification testing strategy in Timor-Leste (ISIN-MANAS-TL)

ObjectivesAcute febrile illness (AFI) causes significant health-seeking, morbidity, and mortality in Southeast Asia. This pilot study aimed to describe presentation, etiology, treatment, and outcomes of patients with AFI at one hospital in Timor-Leste and assessing the feasibility of conducting larger studies in this setting. MethodsPatients attending Hospital Nacional Guido Valadares with tympanic or axillary temperature ≥37.5°C in whom a blood culture was taken as part of routine clinical care were eligible. Participants were followed up daily for 10 days and again after 30 days. Whole blood was analyzed using a real-time quantitative polymerase chain reaction assay detecting dengue virus serotypes 1-4 and other arthropod-borne infections. ResultsA total of 82 participants were recruited. Polymerase chain reaction testing was positive for dengue in 14 of 82 (17.1%) participants and blood culture identified a bacterial pathogen in three of 82 (3.7%) participants. Follow-up was completed by 75 of 82 (91.5%) participants. High rates of hospital admission (58 of 82, 70.7%), broad-spectrum antimicrobial treatment (34 of 82, 41.5%), and mortality (9 of 82, 11.0%) were observed. ConclusionsPatients with AFI experience poor clinical outcomes. Prospective observational and interventional studies assessing interventions, such as enhanced diagnostic testing, clinical decision support tools, or antimicrobial stewardship interventions, are required and would be feasible to conduct in this setting.

Heartland Virus Disease-An Underreported Emerging Infection.

First recognized 15 years ago, Heartland virus disease (Heartland) is a tickborne infection contracted from the transmission of Heartland virus (HRTV) through tick bites from the lone star tick (Amblyomma americanum) and potentially other tick species. Heartland symptoms include a fever <100.4 °F, lethargy, fatigue, headaches, myalgia, a loss of appetite, nausea, diarrhea, weight loss, arthralgia, leukopenia and thrombocytopenia. We reviewed the existing peer-reviewed literature for HRTV and Heartland to more completely characterize this rarely reported, recently discovered illness. The absence of ongoing serosurveys and targeted clinical and tickborne virus investigations specific to HRTV presence and Heartland likely contributes to infection underestimation. While HRTV transmission occurs in southern and midwestern states, the true range of this infection is likely larger than now understood. The disease's proliferation benefits from an expanded tick range due to rising climate temperatures favoring habitat expansion. We recommend HRTV disease be considered in the differential diagnosis for patients with a reported exposure to ticks in areas where HRTV has been previously identified. HRTV testing should be considered early for those matching the Heartland disease profile and nonresponsive to initial broad-spectrum antimicrobial treatment. Despite aggressive supportive therapy, patients deteriorating to sepsis early in the course of the disease have a very grim prognosis.

Neonatal Intraventricular Hemorrhage Presenting as Pyrexia of Newborn: A Case Report

Abstract: &#x0D; Background Temperature instability is a relatively common presenting symptom in a Neonatal Intensive Care Unit (NICU) with sepsis being one of the major etiologies that need to be ruled out. However, an important differential diagnosis is a central fever. Many cases of Intracranial Hemorrhage/Intraventricular Hemorrhage (ICH/IVH) present with temperature dysregulation with no other clear associated symptoms, and cranial imaging for early identification and treatment of ICH/IVH is crucial. &#x0D; Case report A 3-day-old male born at 33 weeks and four days of gestation who was admitted to the neonatal critical care unit due to prematurity and respiratory distress was noted to be febrile during the fourth hospital day. The septic screen was negative, and the patient continued to spike fever while on broad-spectrum antimicrobial treatment. Due to an unexplained drop in his hematocrit, cranial ultrasound was done, and grade III IVH was identified. The patient continued to improve clinically, but the exact etiology of his IVH was not identified. His fever resolved without interventions, and his IVH continued to decrease in size. Serial cranial imaging was done in NICU, and no neurosurgical interventions were warranted. He was referred to neurosurgery and neurology and followed in the infant’s high-risk clinic. &#x0D; Discussion Sepsis is the top of differentials when managing a newborn infant in NICU. However, we must always keep our minds open to other differentials, including central hyperthermia. Extreme prematurity is a major risk factor for ICH/IVH in the neonatal period; nonetheless, other risk factors are identified, and many cases of ICH/IVH had no identified causative factor or even risk factors. &#x0D; Conclusion Identifying clinical presentation and risk factors associated with ICH and IVH in NICU patients is crucial for early diagnosis and offers appropriate management. A high index of suspicion is required to promptly diagnose ICH/IVH resulting in central fever and avoid unnecessary workup and treatment.

Successful Extracorporeal Blood Purification Therapy using Double Haemoadsorption Device in Severe Endotoxin Septic Shock: A Case Report.

In patients admitted to the Intensive Care Unit (ICU), sepsis can lead to acute kidney injury (AKI), which may require the initiation of continuous renal replacement therapy (CRRT) in 15-20% of cases. There is no consensus about the best extracorporeal treatment to choose in septic patients with AKI. We describe the case of a 70-year-old woman admitted to the ICU with a severe endotoxin septic shock due to Neisseria meningitidis serogroup C. Despite prompt medical intervention, including fluid resuscitation, high dose vasopressor, inotrope support, and broad-spectrum antimicrobial treatment, in a few hours patient's haemodynamic worsened and she developed multi-organ failure, including severe AKI, requiring CRRT. So, continuous veno-venous haemodiafiltration was started, using an oXiris® haemodiafilter set, in series with an adsorber device (CytoSorb®). After 48 hours of this combined extracorporeal treatment, haemodynamic parameters improved, allowing a significant reduction of the vasoactive therapy, with a concomitant decrease in endotoxin and inflammatory markers serum levels. In the following days patient's conditions still improved and renal function recovered. Timely extracorporeal blood purification therapy, using a double haemoadsorption device, may be effective in the management of severe septic shock.

Antimicrobial Efficacy of an Ultraviolet-C Device against Microorganisms Related to Contact Lens Adverse Events.

The purpose of the study was to assess the antimicrobial activity of an ultraviolet-C (UVC) device against microorganisms implicated in contact lens related adverse events. An UVC device with an emitting 4.5 mm diameter Light Emitting Diode (LED; 265 nm; 1.93 mJ/cm2) was used. Pseudomonas aeruginosa, Staphylococcus aureus, Fusarium solani, and Candida albicans agar plate lawns were exposed to the device beams for 15 and 30 s at 8 mm distance. Following the exposure, the diameter of the growth inhibition zone was recorded. Contact lenses made of Delfilicon-A, Senofilicon-A, Comfilicon-A, Balafilicon-A, Samfilicon-A and Omafilicon-A and a commercially available contact storage case was used. They were exposed to bacterial and fungal strains for 18 h at 37 °C and 25 °C respectively. After this, the samples were exposed to UVC for 30 s at 8 mm distance to determine the antimicrobial efficacy. Samples were then gently washed and plated on appropriate agar for enumeration of colonies. The UVC exposure reduced microbial growth by 100% in agar lawns, and significantly (p < 0.05) reduced microbial contamination to contact lenses and cases, ranging between 0.90 to 4.6 log. Very short UVC exposure has high antimicrobial efficacy against most of the predominant causative microorganisms implicated in contact lens related keratitis. UVC could be readily used as a broad-spectrum antimicrobial treatment for lens disinfection.

Case reports of invasive mucormycosis associated neutropenic enterocolitis in leukemic children: diagnostic and treatment challenges and review of literature

BackgroundBacterial enterocolitis is one of the most common neutropenic fever complications during intensive chemotherapy. Despite aggressive antibacterial treatments, this complication usually imposes high morbidity and mortality in cancer patients. Management of bacterial neutropenic enterocolitis are well known; however, management of fungal neutropenic enterocolitis may be more challenging and needs to be investigated. Prompt diagnosis and treatment may be life-saving, especially in patients at risk of mucormycosis-associated neutropenic enterocolitis.Case presentationWe report two mucormycosis-associated neutropenic enterocolitis cases in pediatric leukemic patients receiving salvage chemotherapy for disease relapse. Both patients' clinical signs and symptoms differ from classical bacterial neutropenic enterocolitis. They were empirically treated as bacterial neutropenic enterocolitis with anti-gram-negative combination therapy. Despite broad-spectrum antimicrobial treatment, no clinical improvement was achieved, and both of them were complicated with severe abdominal pain necessitating surgical intervention. Mucormycosis is diagnosed by immunohistopathologic examination in multiple intraoperative intestinal tissue biopsies. Both patients died despite antifungal treatment with liposomal amphotericin-B and surgical intervention.ConclusionMucormycosis-associated neutropenic enterocolitis is one of the most unfavorable and untreatable side effects of salvage chemotherapy in leukemic children with disease relapse. This report could be of considerable insight to the clinicians and scientists who counter the enigma of fungal infections during febrile neutropenia and help to understand better diagnosis and management.

A Biosynthesized Near-Infrared-Responsive Nanocomposite Biomaterial for Antimicrobial and Antibiofilm Treatment.

Photodynamic inactivation (PDI) has become an appealing alternative strategy to treat infections without developing resistance to microbes. In PDI treatment, near-infrared (NIR) light is preferred because it causes less damage to normal tissues and leads to better penetration in deep tissues. Here, we develop an NIR-responsive nanomedicine for efficient broad-spectrum antimicrobial photodynamic treatment. By harnessing the biosynthetic capability of a bacterial cellulose-producing microorganism, we construct a nanocomposite biomaterial to deliver and recycle the nanomedicine. Our simple one-step biosynthetic approach does not impede the antimicrobial potency of the nanomedicine under NIR activation and requires no chemical modification. The resulting nanocomposite has been tested in antimicrobial treatment of different microorganisms, exhibiting a great potential to eliminate pathogens in biofilms and to treat in vivo infections.

Post-keratoplasty Infectious Keratitis: Epidemiology, Risk Factors, Management, and Outcomes.

Post-keratoplasty infectious keratitis (PKIK) represents a unique clinical entity that often poses significant diagnostic and therapeutic challenges. It carries a high risk of serious complications such as graft rejection and failure, and less commonly endophthalmitis. Topical corticosteroids are often required to reduce the risk of graft rejection but their use in PKIK may act as a double-edged sword, particularly in fungal infection. The increased uptake in lamellar keratoplasty in the recent years has also led to complications such as graft-host interface infectious keratitis (IIK), which is particularly difficult to manage. The reported incidence of PKIK differs considerably across different countries, with a higher incidence observed in developing countries (9.2–11.9%) than developed countries (0.02–7.9%). Common risk factors for PKIK include the use of topical corticosteroids, suture-related problems, ocular surface diseases and previous corneal infection. PKIK after penetrating keratoplasty or (deep) anterior lamellar keratoplasty is most commonly caused by ocular surface commensals, particularly Gramme-positive bacteria, whereas PKIK after endothelial keratoplasty is usually caused by Candida spp. Empirical broad-spectrum antimicrobial treatment is the mainstay of treatment for both PKIK, though surgical interventions are required in medically refractory cases (during the acute phase) and those affected by visually significant scarring (during the late phase). In this paper, we aim to provide a comprehensive overview on PKIK, encompassing the epidemiology, risk factors, causes, management and outcomes, and to propose a treatment algorithm for systematically managing this challenging condition.

Amniotic membrane transplantation for infectious keratitis: a systematic review and meta-analysis

Infectious keratitis (IK) is the 5th leading cause of blindness globally. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though adjuvant treatment or surgeries are often required in refractory cases of IK. This systematic review aimed to examine the effectiveness and safety of adjuvant amniotic membrane transplantation (AMT) for treating IK. Electronic databases, including MEDLINE, EMBASE and Cochrane Central, were searched for relevant articles. All clinical studies, including randomized controlled trials (RCTs), non-randomized controlled studies and case series (n > 5), were included. Primary outcome measure was time to complete corneal healing and secondary outcome measures included corrected-distance-visual-acuity (CDVA), uncorrected-distance-visual-acuity (UDVA), corneal vascularization and adverse events. A total of twenty-eight studies (including four RCTs) with 861 eyes were included. When compared to standard antimicrobial treatment alone, adjuvant AMT resulted in shorter mean time to complete corneal healing (− 4.08 days; 95% CI − 6.27 to − 1.88; p < 0.001) and better UDVA (− 0.26 logMAR; − 0.50 to − 0.02; p = 0.04) at 1 month follow-up in moderate-to-severe bacterial and fungal keratitis, with no significant difference in the risk of adverse events (risk ratio 0.80; 0.46–1.38; p = 0.42). One RCT demonstrated that adjuvant AMT resulted in better CDVA and less corneal vascularization at 6 months follow-up (both p < 0.001). None of the RCTs examined the use of adjuvant AMT in herpetic or Acanthamoeba keratitis, though the benefit was supported by a number of case series. In conclusion, AMT serves as a useful adjuvant therapy in improving corneal healing and visual outcome in bacterial and fungal keratitis (low-quality evidence). Further adequately powered, high-quality RCTs are required to ascertain its therapeutic potential, particularly for herpetic and Acanthamoeba keratitis. Future standardization of the core outcome set in IK-related trials would be invaluable.

71 Electronic Prescribing Promotes Antimicrobial Stewardship In Surgery: A Closed-Loop Audit

Abstract Introduction Antimicrobial resistance is increasing globally. Surgical inpatients are more likely to receive inappropriately broad-spectrum and prolonged antimicrobial treatment, against local policy. Electronic prescribing (e-prescribing) has the potential to promote antimicrobial stewardship. We conducted a closed-loop audit to assess the impact of e-prescribing on surgical inpatient prescriptions. Method Audit standards (from Public Health England) included: (1) documentation of allergy status, prescriber contact information, antimicrobial indication and review/stop dates; and (2) prescription of appropriate antimicrobials for appropriate durations (IV and total). Prospective data collection occurred over 1-week. The interventions included an educational session, a once weekly microbiology round of surgical inpatients and the introduction of e-prescribing (Cerner©). Results Compliance improved significantly between cycle 1 (n = 54 prescriptions) and 2 (n = 59 prescriptions), for: documentation of prescriber contact details (69 vs 100%) and appropriate antimicrobial review/stop dates (17 vs 100%), indications (78 vs 96%), selection (76 vs 90%) and IV and total antibiotic duration (63 vs 93% and 87 vs 100%, respectively); p &amp;lt; 0.05 throughout. Conclusions Audit compliance improved significantly, partly because Cerner© prompts clinicians to input contact details, review dates and indications before prescribing. E-prescribing in combination with appropriate education is likely to promote antimicrobial stewardship and should be considered by other Trusts using paper prescriptions.

Efficacy and safety of antimicrobial de-escalation of treatment for sepsis: A protocol for systematic review and meta-analysis.

Background:Sepsis has become a global healthcare problem and continues to be one of the leading causes of death due to infection. In essence, early recognition and diagnosis of sepsis is needed to inhibit the transition into septic shock, which is correlated with higher mortality. Many studies have suggested antimicrobial de-escalation as one of the strategies to replace the empirical broad-spectrum antimicrobial treatment using a narrower antimicrobial therapy, especially among patients with sepsis. However, antimicrobial de-escalation therapeutic effects in sepsis remains unclear. We therefore performed the present study in an attempt to assess efficacy and safety of antimicrobial de-escalation therapy in patients with sepsis.Methods:We will carry out a systematic literature search to establish the potentially eligible trials from electronic databases, including EMBASE (1980 to October 16, 2020), MEDLINE via PubMed (1966 to October 16, 2020), Web of Science (1965 to October 16, 2020), Cochrane Library (CENTRAL; 2020, Issue 10), WanFang databases (last searched October 16, 2020), and China National Knowledge Infrastructure (CNKI; last searched October 16, 2020). For this study, the language restrictions are English or Chinese. Two authors independently examined quality based on the Cochrane Risk of Bias Tool V.2.0 and extracted data. Data obtained from the study will be synthesised using applicable statistical methods.Results:The results of the present study will systematically assess efficacy and safety of antimicrobial de-escalation therapy among patients with sepsis.Conclusion:The results of the present study will help to establish the efficacy and safety of antimicrobial de-escalation to treat patients with sepsis. It can also help to identify the most efficient and safe therapeutically-relevant method.Ethics and dissemination:The present study is a meta-analysis and the pooled results are based on published evidence. Therefore, ethics approval is not necessary.OSF registration number:October 22, 2020.osf.io/93wym. (https://osf.io/93wym/).

Current management of necrotizing soft-tissue infections.

The aim of the article is to present recent epidemiological, microbiological, and clinical data for the surgical, antimicrobial, and adjunctive management of necrotizing soft-tissue infections (NSTI). NSTI can be caused by a broad variety of organisms. Reports about NSTI caused by multidrug-resistant bacteria are increasing. Owing to the rareness of NSTI, general clinical awareness is low and prompt diagnosis is often delayed. New diagnostic instruments (scoring systems, MRI) have either a low accuracy or are time consuming and cannot guide clinicians reliable currently. The value of adjunctive measures (intravenous immunoglobulin, hyperbaric oxygen therapy) is uncertain as well. Morbidity and mortality in NSTI remain high, ranging from 20 up to over 30%. Early radical surgical debridement and empirical broad-spectrum antimicrobial treatment remain the cornerstones of therapy in NSTI. Further clinical research is necessary to shorten diagnostic pathways and to optimize surgical, antimicrobial, and adjunctive treatment.

EP13 A case of candida albicans septic sacroiliitis complicating severe COVID-19 infection

Case report - IntroductionBacterial and fungal infections are recognised complications of viral pneumonia, particularly in patients who are critically ill. We describe a case of fungal sacroiliitis complicating severe COVID-19 pneumonia following a prolonged intensive care unit (ICU) admission.Candida albicans sacroilitis is a rarely reported infection with few case reports in the literature. Candida osteoarticular infections can present as septic arthritis, with knee involvement in 75% of cases, or osteomyelitis. The latter presentation differs based on age - vertebral involvement (51%) is more common in adults while children are more likely to present with infection in the long bones, ribs, or sternum.Case report - Case descriptionA 48-year-old Afro-Caribbean gentleman with a history of hypertension and obesity was admitted to the ICU with clinical, laboratory and radiographic features of COVID-19 infection despite persistently negative swabs. Whilst in ICU he required mechanical ventilation. His stay was further complicated by multiple infections, pulmonary emboli, and the presence of a cavitating lesion in the left lung. Cultures from bronchoalveolar lavage and a central venous catheter line grew Serratia Mascense, candida glabrata and pseudomonas were isolated from his urine. He was treated with multiple antibiotics including meropenem, tazocin, ceftazidime and avibactam.After 61 days in the ICU he was transferred to the ward. He developed severe pain in his right hip which was worse on movement. This was followed by urinary incontinence and sensory deficit in the right L2/L3 dermatome. He underwent magnetic resonance imaging (MRI) of his spine and sacroiliac joints which showed right sided sacroiliitis and oedema around the iliopsoas muscle. He was started on vancomycin, later changed to ceftazidime avibactam and metronidazole. An echocardiogram did not show any vegetations. He underwent a biopsy of his sacroiliac joints which confirmed the presence of leucocytes, extended cultures yielded candida albicans in one out of two biopsy specimens.Considering ongoing pyrexia, pain and inflammatory markers, intravenous fluconazole was added to his antibiotic regimen which resulted in a marked improvement in mobility. After four weeks, ceftazidime, metronidazole and avibactam were stopped, and fluconazole was administered as oral tablets. 6 days later he became febrile and IV fluconazole was restarted.A repeat chest CT showed resolution of the cavity but ongoing changes suggestive of organising pneumonia. A repeat MRI of the sacroiliac joints revealed minor improvement. Intravenous Fluconazole was continued for a total of 8 weeks and was changed to tablets for complete a total of 12 weeks.Case report - DiscussionThis is a severe case of COVID-19 infection who despite 9 negative PCR tests, on day 53, had positive IgG for SARS-CoV-2 infection, confirming our clinical suspicion. Particularly in the ICU setting, individuals are approximately ten times more likely to have secondary bacterial/fungal infections with more frequent detection of multidrug-resistant Gram- negative pathogens.This case highlights several difficulties. Urine cultures had confirmed candida albicans, likely to be related to catheter related urinary tract infections, and a possible source for our patient but also a resistant pseudomonas aeruginosa species. Furthermore, cultures were positive for Serratia Mascense, candida glabrata. He had also already been treated with prolonged, broad spectrum antimicrobial treatment. Considering this, establishing the aetiology of the septic sacroiliitis was challenging. The rarity of candida sacroiliitis and presence of the organism in just one specimen made this more difficult. This led to the decision of a repeat sacroiliac biopsy to supply sufficient samples for further microbial analyses such as 16S, 18S and mycobacteria culture, all of which were negative.He became febrile after the discontinuation of antimicrobials and a switch to oral fluconazole therapy. He was extensively re-investigated and despite resolution of the lung cavity, there were changes which could have been consistent with an organising pneumonia. At this point he was neutropenic, mildly eosinophilic, and therefore a drug reaction was also considered.Repeat MRI revealed resolving muscle inflammation and minimal change at the bone site, with erosions and possible reactive bone marrow oedema. Following discussion with microbiology the decision was made to persist with intravenous Fluconazole. He continued to improve, and his inflammatory markers normalised after 8 weeks of treatment. Prednisolone was started for COVID-19 related pneumonitis. Long-term antifungal treatment is advisable, and we aim to complete 12 weeks of treatment. Case report - Key learning points  Patients with SARS-CoV-2 infection, particularly those requiring ICU admission were at risk of developing superinfections with multidrug-resistant Gram-negative bacteria or fungal infections.Candida albicans sacroiliitis is rare therefore early aspiration/biopsy is essential for the management.Longer treatment is needed in osteoarticular candida infections, even up to 6 or 12 months, therefor long-term close monitoring of this patients is essential.The utility and timing of reimaging patients following such infections is still unclearClose multidisciplinary and interdisciplinary team collaboration is essential in the management of this complex patients

Antimicrobial susceptibility of bacterial isolates from 33 thoroughbred horses with arytenoid chondropathy (2005-2019).

To describe the prevalence and antimicrobial susceptibility of bacterial isolates cultured from surgical specimens of infected arytenoid cartilage and granulomas. Retrospective cohort study. Thirty-three thoroughbred horses. Hospital records were retrieved for all horses admitted to a referral hospital for arytenoid chondropathy surgery that had samples submitted for culture and sensitivity between 2005 and 2019. Descriptive analyses were performed. In total, 56 bacterial isolates were obtained. Gram-positive bacteria (58%), Gram-negative bacteria (54%), and anaerobes (33%) were cultured from samples. Fifty-eight percent of horses had multiple bacteria isolated. Streptococcus spp were the most common (32%), followed by Enterobacteriaceae (13%). Bacterial isolates were sensitive to ceftiofur (83%), followed by ampicillin (64%), tetracycline (48%), enrofloxacin (45%), trimethoprim-sulfamethoxazole (41%), and gentamicin (18%). Multidrug resistance (MDR) was present in 44% of bacterial isolates. A wide variety of bacteria was cultured, providing evidence that secondary opportunistic infection by common respiratory bacteria is likely a factor in arytenoid chondropathy. Multidrug resistance was higher than what has been previously reported in equine respiratory samples. Trimethoprim-sulfamethoxazole had low effectiveness. Because culture and sensitivity testing is not available in the diagnosis of mild to moderate arytenoid chondropathy, the information from this study may allow for more targeted broad-spectrum antimicrobial treatment to limit disease progression when the disease is first identified. The antimicrobial susceptibilities and MDR found in this study emphasize the importance of following current antimicrobial guidelines and highlight the requirement for surgical intervention rather than continued medical treatment in cases that do not resolve with initial antimicrobial therapy.

12-year analysis of incidence, microbiological profiles and in vitro antimicrobial susceptibility of infectious keratitis: the Nottingham Infectious Keratitis Study

Background/aimsTo examine the incidence, causative microorganisms and in vitro antimicrobial susceptibility and resistance profiles of infectious keratitis (IK) in Nottingham, UK.MethodsA retrospective study of all patients who were diagnosed with...

Treatment of Invasive Fungal Infections in Haematology-Oncology Patients

Immunocompromised patients, those with cancer or haematological malignancies and allogeneic bone marrow/haematopoietic stem cell transplant recipients carry a high risk of invasive fungal infection (IFI), which is frequently life threatening. The most common causes of IFIs are Aspergillus and Candida species. Patients who receive long-term corticosteroids or broadspectrum antimicrobial treatment or total parenteral nutrition; patients […]

Cutaneous tuberculosis in HIV-infected individuals: Lessons learnt from a case series

Introduction:  Extrapulmonary tuberculosis (TB) causes a significant burden of disease worldwide, especially among HIV-infected individuals and those with other immunosuppressive conditions. Cutaneous TB is an important manifestation of extrapulmonary TB but is uncommonly reported in South Africa despite the high burden of HIV and TB co-infection. There is a paucity of published data on clinical presentation and outcome of cutaneous TB in this context. Raising awareness of this condition among clinicians is imperative to improve early diagnosis and optimise treatment outcomes. Patient presentation:  In this series, we present three cases of cutaneous TB, two adults and one child, referred to a tertiary hospital from two primary healthcare centres and from a general practitioner. We demonstrate that the clinical presentation is diverse, ranging from papular lesions to abscesses, and that concordant pulmonary TB may be present. Management:  In particular, we show the importance of performing diagnostic procedures (e.g. aspiration) in individuals presenting with an abscess that does not respond to broad spectrum antimicrobial treatment, particularly in those with advanced immunosuppression. Outcome and conclusion:  The outcome of our three patients was poor, highlighting the need for earlier diagnosis in this WHO Stage 4 condition and intensive management of clinical cases. Keywords:  HIV-medicine; Retro-Viral Disease; Mycobacteria; Tuberculosis; Multidrug Resistance; Cutaneous Tuberculosis; Cutaneous Disease; immunocompromised.

Factors associated with bacteraemia due to multidrug-resistant organisms among bacteraemic patients with multidrug-resistant organism carriage: a case control study

BackgroundInfections caused by multidrug-resistant organisms (MDRO) are emerging worldwide. Physicians are increasingly faced with the question of whether patients need empiric antibiotic treatment covering these pathogens. This question is especially essential among MDRO carriers. We aim to determine the occurrence of MDRO bacteraemia among bacteraemic patients colonized with MDRO, and the associated factors with MDRO bacteraemia among this population.MethodsWe performed a retrospective monocentric study among MDRO carriers hospitalized with bacteraemia between January 2013 and August 2016 in a French hospital. We compared characteristics of patients with MDRO and non-MDRO bacteraemia.ResultsOverall, 368 episodes of bacteraemia were reviewed; 98/368 (26.6%) occurred among MDRO carriers.Main colonizing bacteria were extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (40/98; 40.8%), ESBL-producing Klebsiella pneumoniae (35/98; 35.7%); methicillin-resistant Staphylococcus aureus (26/98; 26.5%) and multidrug-resistant Pseudomonas aeruginosa (PA) (12/98; 12.2%).There was no significant difference considering population with MDRO bacteraemia vs. non-MDRO bacteraemia, except for immunosuppression [OR 2.86; p = 0.0207], severity of the episode [OR 3.13; p = 0.0232], carriage of PA [OR 5.24; p = 0.0395], and hospital-acquired infection [OR 2.49; p = 0.034].In the multivariate analysis, factors significantly associated with MDRO bacteraemia among colonized patient were only immunosuppression [OR = 2.96; p = 0.0354] and the hospital-acquired origin of bacteraemia [OR = 2.62; p = 0.0427].ConclusionsAccording to our study, occurrence of bacteraemia due to MDRO among MDRO carriers was high. Factors associated with MDRO bacteraemia were severity of the episode and hospital-acquired origin of the bacteraemia. Thus, during bacteraemia among patients colonized with MDRO, if such characteristics are present, broad-spectrum antimicrobial treatment is recommended.

Evaluation of a risk-guided strategy for empirical carbapenem use in febrile neutropenia

Febrile neutropenia (FN) is associated with substantial morbidity and necessitates empirical broad-spectrum antimicrobial treatment. In this prospective cohort study, a risk-guided management strategy for FN using empirical piperacillin/tazobactam (TZP) or a carbapenem was evaluated. The analysis involved 723 FN episodes in hospitalised adult patients, including those with severe sepsis or prior infection/colonisation with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Propensity score matching analysis was used to adjust for baseline differences between treatment groups and produced 267 matched pairs. The primary outcome was all-cause mortality. Secondary outcomes were the incidences of drug-resistant Gram-negative (including ESBL-producing) and Gram-positive bacterial isolates and of invasive pulmonary aspergillosis (IPA) and their associated mortality. There was no difference in mortality between empirical carbapenem and TZP [18/267 (6.7%) vs. 14/267 (5.2%); P = 0.466]. Higher incidences of drug-resistant Gram-negative isolates [77/267 (28.8%) vs. 26/267 (9.7%); P < 0.001], including ESBL-producing bacteria [57/267 (21.3%) vs. 16/267 (6.0%); P < 0.001], were observed in carbapenem-treated episodes where its use lowered mortality. Mortality rates for ESBL-positive infections were 5.3% (3/57) and 25.0% (4/16) (P = 0.037) and for drug-resistant Gram-negative infections were 6.5% (5/77) and 23.1% (6/26) (P = 0.018) in carbapenem- and TZP-treated episodes, respectively. More IPA was observed with carbapenem use [16/267 (6.0%) vs. 6/267 (2.2%); P = 0.029]. Antifungal prophylaxis reduced the risk of death (odds ratio = 0.39, 95% confidence interval 0.17-0.87; P = 0.017). Risk-guided carbapenem prescribing in FN correctly identified cases prone to drug-resistant Gram-negative infections and reduced the mortality in these episodes.

Investigation of Clostridium difficile ribotypes in symptomatic patients of a German pediatric oncology center.

Under strict standard hygiene and contact isolation for symptomatic patients, genotyping of clinical isolates revealed that in pediatric cancer patients, CDI is not necessarily based on nosocomial transmission. The rate of CDI-related severe complications was low. What is Known: • Pediatric cancer patients face an increased risk of Clostridium difficile-associated disease due to immunosuppression, cancer chemotherapy, mucositis, and dysbiosis following intravenous broad-spectrum antimicrobial treatment. • C. difficile may be transmitted from patient to patient. What is New: • Under strict standard hygiene and contact isolation for symptomatic patients, genotyping of clinical isolates revealed that in pediatric cancer patients, CDI is not necessarily based on nosocomial transmission. • The rate of CDI-related severe complications was low.