A focus on intra-abdominal infections

Complicated intra-abdominal infections are an important cause of morbidity and are frequently associated with poor prognosis, particularly in higher risk patients

Antimicrobial resistance and antimicrobial stewardship in a Hong Kong teaching hospital.

Thilani Indunika Udayanthi Ahangama Marasinghe.Thesis (M.Phil.)--Chinese University of Hong Kong, 2008.Includes bibliographical references (leaves 156-168).Abstracts in English and Chinese.ABSTRACT (ENGLISH VERSION) --- p.IABSTRACT (CHINESE VERSION) --- p.IVDECLARATION --- p.VIACKNOWLEDGEMENTS --- p.VIITABLE OF CONTENTS --- p.IXLIST OF TABLES --- p.XIIILIST OF FIGURES --- p.XVILIST OF APPENDICES --- p.XVIIILIST OF ABBREVIATIONS --- p.XIXChapter CHAPTER 1 - --- INTRODUCTION --- p.1Chapter 1.1 --- Antimicrobial resistance --- p.1Chapter 1.1.1 --- Global emergence of drug-resistant organisms --- p.1Chapter 1.1.2 --- Resistance problem in Hong Kong --- p.5Chapter 1.1.2.1 --- Antimicrobial resistance of bacterial isolates in hospital --- p.5Chapter 1.1.2.2 --- Antimicrobial resistance of bacterial isolates from community --- p.8Chapter 1.1.3 --- Dynamics of resistance --- p.11Chapter 1.1.4 --- Mechanisms of antimicrobial resistance --- p.12Chapter 1.1.4.1 --- Enzymatic inactivation or modification --- p.12Chapter 1.1.4.2 --- Alteration of target site --- p.13Chapter 1.1.4.3 --- Impaired permeability --- p.13Chapter 1.1.4.4 --- Efflux pumps --- p.14Chapter 1.1.4.5. --- Alteration of metabolic pathway --- p.14Chapter 1.1.5 --- Association between antimicrobial use and resistance --- p.16Chapter 1.1.6 --- Clinical and economic impact of resistance --- p.17Chapter 1.1.7 --- Measures to minimize resistance in healthcare setting --- p.19Chapter 1.2 --- Antimicrobial classes --- p.21Chapter 1.2.1 --- β-Lactams --- p.21Chapter 1.2.2 --- Glycopeptides --- p.23Chapter 1.2.3 --- Quinolones --- p.24Chapter 1.2.4 --- Oxazolidinones-Linezolid --- p.25Chapter 1.3 --- Antimicrobial Stewardship Program (ASP) --- p.26Chapter 1.3.1 --- Definition --- p.26Chapter 1.3.2 --- Strategies --- p.27Chapter 1.3.3 --- Multidisciplinary Antimicrobial Management Team --- p.29Chapter 1.3.4 --- Limitations --- p.30Chapter 1.3.5 --- Experience in ASP --- p.30Chapter 1.4 --- ASP in Hong Kong --- p.36Chapter 1.4.1 --- Implementation at Prince of Wales Hospital --- p.36Chapter 1.4.2 --- Targeted antimicrobials --- p.38Chapter 1.5 --- Extended-Spectrum β-Lactamases (ESBLs) --- p.40Chapter 1.5.1 --- Classification of β-lactamases --- p.40Chapter 1.5.2 --- Definition of ESBLs --- p.42Chapter 1.5.3 --- Types of ESBLs --- p.42Chapter 1.5.4 --- Epidemiology of ESBLs --- p.44Chapter 1.5.5 --- ESBL detection --- p.46Chapter 1.5.6 --- Risk factors for acquisition of ESBL-producing organisms --- p.49Chapter 1.5.7 --- Clinical and economic impact of infections caused by ESBL- producing organisms --- p.50Chapter 1.5.8 --- Treatment options for infections caused by ESBL-producing organisms --- p.51Chapter 1.5.8.1 --- Carbapenems --- p.52Chapter 1.5.8.2 --- Noncarbapenems --- p.54Chapter 1.5.8.2.1 --- "Quinolones, aminoglycosides and sulfonamides" --- p.54Chapter 1.5.8.2.2 --- Cephalosporins --- p.55Chapter 1.5.8.2.3 --- β-Lactam/β-lactamase inhibitor combinations --- p.56Chapter 1.6. --- Objectives of the study --- p.58Chapter CHAPTER 2 - --- METHODS --- p.60Chapter 2.1 --- Data collection --- p.60Chapter 2.2 --- ESBL detection at PWH --- p.60Chapter CHAPTER 3 - --- OBJECTIVE 1 --- p.62Chapter 3.1 --- Title:-The impact of an Antimicrobial Stewardship Program on broad spectrum antimicrobials within a Medical Department in a Hong Kong tertiary care hospital --- p.62Chapter 3.2 --- Method --- p.62Chapter 3.2.1 --- Study setting --- p.62Chapter 3.2.2 --- Study design and sample --- p.62Chapter 3.2.3 --- Definitions --- p.63Chapter 3.2.4 --- Data collection --- p.64Chapter 3.2.5 --- Data analysis --- p.65Chapter 3.2.5.1 --- Outcome measures --- p.65Chapter 3.2.5.2 --- Statistical analysis --- p.65Chapter 3.3 --- Results --- p.66Chapter 3.3.1 --- Patient characteristics --- p.66Chapter 3.3.2 --- Clinical characteristics --- p.66Chapter 3.3.2.1 --- Source of infection --- p.66Chapter 3.3.2.2 --- Severity of infection-Intervention period --- p.69Chapter 3.3.2.3 --- Healthcare-associated infections (HAIs) --- p.69Chapter 3.3.3 --- Prescribing practices --- p.71Chapter 3.3.3.1 --- Prescriptions reviewed and pattern of antibiotic prescription --- p.71Chapter 3.3.3.2 --- Indication --- p.73Chapter 3.3.3.2.1 --- Appropriateness of indication --- p.73Chapter 3.3.3.2.2 --- Appropriate indications of use-Individual targeted antimicrobials --- p.75Chapter 3.3.3.2.3 --- Inappropriate antimicrobial use --- p.77Chapter 3.3.4 --- Recommendations made and acceptance --- p.79Chapter 3.3.5 --- Outcome measures --- p.81Chapter 3.3.5.1 --- Multivariate model of appropriate antimicrobial use --- p.81Chapter 3.3.5.2 --- Multivariate model of all-cause mortality --- p.82Chapter 3.3.5.3 --- Treatment outcome-intervention period --- p.85Chapter 3.3.6 --- Antimicrobial consumption --- p.86Chapter 3.3.6.1 --- Targeted antimicrobials --- p.86Chapter 3.3.6.2 --- Other antimicrobials --- p.86Chapter 3.3.7 --- Bacterial susceptibility --- p.89Chapter 3.3.7.1 --- Escherichia coli --- p.89Chapter 3.3.7.1.1 --- Resistance rates to amoxicillin/clavulanate --- p.89Chapter 3.3.7.1.2 --- ESBL-producing Escherichia coli --- p.89Chapter 3.3.7.2 --- Methicillin resistant-Staphylococcus aureus (MRSA) --- p.92Chapter 3.3.7.3 --- Pseudomonas aeruginosa --- p.93Chapter 3.3.7.3.1 --- Susceptibility rates to targeted antimicrobials --- p.93Chapter 3.3.7.3.2 --- Susceptibility rates to other antimicrobials --- p.93Chapter 3.4 --- Discussion --- p.97Chapter 3.4.1 --- Background characteristics of patients who were prescribed targeted antimicrobials --- p.97Chapter 3.4.2 --- Healthcare-associated infections (HAIs) --- p.98Chapter 3.4.3 --- Impact of ASP on appropriateness of antimicrobial prescription --- p.99Chapter 3.4.4 --- Compliance to recommendations --- p.101Chapter 3.4.5 --- Clinical impact of ASP --- p.101Chapter 3.4.6 --- Impact of ASP on antimicrobial consumptions --- p.103Chapter 3.4.7 --- Impact of ASP on antimicrobial resistance --- p.105Chapter 3.4.8 --- Influential factors associated with appropriate antimicrobial use --- p.108Chapter 3.4.9 --- Limitations --- p.109Chapter 3.4.10 --- Areas for further evaluation --- p.111Chapter CHAPTER 4 - --- OBJECTIVE II --- p.114Chapter 4.1 --- Title:-Treatment outcome and factors affecting treatment outcome of patients with bacteremia due to extended-spectrum β-lactamases-producing organisms receiving carbapenems or β-lactam/β-lactamase inhibitor combinations --- p.114Chapter 4.2 --- Method --- p.114Chapter 4.2.1 --- Study setting --- p.114Chapter 4.2.2 --- Study design and sample --- p.114Chapter 4.2.3 --- Definitions --- p.115Chapter 4.2.4 --- Data collection --- p.117Chapter 4.2.5 --- Data analysis --- p.118Chapter 4.2.5.1 --- Outcome measures: --- p.118Chapter 4.2.5.2 --- Statistical analysis: --- p.118Chapter 4.3 --- Results --- p.119Chapter 4.3.1 --- Patient characteristics --- p.120Chapter 4.3.2 --- Predisposing factors --- p.120Chapter 4.3.3 --- Clinical characteristics --- p.122Chapter 4.3.3.1 --- Type and source of infection --- p.123Chapter 4.3.3.2 --- Severity of illness markers --- p.123Chapter 4.3.4 --- Outcome measures --- p.125Chapter 4.3.4.1 --- Treatment outcome and reasons for therapeutic failure --- p.125Chapter 4.3.4.2 --- Factors associated with therapeutic failure --- p.127Chapter 4.3.4.2.1 --- Univariate analysis of variables to be associated with therapeutic failure --- p.127Chapter 4.3.4.2.2 --- Multivariate model of treatment failure --- p.129Chapter 4.3.4.3 --- Factors associated with all-cause mortality --- p.130Chapter 4.3.4.3.1 --- Univariate analysis of variables to be associated with all-cause mortality --- p.130Chapter 4.3.4.3.2 --- Multivariate model of all-cause mortality --- p.133Chapter 4.3.5 --- Subgroup analysis --- p.134Chapter 4.3.5.1 --- Carbapenem versus Cefoperazone/sulbactam --- p.134Chapter 4.3.5.2 --- Carbapenem versus Piperacillin/tazobactam --- p.141Chapter 4.3.5.3 --- Carbapenem versus Amoxicillin/clavulanate --- p.144Chapter 4.3.5.4 --- Comparison of treatment outcome --- p.147Chapter 4.4 --- Discussion --- p.148Chapter 4.4.1 --- Predisposing factors --- p.148Chapter 4.4.2 --- Treatment outcome --- p.149Chapter 4.4.3 --- Limitations and areas for further study --- p.153Chapter CHAPTER 5 - --- CONCLUSIONS --- p.154REFERENCES --- p.156APPENDICES --- p.16

Antimicrobial Treatmdent of "Complicated" Intra-Abdominal Infections and The New IDSA Guidelines - A Commentary and an Alternative European Approach According to Clinical Definitions

Recently, an update of the IDSA guidelines for the treatment of complicated intraabdominal infections has been published. No guideline can cater for all variations in ecology, antimicrobial resistance patterns, patient characteristics and presentation, health care and reimbursement systems in many different countries. In the short time the IDSA guidelines have been available, a number of practical clinical issues have been raised by physicians regarding interpretation of the guidelines. The main debatable issues of the new IDSA guidelines are described as follows

Defining the Aetiology and Antimicrobial Susceptibility Patterns of the Predominant Bacteria Associated with Bloodstream Infections at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam

Bloodstream infections (BSI) are among the most common critical diseases that require intensive care and continuous surveillance. According to many multinational antimicrobial resistance surveillance schemes, Asia represents a substantial reservoir of clinically relevant antimicrobial resistant genes. These genes include extended spectrum Beta lactamases (ESBLs) and AmpC lactamases in the Enterobacteriaceae, methicillin-resistance genes in Staphylococcus aureus, carbapenemase-resistance genes in Gram-negative bacilli and vancomycin-resistance genes in enterococcus. Asian countries are also burdened with high prevalence of HIV, in which BSI can be a major health problem in these immunocompromised people. Currently, there are no national data regarding the pathogens associated with BSI in Vietnam. Additionally, there are limited BSI data in specific populations, such as those infected with HIV, and there is limited information regarding the distribution and epidemiology of hospital-acquired and community-acquired infections. Data contributing to our understanding of common antimicrobial resistance mechanisms or profiles, including ESBLs, AmpC, KPC, and MRSA in BSI pathogens in Vietnam are also scarce. The aims of this study were to describe the characteristics of BSI in the Hospital for Tropical Diseases (HTD), a tertiary healthcare facility for infectious diseases in the south of Vietnam. I aimed to identify the most common BSI pathogens and their antimicrobial resistance profile in the context of the aetiological agent and disease outcome. Further, I aimed to define the specific types of ESBLs and AmpC genes circulating in Gram-negative bacilli isolated from BSI patients. I further describe the clinical and laboratory characteristics of BSI infections caused by the non-typhoidal Salmonella (iNTS) a particular group of BSI pathogens that are prevalent in immunocompromised patients. Lastly, I aimed to validate an automatic antimicrobial susceptibility testing system for Salmonella isolates in comparison to manual testing methods. I found that BSI in HTD was characterised by a low annual blood culture positivity rate (7%) and a declining annual trend of mortality. A high proportion of BSI was from patients in the intensive care unit (33%) and the HIV ward (22%). I report an increased trend of multidrug-resistant Gram-negative and Gram-positive pathogens in both hospital-acquired and community-acquired BSI infections. I additionally report a case study for BSI due to Vibrio cholerae non-O1, non-O139 and the first-ever outbreak report of Brucella melitensis in Vietnam. I performed molecular characterisation for all Gram-negative organisms isolated over a four-year period that exhibited reduced susceptibility against 3rd cephalosporin. Phenotypic screening found 304/1,017 (30%) organisms that were resistance to third generation cephalosporins; 172/1017 (16.9%) of isolates exhibited ESBL activity, 6.2% (63/1017) had AmpC activity, and 0.5% (5/1017) had both ESBL and AmpC activity. E. coli and Aeromonas spp. were the most common organisms associated with ESBL and AmpC phenotypes, respectively. There was no significant difference (p>0.05) between antimicrobial resistance phenotypes of organisms associated with community and hospital-acquired infections. I retrospectively identified 102 cases of iNTS infections in HTD between 2008 and 2013. Of 102 iNTS patients, 71% were HIV-infected, >90% were adults, 71% were male, and 33% reported intravenous drug use. Twenty-six/92 (28%) patients with a known outcome died; HIV infection was significantly associated with death (p=0.039). S. Enteritidis (Sequence Type (ST)11) (48%, 43/89) and S. Typhimurium (ST19, 34 and 1544) (26%, 23/89) were the most commonly identified serovars; S. Typhimurium was significantly more common in HIV-infected individuals (p=0.003). Through comparison of different antimicrobial testing methods for Salmonella, I identified a problematic agreement or errors were with quinolone antimicrobials. I found that the VITEK automatic antimicrobial susceptibility testing system did not produce satisfactory results for the Salmonella. However, the disk-diffusion method was a more reliable method for testing beta-lactams, azithromycin, and trimethoprim-sulfamethoxazole. In conclusion, BSI in HTD are characterised with an increasing trend of multi-drug resistant organisms that will challenge clinical and laboratory diagnostic as and future treatment options

THE PREVALENCE OF EXTENDED SPECTRUM BETA-LACTAMASE (ESBL) IN THIRD GENERATION CEPHALOSPORIN USAGE AMONG SEPSIS PATIENTS IN THE DEPARTMENT OF INTERNAL MEDICINE RSUD DR. SOETOMO SURABAYA

ABSTRAK Insiden sepsis maupun kematian akibat sepsis terus meningkat setiap tahunnya. Antibiotika golongan beta-laktam paling banyak digunakan untuk mengatasi berbagai jenis infeksi. Banyaknya penggunaan antibiotika tersebut mengakibatkan munculnya enzim Extended Specrtum ß-lactamase (ESBL Kata kunci: Extended Spectrum Beta-Lactamase (ESBL), sefalosporin generasi ketiga, sepsis, RSUD Dr Soetomo ABSTRACT The incidence of sepsis and death caused by sepsis increases each year. Beta-lactam antibiotics is widely used to treat many types of infections because of its minimum side-effects. As a result of the widespread use of broad spectrum cephalosporin, an Extended Spectrum ß-lactamase (ESBL) enzyme produced by K. ozaenae has developed. Since then, other types of ESBL have been found and spread around the world relatively fast. The prevalence of infection caused by ESBL-producing bacteria varies in each country. In Indonesia, the incidence of ESBL in Enterobacteriaceae is still not widely known. This research aims to investigate the prevalence of ESBL in third generation cephalosporin usage among sepsis patients i

Klebsiella pneumoniae bloodstream infections in hospitalised children at Red Cross War Memorial Children's Hospital : 2006 - 2011

Background: Klebsiella pneumoniae (KP) is a significant paediatric bloodstream pathogen in children. There is little data about KP in South African children. The focus for the present study was to address this knowledge gap. Methods: This study addressed a retrospective case notes review on bloodstream Klebsiella pneumoniae infections at a children's hospital in Cape Town, South Africa 2006-2011 using conventional descriptive and comparative statistical methods. Results: Of 410 hospitalised children with laboratory confirmed KP bloodstream infection (KPBSI), 339 (83%) were presumed extended-spectrum β-lactamase (ESBL) producing isolates. The median age (interquartile range, IQR) was 5.0 (2-16) months, 212 (51.7%) were male, 82 (20%) were HIV-infected, and 241 (58.8%) were moderately or severely underweight. The infection was nosocomial or healthcare-associated in 389 (95%) children and community-acquired in 21 (5%) children. Significant risk factors for the acquisition of ESBL-KP bloodstream infection included cephalosporin exposure in the preceding 12 months prior to the KPBSI p=<0.0001: aRR 1.25 (95% CI: 1.15-1.36); and those who had intravenous infusions for more than 3 days prior to the KPBSI, p=0.004: aRR 1.18 (95% CI: 1.05-1.31)

The management of intra-abdominal infections from a global perspective : 2017 WSES guidelines for management of intra-abdominal infections

Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in the emergency departments worldwide. The cornerstones of effective treatment of IAIs are early recognition, adequate source control, and appropriate antimicrobial therapy. Prompt resuscitation of patients with ongoing sepsis is of utmost important. In hospitals worldwide, non-acceptance of, or lack of access to, accessible evidence-based practices and guidelines result in overall poorer outcome of patients suffering IAIs. The aim of this paper is to promote global standards of care in IAIs and update the 2013 WSES guidelines for management of intra-abdominal infections.Peer reviewe

Bactericidal and Bacteriostatic Antibiotics

Of all the medications available to physicians worldwide, antibiotics play an essential role in inpatient and outpatient settings. Discovered in the early nineteenth century by Alexander Fleming, penicillin was the first antibiotic isolated from a mold. Dr. Gerhard Domagk developed synthetic sulfa drugs by altering the red dye used in chemical industries. Since then, multiple antibiotic classes have been discovered with varying antimicrobial effects enabling their use empirically or in specific clinical scenarios. Antibiotics with different mechanisms of action could be either bactericidal or bacteriostatic. However, no clinical significance has been observed between cidal and static antibiotics in multiple trials. Their presence has led to safer deep invasive surgeries, advanced chemotherapy in cancer, and organ transplantation. Indiscriminate usage of antibiotics has resulted in severe hospital-acquired infections, including nosocomial pneumonia, Clostridioides difficile infection, multidrug-resistant invasive bacterial infections, allergic reactions, and other significant side effects. Antibiotic stewardship is an essential process in the modern era to advocate judicial use of antibiotics for an appropriate duration. They play a vital role in medical and surgical intensive care units to address the various complications seen in these patients. Antibiotics are crucial in severe acute infections to improve overall mortality and morbidity