Ceftolozane/Tazobactam In-Vitro Activity against Clinical Isolates from Complicated Intra-Abdominal Infection Patients in Three Indonesian Referral Hospitals.

Complicated intra-abdominal infections (cIAIs) lead to high morbidity and mortality, especially if poorly managed. However, Indonesia's microbial pattern and susceptibility data are limited, especially for new antibiotics. Ceftolozane/tazobactam (C/T) is reported to be a new potent antibiotic against various pathogens. Thus, we aim to investigate C/T in vitro activity against clinical isolates from cIAI patients. This prospective cross-sectional study was conducted in three major referral hospitals in Indonesia, including Dr. Cipto Mangunkusumo Hospital (Jakarta), Dr. Kariadi Hospital (Semarang), and Dr. Soetomo Hospital (Surabaya), enrolling those diagnosed with cIAIs. Blood specimens were collected before or after at least 72 h of the last antibiotic administration. Meanwhile, tissue biopsy/aspirate specimens were collected intraoperatively. These specimens were cultured, followed by a susceptibility test for specific pathogens. The minimum inhibitory concentration (MIC) of isolates was determined according to CLSI M100. Two-hundred-and-eighty-four patients were enrolled from 2019-2021. Blood culture was dominated by Gram-positive bacteria (GPB, n = 25, 52.1%), whereas abdominal tissue culture was dominated by Gram-negative bacteria (GNB, n = 268, 79.5%). The three most common organisms were GNB, including E. coli, K. pneumoniae, and P. aeruginosa. C/T was susceptible in 96.7%, 70.2%, and 94.1% of the E. coli, K. pneumoniae, and P. aeruginosa isolates, respectively. In addition, C/T also remained active against ESBL Enterobacterales and carbapenem-non-susceptible P. aeruginosa. Overall, C/T demonstrates a high potency against GNB isolates and can be considered an agent for carbapenem-sparing strategy for cIAI patients as the susceptibility is proven.

Oral Spermine Supplementation in Gestated Rabbit: A Study on Villi Height of Immature Intestines.

Introduction: Immature intestines are the major problem in prematurity. Postnatal oral spermine has been shown in studies to improve intestinal maturation in rats and piglets. This study aimed to find out the efficacy of spermine in rabbits during gestation. Method: An experimental study was done in an unblinded, randomized manner on those treated with and without spermine administration. A morphological examination of hematoxylin-eosin-stained villi was performed under a light microscope with a focus on villi height. Data were subjected to analysis. Results: The median of the spermine-treated group was found to be higher at 24, 26, and 28 days than the non-spermine group, but was not significantly different. Conclusion: Oral spermine supplementation during gestation might improve intestinal villi height in immature rabbit intestines.

Hyperbaric Oxygen Therapy for Second-Degree Burn Healing: An Experimental Study in Rabbits.

BACKGROUND: The wound healing process includes inflammation, proliferation, and remodelling phases, the main features of which are inflammation, neoangiogenesis, and epithelialization. Hyperbaric oxygen therapy (HBOT) is one modality postulated to improve wound healing. The objective of this study was to determine whether HBOT could improve selected features of burn wound healing in an experimental rabbit model. METHODS: Researchers conducted an experimental study with 36 rabbits given second-degree burns. Subjects were separated into two groups: a control group (n = 18) and an intervention group that was given HBOT at 2.4 atmospheres absolute for 6 days (n = 18). The main outcome measure was wound healing. RESULTS: Compared with the control group, the HBOT group showed more robust inflammatory cells (P = .025) and epithelialization (P = .024), but no significant difference in angiogenesis (P = .442). CONCLUSIONS: The authors conclude that HBOT may improve second-degree burn healing by increasing inflammatory cell migration and re-epithelialization.

Intact Glycocalyx of Intestinal Mucosa in Intraabdominal Infection: an Investigation Using Blood Group Antigen.

BACKGROUND: intestinal glycocalyx plays a role in bacterial translocation as the pathogenesis sepsis derived from intra-abdominal infections that vulnerable in certain blood types. However, the link between intestinal glycocalyx in specific types of blood groups and abdominal infections remains unknown. This study aims to find out the condition of intestinal glycocalyx in certain blood types with intraabdominal sepsis. METHODS: descriptive study involved subjects with intraabdominal infections who underwent laparotomy. Samples are in the form of intestinal specimens. The measurement of intestinal glycocalyx proceeded by the ELISA method using blood group antigens (A and B). Expression data on the secretors were analyzed using the Kolmogorov - Smirnov test followed by parametric comparisons using ANOVA and t-tests. RESULTS: there were 32 subjects with intra-abdominal infections studied in this study. All of them are secretors and express A and B antigens strongly. We found no difference between intraabdominal infections in those with complications or without complications. Blood type O is a predominant blood type found (43.8%). Escherichia coli is the most commonly found microbe in the culture (61.3%). CONCLUSION: this study shows there is no disrupted intestinal glycocalyx of sepsis patients caused by intraabdominal infection.

Clinical Practice Guidelines in Complicated Intra-Abdominal Infection 2018: An Indonesian Perspective.

BACKGROUND: The occurrence of complicated intra-abdominal infections (cIAI) remains high despite system improvement in accordance with Joint Commission International because of heterogeneity of management. However, published clinical practice guidelines (CPGs) were not feasible to be implemented because these guidelines were not specific to Indonesian characteristics. Thus, a national CPG should be developed to minimize heterogeneity in the management of cIAI in Indonesia. METHODS: We developed a CPG on cIAI through the adaptation of published CPGs. The process proceeded in steps recommended by ADAPTE. Published CPGs were critically appraised using Appraisal of Guidelines for Research and Evaluation (AGREE) II critical appraisal tools. For a specific updated CPG, the analysis was performed using Checklist for the Reporting of Updated Guidelines (CheckUp). Appropriate statements and recommendations in selected CPGs were adapted into our CPG with consideration of Indonesian characteristics. The recommendations were established by the hierarchy of evidence on Grading of Recommendations Assessment, Development and Evaluation (GRADE). The approval of the recommendation draft was performed using the Delphi method. RESULTS: Sixty-eight full-text guidelines were downloaded from several sites. Thirty-three CPGs were related to intra-abdominal infection and 18 others were specific on CPG on intra-abdominal infection and cIAI. On review of these 18 CPGs, 13 were strongly recommended, three were recommended, and two were not recommended. On review updated CPGs, five updated CPGs were found, all with the same score. Two of the strongly recommended updated CPGs had been published in 2016 and 2017, i.e. recommendations by the World Society of Emergency Surgery 2016 consensus conference and revised CPG of the Surgical Site Infection Society. There were a total of 84 statements and recommendations developed and approved by the task force through using the Delphi method. CONCLUSIONS: This guideline summarizes the definition, classification, pathophysiology, etiology, risk factors, assessments, and management of cIAI. Evidence-based recommendations have been developed with consideration of Indonesian-specific characteristics.

Methylene Blue Effectiveness as Local Analgesic after Anorectal Surgery: A Literature Review.

BACKGROUND: Methylene blue (MB) has been found to have unique analgesic property through temporary disruption of sensory nerve conduction. In anorectal surgery, MB is widely used as a biologic stain but the analgesic effect has never been studied. Thus, a literature review completed with critical appraisal is required to find out its efficacy. METHODS: A review has been run to find out its efficacy. Literature search proceeded in database sites, namely, PubMed, EBSCO, Cochrane, Wiley, and ProQuest using the following keywords: "anorectal" OR "hemorrhoid" OR "anal fistula" OR "anal fissure" OR "anal abscess" OR "anal pruritus" AND "methylene blue" AND "analgesic"; then the critical appraisal and its implication were discussed. RESULT: There were 491 articles in full text found, and four studies met the inclusion criteria. Two studies were focused on the evaluation of VAS in hemorrhoid surgery whereas the rest were focused on the evaluation of symptom score in anal pruritus. CONCLUSIONS: A study with level of evidence 2 on VAS showed the efficacy. The rest showed insufficient evidence due to variations of anorectal surgery and the methods and techniques of MB application. A further prospective clinical study is required.

Expressions of Collagen I and III in Hypoxic Keloid Tissue.

BACKGROUND: Wound heals itself spontaneously as physiological process. However, in some individuals, small wounds such as parenteral injections or body piercings may cause increased expression of collagen synthesis. The condition is known as keloid. Histopathology of keloid demonstrates extensive tissue proliferation that extends beyond the margin of primary wound. As a result, it develops uncontrolled or excessive fibrogenesis and tremendous source of collagen that still causes clinical problems until now. A wound, no matter how small the size is, will be followed by increased expression of collagen synthesis. Procollagen I and III is one of markers indicating the development of fibrosis. In fibrosis, there is hypoxia, which is characterized by stabilization of HIF-1α. Therefore, our study was aimed to obtain information about expression of collagen I and III in hypoxic keloid tissue. METHOD: The study design was observational descriptive. Keloid specimens were obtained from biopsy and preputium skins as the control specimens were obtained from circumcision. There were 10 tissue specimens for each specimen group. The analysis performed were evaluation of mRNA expression on collagen I, collagen III and HIF-1α using RT-PCR, the evaluation of HIF-1α protein level using ELISA and the expression of collagen I and collagen III protein using immunohistochemistry. Statistically, data was analyzed by unpaired t-test. RESULTS: In keloid with excessive cell proliferation, we found that the expression of procollagen I mRNA increased 35 times and the expression of procollagen III mRNA increased 27.1 times compared to preputium control group (p<0.05). The expression of procollagen I protein in the dermal layer of keloid was 61% and in the preputium was 37% (p<0.05). The expression of collagen III protein in the dermal layer of keloid was 39% and in the preputium was 16% (p<0.05). There was a 5-fold increase on expression of HIF-1α mRNA in keloid tissue compared to those in preputium (p<0.05). The levels of HIF-1α protein in keloid tissue was 0.201 ng/mg protein and the level in preputium was 0.122 ng/mg protein (p<0.05). There was a strong positive and extremely significant correlation between the expression of HIF-1α protein and procollagen III (R=0.744; p<0.05, Pearson), but HIF-1α with procollagen I are weak correlation (R=0.360; p>0.05, Pearson) Conclusion: Expression of collagen I and III have important role in hypoxic keloid tissue characterized by increased expressions. The expression of collagen I and III is associated with stable HIF-1α in keloid tissue.