BACKGROUND: Osteoarticular infections are fairly common in children but often these are associated with underdiagnosis, delayed diagnosis and improper management. This leads to an increased incidence of complications and poor outcomes. Given the paucity of standard protocols for the management of these children in the Indian context, Indian Academy of Pediatrics (IAP) has taken the initiative to formulate guidelines for the early diagnosis and rational management of bone and joint infections (BJIs).
OBJECTIVE: To critically evaluate the current evidence and formulate consensus guidelines for the diagnosis and management of BJIs in children.
METHODS: A committee comprising of eminent national faculty from different parts of the country who are experts in the field of Pediatric Infectious Diseases, Pediatric Orthopedics and Musculoskeletal Radiology was constituted and duly approved by the IAP. On Jan 16, 2021, a virtual meeting was held and a detailed discussions were carried out regarding the need to formulate these guidelines. Subsequently, the expert group defined the key questions in the first stage followed by collection and review of scientific evidences including available national and international recommendations or guidelines. This was followed by detailed deliberation among group members and presentation of their recommendations. The same were finalized in an online meeting on Aug 01, 2021, and a consensus statement was developed and adopted by the group.
UNASSIGNED: BJIs are medical emergencies that need early diagnosis and appropriate therapy to prevent long term sequelae like limb deformities. Bacterial infections like Staphylococcus aureus is the most common etiological agent. Nonspecific and subtle clinical manifestations make the diagnosis of pediatric BJIs more challenging. Diagnosis of BJIs is primarily clinical, supplemented by laboratory and radiological investigations. The choice of antibiotic(s), mode of administration and duration of therapy requires individualization depending upon the severity of infection, causative organism, regional sensitivity patterns, time elapsed between onset of symptoms and the child\'s presentation, age, risk factors and the clinical and laboratory response to treatment. There is paucity of appropriate guidelines regarding the diagnosis and management of BJIs in children in Indian context. Hence, the need for this expert consensus guidelines in Indian settings.

Cardiovascular implantable electronic device (CIED) implantation has markedly increased over the past 2 decades. Staphylococcus aureus bacteremia (SAB) occurs in patients with CIED, and determination of device infection often is difficult.
The purpose of this study was to examine the rate and clinical characteristics of SAB in patients living with CIED using the 2019 European Heart Rhythm Association (EHRA) international consensus document.
We conducted a retrospective study of patients with CIED who were hospitalized at Mayo Clinic, Rochester, with SAB from 2012 to 2019. Patients who met CIED infection criteria after SAB based on EHRA criteria were identified. A descriptive statistic and time-dependent Cox model were used.
Overall, 110 patients with CIED developed SAB, of whom 92 (83.6%) underwent transesophageal echocardiogram (TEE). Fifty-seven (51.8%) and 31 (28.2%) patients met criteria for definite and possible CIED infections, respectively. At 30-day follow-up, the cumulative rate of patients undergoing complete device extraction was 80.0% in the definite CIED infection group, compared with 38.8% and 32.9% in the possible and rejected CIED infection groups, respectively. We found that CIED extraction was associated with an 83% reduction in risk of 1-year mortality in the definite CIED infection group.
The rate of CIED infections after SAB was higher than that reported previously. Increased use of TEE and a novel case definition with broader diagnostic criteria likely were operative, in part, in accounting for the higher rate of CIED infections complicating SAB. Complete device removal is critical in patients with definite CIED infection to improve 1-year mortality.

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BACKGROUND: The consistently increasing reports of bacterial resistance and the reemergence of bacterial epidemics have inspired the health and scientific community to discover new molecules with antibacterial potential continuously. Frog-skin secretions constitute bioactive compounds essential for finding new biopharmaceuticals. The exact antibacterial characterization of dermaseptin related peptides derived from Agalychnis annae, is limited. The resemblance in their conserved and functionally linked genomes indicates an unprecedented opportunity to obtain novel bioactive compounds.
OBJECTIVE: In this study, we derived a novel peptide sequence and determined its antibacterial potentials.
METHODS: Consensus sequence strategy was used to design the novel and active antibacterial peptide named \'AGAAN\' from skin secretions of Agalychnis annae. The in-vitro activities of the novel peptide against some bacterial strains were investigated. Time kill studies, DNA retardation, cytotoxicity, betagalactosidase, and molecular computational studies were conducted.
RESULTS: AGAAN inhibited P. aeruginosa, E. faecalis, and S. typhimurium at 20 μM concentration. E. coli and S. aureus were inhibited at 25 μM, and lastly, B. subtilis at 50 μM. Kinetics of inactivation against exponential and stationary growing bacteria was found to be rapid within 1-5 hours of peptide exposure, depending on time and concentration. The peptide displayed weak hemolytic activity between 0.01%-7.31% at the antibacterial concentrations. AGAAN efficiently induced bacterial membrane damage with subsequent cell lysis. The peptide\'s DNA binding shows that it also targets intracellular DNA by retarding its movement. Our in-silico molecular docking analysis displayed a strong affinity to the bacterial cytoplasmic membrane.
CONCLUSIONS: AGAAN exhibits potential antibacterial properties that could be used to combat bacterial resistance.

Staphylococcus aureus sortase A (SaSrtA) is an enzyme that anchors proteins to the cell surface of Gram-positive bacteria. During the transpeptidation reaction performed by SaSrtA, proteins containing an N-terminal glycine can be covalently linked to another protein with a C-terminal LPXTG motif (X being any amino acid). Since the sortase reaction can be performed in vitro as well, it has found many applications in biotechnology. Although sortase-mediated ligation has many advantages, SaSrtA is limited by its low enzymatic activity and dependence on Ca2+. In our study, we evaluated the thermodynamic stability of the SaSrtA wild type and found the enzyme to be stable. We applied consensus analysis to further improve the enzyme\'s stability while at the same time enhancing the enzyme\'s activity. As a result, we found thermodynamically improved, more active and Ca2+-independent mutants. We envision that these new variants can be applied in conjugation reactions in low Ca2+ environments.

BACKGROUND: Necrotising otitis externa is a progressive infection of the external auditory canal which extends to affect the temporal bone and adjacent structures. Progression of the disease process can result in serious sequelae, including cranial nerve palsies and death. There is currently no formal published treatment guideline.
OBJECTIVE: This study aimed to integrate current evidence and data from our own retrospective case series in order to develop a guideline to optimise necrotising otitis externa patient management.
METHODS: A retrospective review of necrotising otitis externa cases within NHS Lothian, Scotland, between 2013 and 2018, was performed, along with a PubMed review.
RESULTS: Prevalent presenting signs, symptoms and patient demographic data were established. Furthermore, features of cases associated with adverse outcomes were defined. A key feature of the guideline is defining at-risk patients with initial intensive treatment. Investigations and outcomes are assessed and treatment adjusted appropriately.
CONCLUSIONS: This multi-departmental approach has facilitated the development of a succinct, systematic guideline for the management of necrotising otitis externa. Initial patient outcomes appear promising.

We reported the impact of internal guidelines coupled with selective reporting of antibiotic susceptibility tests (srAST) on antibiotic adequacy in healthcare facilities.
This prospective study involved clinicians from three clinics with medical and surgical activities employing a full-time infectious disease (ID) specialist. Internal guidelines were updated in 2016. The clinics were working with the same laboratory, which delivered the srAST introduced in March 2017. Two weeks per month over a 6-month period, all isolated bacterial specimens, empirical antibiotic therapies (EAT) and the documented ones were analyzed. An EAT listed in the guidelines and a documented therapy mentioned in the srAST defined their adequacy.
A total of 257 positive bacterial samples were analyzed in 199 patients, for which 106 infections were studied. Of these, 32% were urinary tract infections, 15% were primary bloodstream infections, 11% were bone infections, and 42% were other types of infection. The three main bacteria were Escherichia coli (27%), Staphylococcus aureus (24%), and Enterococcus faecalis (14%). The total number of antibiotic prescriptions was 168, with 75 (45%) EATs and 93 (55%) documented therapies. There were 35/75 (47%) adequate EATs and 86/93 (92%) adequate documented therapies. The ID specialist was not involved in 90/168 (53.5%) prescriptions, of which 43/90 (48%) were adequate, with 21/35 (60%) EATs and 22/86 (25%) documented therapies. There was a statistical correlation between compliance of the EATs with guidelines and of the documented therapy with srAST (p=0.02).
Combining internal guidelines and srAST led to a high rate of antibiotic adequacy.

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The aim of this survey was to identify a set of actions aimed to improve the diagnosis and management of acute bacterial skin and skin-structure infections (ABSSSIs) and the implementation of some principles of antimicrobial stewardship (AMS) in this setting.
A list of 76 statements for which there was a lack of clarity were generated by an expert panel and were validated by a group of experts. The questionnaire was administered to 112 experts in infectious diseases or microbiology. Participants were asked to vote on a list of statements. An agreement threshold of 66% was required to reach consensus.
Overall, 57 responders participated in the survey. Positive consensus was reached on the fact that ABSSSIs represent a significant cause of infection in the emergency department, are frequently associated with increased hospital stay and are mainly caused by Staphylococcus aureus. The panellists strongly supported collection of samples from purulent infections by needle aspiration as well as collection of blood cultures in the presence of signs/symptoms of systemic infection. The importance of source control and prompt adequate microbiological documentation, the objective to reduce the length of hospital stay, the choice of a narrow-spectrum antibiotic and the role of new therapeutic options (e.g. long-acting drugs) in improving compliance also reached a positive consensus.
This Delphi survey provides useful indicators for the implementation of AMS principles in the clinical management of ABSSSI and offers interesting elements of discussion about the barriers existing in Europe for optimal implementation of AMS programmes.