Synthetic polyploidization induces enhanced phytochemical profile and biological activities in Thymus vulgaris L. essential oil.

Essential oil from Thymus vulgaris L. has valuable therapeutic potential that is highly desired in pharmaceutical, food, and cosmetic industries. Considering these advantages and the rising market demand, induced polyploids were obtained using oryzalin to enhance essential oil yield. However, their therapeutic values were unexplored. So, this study aims to assess the phytochemical content, and antimicrobial, antioxidant, and anti-inflammatory activities of tetraploid and diploid thyme essential oils. Induced tetraploids had 41.11% higher essential oil yield with enhanced thymol and γ-terpinene content than diploid. Tetraploids exhibited higher antibacterial activity against all tested microorganisms. Similarly, in DPPH radical scavenging assay tetraploid essential oil was more potent with half-maximal inhibitory doses (IC50) of 180.03 µg/mL (40.05 µg TE/mg) than diploid with IC50 > 512 µg/mL (12.68 µg TE/mg). Tetraploids exhibited more effective inhibition of in vitro catalytic activity of pro-inflammatory enzyme cyclooxygenase-2 (COX-2) than diploids at 50 µg/mL concentration. Furthermore, molecular docking revealed higher binding affinity of thymol and γ-terpinene towards tested protein receptors, which explained enhanced bioactivity of tetraploid essential oil. In conclusion, these results suggest that synthetic polyploidization using oryzalin could effectively enhance the quality and quantity of secondary metabolites and can develop more efficient essential oil-based commercial products using this induced genotype.

Estimating Vitamin D threshold for the Indian population: Delving into the actual disease burden.

Background: Based on the current guidelines in practice, a vast majority of the healthy Indian population is vitamin D deficient. Since the serum 25 hydroxycholecalciferol (25HCC) levels are affected by race and skin pigmentation, the normal range of vitamin D may differ in the Indians compared to the Western population. This study attempted to determine a population-specific threshold for 25 HCC levels associated with adequate bone health and calcium and phosphate homeostasis in healthy Indians. Methods: Subjects aged 20-50 years were included in the study. The exclusion criteria were obesity, chronic renal disease, liver failure, diabetes mellitus, thyroid disorders, a recent history of fracture, constant joint pain, and postmenopausal status. In addition, participants on prescribed medication such as glucocorticoids, anticonvulsants, or antifungals, as well as vitamin D and calcium supplementation, were also excluded.Blood samples were analyzed for serum calcium, phosphate, alkaline phosphatase, 25HCC, 1,25dihydroxycholecalciferol, parathyroid hormone (PTH), procollagen type-I N propeptide, and C-terminal telopeptide of type 1 collagen.Locally estimated smoothing scatter plot (LOESS) curves and Spearman correlation were utilized to study the correlation of all the biochemical parameters with 25 HCC to achieve thresholds. Results: The study consisted of 270 healthy participants, out of which 97.8% were found to have vitamin D levels below 30 ng/ml. In addition, 8.8% had raised PTH, and 1.85% had hypocalcemia. Furthermore, 1.48% had raised serum alkaline phosphatase and hypophosphatemia, respectively. A weak inverse correlation was seen between 25 HCC and PTH (rs = -0.437, p < 0.001), as well as alkaline phosphatase (rs = -0.1475, p = 0.015), while a weak positive correlation was seen with serum phosphate (rs = 0.128, p = 0.047). Conclusion: For a healthy Indian population, the reference range of 25 HCC is much lower, and the lower limit of normal is approximately 13.5 ng/ml. This study indicates that vitamin D insufficiency in this population starts at 25 HCC values of 13.5 ng/ml and deficiency at 7 ng/ml.

Essential role of Mg2+ in mouse preimplantation embryo development revealed by TRPM7 chanzyme-deficient gametes.

TRPM7 (transient receptor potential cation channel subfamily M member 7) is a chanzyme with channel and kinase domains essential for embryo development. Using gamete-specific Trpm7-null lines, we report that TRPM7-mediated Mg2+ influx is indispensable for reaching the blastocyst stage. TRPM7 is expressed dynamically from gametes to blastocysts; displays stage-specific localization on the plasma membrane, cytoplasm, and nucleus; and undergoes cleavage that produces C-terminal kinase fragments. TRPM7 underpins Mg2+ homeostasis, and excess Mg2+ but not Zn2+ or Ca2+ overcomes the arrest of Trpm7-null embryos; expressing Trpm7 mRNA restores development, but mutant versions fail or are partially rescued. Transcriptomic analyses of Trpm7-null embryos reveal an abundance of oxidative stress-pathway genes, confirmed by mitochondrial dysfunction, and a reduction in transcription factor networks essential for proliferation; Mg2+ supplementation corrects these defects. Hence, TRPM7 underpins Mg2+ homeostasis in preimplantation embryos, prevents oxidative stress, and promotes gene expression patterns necessary for developmental progression and cell-lineage specification.

Chickpea Peptide: A Nutraceutical Molecule Corroborating Neurodegenerative and ACE-I Inhibition.

Chickpea seeds are the source of proteins in human nutrition and attribute some nutraceutical properties. Herein, we report the effects of chickpea seed bioactive peptide on albumin, insulin, lactoglobulin and lysozyme amyloid fibril formation. Employing thioflavin T (ThT) assays and circular dichroism (CD), amyloid structural binding transition was experimented to analyze the inhibition of amyloid fibril formation. The purified active peptide with a molecular mass of 934.53 Da was evaluated in vitro for its ACE-I inhibitory, antibacterial, antifungal and antidiabetic activities. Further, in vivo animal studies were carried out in wistar rats for blood pressure lowering action. In hypertensive rats, chickpea peptide decreased 131 ± 3.57 mm of Hg for systolic blood pressure and 86 ± 1.5 mm of Hg for diastolic blood pressure after 8 h intraperitoneal administration. Additionally, the peptide suppressed the fibrillation of amyloid and destabilized the preformed mature fibrils. Data emphasize efficacy of chickpea peptide vis-a-vis ACE-Inhibitory, antibacterial, antifungal, antidiabetic and anti-amyloidogenic activities, allowing us to propose this novel peptide as a suitable candidate for nutraceutical-based drugs and seems the first kind of its nature.

In Silico Prediction, Molecular Docking and Dynamics Studies of Steroidal Alkaloids of Holarrhena pubescens Wall. ex G. Don to Guanylyl Cyclase C: Implications in Designing of Novel Antidiarrheal Therapeutic Strategies.

The binding of heat stable enterotoxin (STa) secreted by enterotoxigenic Escherichia coli (ETEC) to the extracellular domain of guanylyl cyclase c (ECDGC-C) causes activation of a signaling cascade, which ultimately results in watery diarrhea. We carried out this study with the objective of finding ligands that would interfere with the binding of STa on ECDGC-C. With this view in mind, we tested the biological activity of a alkaloid rich fraction of Holarrhena pubescens against ETEC under in vitro conditions. Since this fraction showed significant antibacterial activity against ETEC, we decided to test the screen binding affinity of nine compounds of steroidal alkaloid type from Holarrhena pubescens against extracellular domain (ECD) by molecular docking and identified three compounds with significant binding energy. Molecular dynamics simulations were performed for all the three lead compounds to establish the stability of their interaction with the target protein. Pharmacokinetics and toxicity profiling of these leads demonstrated that they possessed good drug-like properties. Furthermore, the ability of these leads to inhibit the binding of STa to ECD was evaluated. This was first done by identifying amino acid residues of ECDGC-C binding to STa by protein-protein docking. The results were matched with our molecular docking results. We report here that holadysenterine, one of the lead compounds that showed a strong affinity for the amino acid residues on ECDGC-C, also binds to STa. This suggests that holadysenterine has the potential to inhibit binding of STa on ECD and can be considered for future study, involving its validation through in vitro assays and animal model studies.

Facile functionalization of Teriflunomide-loaded nanoliposomes with Chondroitin sulphate for the treatment of Rheumatoid arthritis.

This research aims to coat Teriflunomide (TEF) loaded conventional nanoliposomes (CON-TEF-LIPO) with Chondroitin sulphate (CS) to produce CS-TEF-LIPO for the effective treatment of Rheumatoid arthritis (RA). Both CON-TEF-LIPO and CS-TEF-LIPO were produced, characterized and evaluated for their active targeting potential towards CD44 receptors. Cell cytotoxicity, cell viability and intracellular uptake study on differentiated U937 and MG-63 cells demonstrated the active targeting of CS-TEF-LIPO towards CD44 receptors. Furthermore, in vivo pharmacodynamic, biochemical, radiological and histopathological studies performed in adjuvant induced arthritic (AIA) rat model showed a significant (P < 0.05) reduction in inflammation in arthritic rat paw in CS-TEF-LIPO group compared to TEF and CON-TEF-LIPO groups. Moreover, liver toxicity study revealed that CS-TEF-LIPO showed no signs of toxicity and biodistribution study revealed the accumulation of CS-TEF-LIPO in synovial region of arthritic rat. Taken together, results suggest that CS-TEF-LIPO could provide a new insight for an effective treatment of RA.

Case Report: Paragonimiasis Presenting with Pericardial Tamponade.

We report an unusual case of paragonimiasis in a Nepali patient presenting with massive pericardial effusion and pericardial tamponade. The patient reported neither the consumption of crabs or crayfish nor the consumption of wild animal meat, which are the usual sources of infection. It is suspected that the source of infection was instead the ingestion of raw live slugs as part of a traditional medicine treatment.

Collaborative Care for Depression of Adults and Adolescents: Measuring the Effectiveness of Screening and Treatment Uptake.

OBJECTIVE: This study analyzed effectiveness of screening, referrals, and treatment uptake of a collaborative care for depression intervention across 10 primary care clinics in Chicago. METHODS: Between November 2016 and December 2017, patients (N=25,369) were screened with the Patient Health Questionnaire-2 and the Patient Health Questionnaire-9 on the basis of an eligibility algorithm. Electronic health record data were analyzed for sample characteristics, screening rates, referrals, and treatment pathways. To identify disparities, a test of proportions was conducted between eligible and screened patients as well as referred and treated patients. RESULTS: Screenings, referrals, and uptake occurred proportionately across subgroups except for patients ages 12-17. Adolescent age was associated with disproportionate Patient Health Questionnaire-9 screenings and with treatment disengagement. CONCLUSIONS: The intervention shows promise in expanding access to care and reducing disparities. Greater access to psychotherapies and innovative treatment modalities, particularly for adolescents, may improve overall treatment uptake.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity.

BACKGROUND: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. METHODS: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. RESULTS: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 µg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. ß-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. CONCLUSION: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

ω-3 Fatty Acid Synergized Novel Nanoemulsifying System for Rosuvastatin Delivery: In Vitro and In Vivo Evaluation.

The present study was undertaken to improve rosuvastatin (RSV) bioavailability and pharmacological response through formation of SNES using Perilla frutescens oil as lipid carrier. The composition of oil was estimated by fatty acid methyl ester (FAME) analysis using gas chromatography. Solubility of RSV in Perilla frutescens oil and Cremophor EL was 25.0 ± 3.0 and 60.0 ± 5.0 mg/mL, respectively. Later, nanophasic maps and a central composite design were employed to determine the maximum nanoemulsion region and further optimize SNES in this study. Finally, the optimized formulation was evaluated in vitro and in vivo. FAME analysis revealed that PUFA content was 70.3% of total fatty acid. Optimized SNES formulation demonstrated particle size of 17.90 nm, dissolution 98.80%, cloud point 45°C, emulsification time 2 min, and viscosity 241.41 ± 5.52 cP. The hypolipidemic property of SNES was further explored using Triton X-100-induced hyperlipidemic rat model, and there were reductions of serum cholesterol, triglyceride, and LDL and VLDL levels in the SNES-treated group as compared to the toxic control. Pharmacokinetic study of SNES revealed significantly higher C max (60.13 ± 25.43 ng/mL) and AUC0-∞ (6195 ± 42.38 ng h/mL) vis-à-vis marketed tablet (284.80 ± 13.44 ng/mL, 3131.72 ± 51.93 ng h/mL, respectively). RSV was successfully incorporated into ω-3 fatty acid-based SNES with improved pharmacokinetic parameters (~ 2-fold improved bioavailability) and better hypolipidemic properties, owing to the synergistic effects of hepatic lipid regulation itself. The results clearly explicated that ω-3 fatty acid-based SNES effectively enhanced bioavailability and pharmacological responses of RSV, suggesting that these formulations may be useful as alternative for hyperlipidemia treatment in future drug design perspective.

Antibiotic Lock Therapy in the Era of Gram-Negative Resistance.

BACKGROUND: Central-line-associated blood-stream infection (CLABSI) is a highly consequential nosocomial infection. The most effective management includes the removal of the infected catheter. Retention of the catheter and antibiotic lock therapy (ALT) along with systemic antibiotics may be attempted only if there are unusual extenuating circumstances. CLABSIs due to Gram-negative bacteria (GNB) is more common in our setting and the organisms are often highly resistant. Hence, there is a need to explore the use of novel antimicrobials for catheter lock solutions along with antibiofilm agents. PATIENTS AND METHODS: We report the use of antibiotic lock therapy in the first 29 patients who had 37 episodes of bacteremia (CLABSI/symptomatic colonization) due to long-term catheters in our unit from February 2008 to September 2014. Patients received ALT if they had CLABSI or were symptomatic with a colonized catheter. Patients who needed removal of the catheter were ineligible for ALT. Patients received systemic antibiotic therapy and lock solutions were kept in the catheter for dwell times of 24 hours, and therapy was continued for 14 days. Successful treatment was defined as any of the following: 1) Clinical cure with disappearance of signs of sepsis 2) Microbiological cure with resolution of bacteremia (confirmed by a negative blood culture which was obtained through the catheter 2-5 days after stopping therapy. RESULTS: Among the 37 episodes treated with ALT, 30 episodes were caused by GNB and four episodes were caused by Gram-positive cocci (GPC); Enterococcus, methicillin-sensitive S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and methicillin-sensitive coagulase-negative staphylococcus (CoNS). There were three episodes of CRBSI due to Candida and one episode each due to L. monocytogens and Bacillus spp. Of the other 30 episodes due to GNB, Acinetobacter baumannii were isolated in eight episodes, Stenotrophomonas (n=6), E. coli (n=5), Flavobacterium (n=2), and P. aeruginosa (n=4), and B. cepacia in three episodes. The other organisms isolated were K. pneumoniae, and non-typhoidal Salmonella (1 episode each). Successful treatment with ALT was observed in 30 (81.08%) of the 37 episodes. CONCLUSIONS: In patients with CLABSI due to Gram-negative pathogens, the use of ALT along with systemic antibiotics has an excellent catheter salvage rate. Newer antibiotics (tigecycline and colistin) may be useful options as antibiotic lock solutions along with antibiofilm agents especially in the setting of resistant Gram-negative bacilli producing CLABSI.

Tendoachillis avulsion in osteomalacia.

Sixteen-year-old girl presented with generalized body pain with avulsion of tendoachillis on minimal trauma. Surgical repair led to complete recovery. Investigations revealed severe osteomalacia, which improved on supplementation. Surgical difficulty encountered was soft nature of bone, difficult attachment of tendon and delayed rehabilitation. Vitamin D evaluation is essential in young females presenting with generalized body pain and pain at attachments of strong muscles with bones.

Efficient shoots regeneration and genetic transformation of Bacopa monniera.

Bacopa monniera is an important source of metabolites with pharmaceutical value. It has been regarded as a valuable medicinal plant and its entire commercial requirement is met from wild natural population. Recently, metabolic engineering has emerged as an important solution for sustained supply of assured and quality raw material for the production of active principles. Present report describes efficient in vitro multiplication and transformation method for genetic manipulation of this species. MS medium supplemented with 2 mgl(-1) BA and 0.2 mgl(-1) IAA was found optimum for maximum shoot regeneration (98.33 %) from in vitro leaves with 2-3 longitudinal cuts. Agrobacterium tumefaciens-mediated transformation method was used for generating transgenic B. monniera plants. Putative transformants were confirmed by GUS assay and PCR based confirmation of hptII gene. DNA blot analysis showed single copy insertion of transgene cassette. An average of 87.5 % of the regenerated shoots were found PCR positive for hptII gene and GUS activity was detected in leaves of transgenic shoots at a frequency of 82.5 % The efficient multiple shoots regeneration system described herein may help in mass production of B. monniera plant. Also, the high frequency transformation protocol described here can be used for genetic engineering of B. monniera for enhancement of its pharmaceutically important metabolites.

A polymer-protein core-shell nanomedicine for inhibiting cancer migration followed by photo-triggered killing.

Migratory capacity of cancer plays a critical role in the process of metastasis. Aberrant focal adhesions activated by the phosphorylation of Src kinase enables cancer cells to anchor on its micro-environment and migrate towards biochemically favorable niche, causing metastasis. Effective blocking of the migratory capacity of cancer cells by inhibiting protein kinases and subsequent application of cytotoxic stress may provide better therapeutic outcome. Here, we report a novel core-shell nanomedicine that inhibits cancer migration by nano-shell and impart reactive oxygen stress by laser assisted photosensitization of nano-core. For this, we have optimized a polymer-protein nanoconstruct where a photosensitizer (5,10,15, 20-tetrakis(meso-hydroxyphenyl)porphyrin (mTHPP) is loaded into poly(lactic-co-glycolic acid) (PLGA) nano-core and Src kinase inhibitor (dasatinib) is loaded into albumin nano-shell. The polymer-core was prepared by electrospray technique and albumin-shell was formed by alcohol coacervation. Transmission electron microscopy studies revealed the formation of - 80 nm sized nano-core decorated with - 10 nm size nano-shell. Successful incorporation of monomeric mTHPP in nano-core resulted improved photo-physical properties and singlet oxygen release under physiological conditions compared to free-mTHPP. Core-shell nanomedicine also showed dose and time dependent cellular uptake in U87MG glioma cells. Dasatinib released from nano-shell caused down regulation of phospho-Src leading to significant impairment of cancer migration and subsequent laser assisted photosensitization of nano-core resulted in the release of reactive oxygen stress leading to apoptosis of spatially confined cancer cells. In vivo studies on Wistar rats indicated the absence of any significant toxicity caused by the intravenous administration of nanomedicine. These results clearly show the advantage of core-shell nanomedicine mediated combinatorial approach for inhibiting important cancer signalling pathways togother with imparting cytotoxic stress.

A systematic review of yoga for state anxiety: considerations for occupational therapy.

BACKGROUND: State anxiety can result from a variety of life situations. This type of anxiety can disrupt occupational engagement and performance, thereby affecting rehabilitation and recovery. Occupational therapists need to address the connection between mind-body-spirit and its relationship to performance and engagement in meaningful occupations. Yoga, when used as an adjunct to therapy, has the potential to address state anxiety. PURPOSE: The aim was to systematically review the evidence concerning the effectiveness of yoga as a treatment approach for state anxiety. METHODS: Six electronic databases, the authors' own files, and the references of included studies from 1990 to July 2011 were searched. FINDINGS: A total of 25 unique studies represented by 26 publications made up the sample: two systematic reviews; 16 randomized controlled trials, and seven prospective, controlled, non-randomized studies. Evidence suggests yoga can be a viable therapeutic option for reducing state anxiety in certain situations. IMPLICATIONS: In making the determination to recommend yoga as an intervention, occupational therapists should consider the client's circumstances and values as well as the type and intensity of the yoga program.

Simultaneous inhibition of aberrant cancer kinome using rationally designed polymer-protein core-shell nanomedicine.

Simultaneous inhibition of deregulated cancer kinome using rationally designed nanomedicine is an advanced therapeutic approach. Herein, we have developed a polymer-protein core-shell nanomedicine to inhibit critically aberrant pro-survival kinases (mTOR, MAPK and STAT5) in primitive (CD34(+)/CD38(-)) Acute Myeloid Leukemia (AML) cells. The nanomedicine consists of poly-lactide-co-glycolide core (~250 nm) loaded with mTOR inhibitor, everolimus, and albumin shell (~25 nm thick) loaded with MAPK/STAT5 inhibitor, sorafenib and the whole construct was surface conjugated with monoclonal antibody against CD33 receptor overexpressed in AML. Electron microscopy confirmed formation of core-shell nanostructure (~290 nm) and flow cytometry and confocal studies showed enhanced cellular uptake of targeted nanomedicine. Simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells, was demonstrated using immunoblotting, cytotoxicity and apoptosis assays. This cell receptor plus multi-kinase targeted core-shell nanomedicine was found better specific and tolerable compared to current clinical regime of cytarabine and daunorubicin. FROM THE CLINICAL EDITOR: These authors demonstrate simultaneous inhibition of critical kinases causing synergistic lethality against leukemic cells, without affecting healthy blood cells by using rationally designed polymer-protein core-shell nanomedicine, provoding an advanced method to eliminate cancer cells, with the hope of future therapeutic use.

The relevance of ESBL producing isolates in patients surgically treated for acute appendicitis.

BACKGROUND: In India, there is a high prevalence of ESBL producing organisms among intraabdominal isolates and in stool flora of 'normal' individuals. Hence, it may be presumed that unless antimicrobial therapy effective for ESBL flora is used perioperatively for abdominal surgery, the outcome will be adverse. We selected patients surgically treated for appendicitis as a model to explore the relevance of ESBL producing isolates in this retrospective observational study. AIMS AND OBJECTIVES: To assess the impact of ESBL producing isolates in patients surgically treated for acute appendicitis and to determine whether the perioperative antibiotic use needs to be changed in view of the high ESBL prevalence. METHOD: Chart review of 221 consecutive patients who had undergone appendicectomy between January 2004 and December 2009. RESULTS: 55 of 221 patients had cultures of relevant specimens done based on the discretion of the treating surgeon. 40 yielded 1 or more organisms. 19 showed ESBL producing Enterobacteriaceae (ESBL+) and 21 showed non ESBL producing Enterobacteriaceae (ESBL-). 118 of 221 patients had presented without any complications and had a good outcome after surgery. The other 33 of 221 patients had complications like perforation or an abscess at presentation. Out of these, 16 patients received inappropriate therapy and 17 received appropriate therapy. The patients with appropriate therapy had good outcome. Among the 16 patients with inappropriate therapy 15 were ESBL+and 1 was ESBL-. Out of the 15 ESBL+isolates, 9 developed an initial postoperative complication like postoperative fever or wound infection. The cultures of the relevant specimen were done in all these 9 patients, all of which were positive. Therapy was changed in 7 of these 9 patients to pathogen directed therapy like amikacin, chloramphenicol and levofloxacin. Meropenem was used in only one case. All these 7 patients as well as the 2 patients whose treatment was not changed made a complete recovery. CONCLUSION: For patients surgically treated for acute appendicitis, a change of perioperative antibiotics to those effective for ESBL+organisms is not needed at present only on the basis of ESBL prevalence rates. Routine cultures may not be necessary. Cultures are needed if there is a complication such as an abscess or perforation at presentation or an initial post operative complication. A change to pathogen directed therapy, including even to older or non beta-lactam antimicrobials may be needed in these cases. Our results support continuing the use of older antimicrobials rather than changing to carbapenems and beta-lactamase-beta-lactamase inhibitor combination in low risk surgically treated patients. This may prevent generation of further resistance without compromising outcomes.