This presentation discusses tackling multiple drug resistant organisms (MDROs) from an intensive care perspective. It notes that intensive care faces the consequences of therapeutic misadventures upstream. The document outlines various definitions of MDROs such as MRSA, VRE, and ESBL gram negatives. It discusses how antibiotic resistance is inevitable due to the power of bacteria and natural selection. Higher antibiotic use correlates with higher resistance rates, particularly in inpatient settings like ICUs. ESBL and other resistant organisms are increasingly prevalent in developing world ICUs compared to developed countries. Studies also show ESBL and VRE infections are associated with higher mortality and costs.
Description of the major classes of antimicrobial drug, resistant mechanisms developed by bacteria to combat the action of antimicrobials, and the control measures needed to limit this horizontal gene transfer.
To study Prevalence, Pre-disposing factors and Prevention of the following MDRO’s – Klebsiella pneumoniae Carbapenemase Producer, Methicillin Resistant Staphylococcus aureus, Multi Drug Resistant Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli.
Description of the major classes of antimicrobial drug, resistant mechanisms developed by bacteria to combat the action of antimicrobials, and the control measures needed to limit this horizontal gene transfer.
To study Prevalence, Pre-disposing factors and Prevention of the following MDRO’s – Klebsiella pneumoniae Carbapenemase Producer, Methicillin Resistant Staphylococcus aureus, Multi Drug Resistant Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli.
Ventilator Associated Pneumonia (VAP) causes and preventive strategiesVeera Reddy Suravaram
Ventilator associated pnemonia is a cause of concern in today's medical practice due to wide spread of Gram negative pathogens in hospitals and lack of good hygienic practices due to high occupancy rate in ICUs.
Infection Control and Antibiotic Stewardship Symposia presented in Milot, Haiti at Hôpital Sacré Coeur.
CRUDEM’s Education Committee (a subcommittee of the Board of Directors) sponsors one-week medical symposia on specific medical topics, i.e. diabetes, infectious disease. The classes are held at Hôpital Sacré Coeur and doctors and nurses come from all over Haiti to attend.
This presentation is the gist of hospital infection control. Has touched all important policies and parameters involved in infection control in a healthcare settings in brief.
Malignant Mixed Mullerian Tumor – Case Reports and Review ArticleApollo Hospitals
Malignant mixed mullerian tumors are very rare genital tumors. They are biphasic neoplasms composed of an admixture of malignant epithelial and mesenchymal elements. In descending order of frequency they originate in the uterus, ovaries, fallopian tubes, cervix and vagina. Also they arise denovo from peritoneum. They are highly aggressive and tend to occur in postmenopausal low parity women. Because of rarity, there is as such no treatment guidelines available. Multimodality treatment in the form of radical surgery followed by adjuvant chemotherapy or radiotherapy or combined chemoradiation gives a better prognosis & outcome. Two case reports of such tumors, one from ovary and other from penitoneum are presented along with the review of literature.
Ventilator Associated Pneumonia (VAP) causes and preventive strategiesVeera Reddy Suravaram
Ventilator associated pnemonia is a cause of concern in today's medical practice due to wide spread of Gram negative pathogens in hospitals and lack of good hygienic practices due to high occupancy rate in ICUs.
Infection Control and Antibiotic Stewardship Symposia presented in Milot, Haiti at Hôpital Sacré Coeur.
CRUDEM’s Education Committee (a subcommittee of the Board of Directors) sponsors one-week medical symposia on specific medical topics, i.e. diabetes, infectious disease. The classes are held at Hôpital Sacré Coeur and doctors and nurses come from all over Haiti to attend.
This presentation is the gist of hospital infection control. Has touched all important policies and parameters involved in infection control in a healthcare settings in brief.
Malignant Mixed Mullerian Tumor – Case Reports and Review ArticleApollo Hospitals
Malignant mixed mullerian tumors are very rare genital tumors. They are biphasic neoplasms composed of an admixture of malignant epithelial and mesenchymal elements. In descending order of frequency they originate in the uterus, ovaries, fallopian tubes, cervix and vagina. Also they arise denovo from peritoneum. They are highly aggressive and tend to occur in postmenopausal low parity women. Because of rarity, there is as such no treatment guidelines available. Multimodality treatment in the form of radical surgery followed by adjuvant chemotherapy or radiotherapy or combined chemoradiation gives a better prognosis & outcome. Two case reports of such tumors, one from ovary and other from penitoneum are presented along with the review of literature.
Intra-Fetal Laser Ablation of Umbilical Vessels in Acardiac Twin with Success...Apollo Hospitals
To interrupt blood supply to the acardiac twin in a case of TRAP sequence of monochorionic diamniotic multiple pregnancy to allow for continuation of the normal twin.
Breast Cancer in Young Women and its Impact on Reproductive FunctionApollo Hospitals
Breast cancer is the most common cancer in women in developed countries. Chemotherapy for breast cancer is likely to negatively impact on reproductive function. We review current treatment; effects on reproductive function; breastfeeding and management of menopausal symptoms following breast cancer.
Turner syndrome (gonadal dysgenesis) is one of the most common chromosomal abnormalities occuring 1 in 2500 to 1 in 3000 live-born girls. It is an important cause of short stature in girls and primary amenorrhea in young women that is usually caused by loss of part or all of an X chromosome. This review briefly summarises the current knowledge about the syndrome and the management strategies.
Due to pregnancy thyroid economy is affected with changes in iodine metabolism, TBG and development of maternal goiter. The incidence of hypothyroidism in pregnancy is quite common with autoimmune hypothyroidism being the most important cause. Overt as well as subclinical hypothyroidism has a varied impact on maternal and neonatal outcome. After multiple studies also, routine screening in pregnancy for hypothyroidism can still not be recommended. Management mainly comprises of dosage adjustments as soon as pregnancy is diagnosed based on results of thyroid function tests. The aim should be to keep FT4 at the upper end of normal range.
Growth Hormone Deficiency (GHD) can persist from childhood or be newly acquired. Confirmation through stimulation testing is usually required unless there is a proven genetic/structural lesion persistent from childhood. Growth harmone (GH) therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD. The risks of GH treatment are low. GH dosing regimens should be individualized. The final decision to treat adults with GHD requires thoughtful clinical judgment with a careful evaluation of the benefits and risks specific to the individual.
Advances in the management of thalassemia have led to marked improvements in the life span and quality of life of children and young adults. This poses new challenges for the treating physicians. There is now increasing recognition that thalassemics have impaired bone health which is multifactorial in etiology. This paper aims to highlight the factors that predispose these patients to osteoporosis and suggests measures to minimise the impact on bone health.
Laparoscopic Excision of Foregut Duplication Cyst of StomachApollo Hospitals
Retroperitoneal gastric duplication cysts lined by ciliated columnar epithelium are extremely rare lesions and its presentation during adulthood is a diagnostic challenge for treating clinicians. This entity often resembles cystic pancreatic neoplasm, retroperitoneal cystic lesions and sometimes as an adrenal cystic neoplasm. Correct diagnosis on the basis of radiological investigation is difficult and histopathologic analysis. We report a case of gastric duplication cyst in a 16year old girl that mimicked as a retroperitoneal /pancreatic /adrenal cystic lesion and was successfully managed by laparoscopy.
Occupational Blood Borne Infections: Prevention is Better than CureApollo Hospitals
Viral infections like HIV, hepatitis Band C virus pose a big risk to the contacts of individuals with high risk behaviour as well as to the attending health care workers. Blood, semen, vaginal and other potentially infectious materials can transmit the infection to the susceptible contacts. Universal precautions should be strictly implemented during clinical examination, laboratory work and surgical procedures to prevent transmission to the health care providers. Health care workers should receive vaccination for hepatitis B infection. An inadvertent exposure should be managed with proper first aid and infectivity of the source and severity of exposure should be assessed. Severity of exposure is based on the nature and area of exposed surface, mode of injury and volume of infective material. Post-exposure prophylaxis (PEP) should be started as soon as possible after a proper counseling about the effectiveness of post-exposure prophylaxis, side effects and risk of carrying the infection to his familial contacts and its prevention.
Evaluation of Red Cell Hemolysis in Packed Red Cells During Processing and St...Apollo Hospitals
Storage of red cells causes a progressive increase in hemolysis. Inspite of the use of additive solutions for storage and filters for leucoreduction some amount of hemolysis is still inevitable. The extent of hemolysis however should not exceed the permissible threshold for hemolysis even on the 42nd day of storage.
Efficacy and safety of dexamethasone cyclophosphamide pulse therapy in the tr...Apollo Hospitals
Various drugs used to treat pemphigus can cause remission, but none can provide permanent remission as relapses are common. With the introduction of DCP in pemphigus in 1984, patients started being in prolonged/permanent remission. This study was done to compare the efficacy of DCP to oral corticosteroids and cyclophosphamide in combination.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)Apollo Hospitals
Severe skin adverse drug reactions can result in death. Toxic epidermal necrolysis (TEN) has the highest mortality (30–35%); Stevens-Johnson syndrome and transitional forms correspond to the same syndrome, but with less extensive skin detachment and a lower mortality (5–15%). Hypersensitivity syndrome, sometimes called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), has a mortality rate evaluated at about 10%. It is characterised by fever, rash and internal organ involvement. Prompt diagnosis is vital, along with identification and early withdrawal of suspect medicines and avoidance of re-exposure to the responsible agent is essential. Cross-reactivity to structurally-related syndrome caused by Carbamazepine medicines is common, thus first-degree relatives may be predisposed to developing this syndrome. We report a case of DRESS secondary to use of Carbamazepine.
Difficult Laparoscopic Cholecystectomy-When and Where is the Need to Convert?Apollo Hospitals
Laparoscopic cholecystectomy has now become the treatment of choice for the gall bladder stone. With increasing experience, surgeon has started to take more difficult cases which were considered relative contra indications for laparoscopic removal of gall bladder few years back.
We conducted this study at our hospital and included all laparoscopic cholecystectomy done from May'08 to January'10. Total time taken in surgery, conversion rate and complication rate were analysed. Factors making laparoscopic cholecystectomy difficult were also analysed. We defined difficult laparoscopic cholecystectomy when we found -dense fibrotic adhesions in and around Callot's triangle, gangrenous gall bladder, empyma, large stone impacted at gall bladder neck, contracted gall bladder, Mirrizi's syndrome, h/o biliary pancreatitis, CBD stones, acute cholecystitis of <72 hrs duration.
Out of 206 cases done during above period, 56 cases were considered difficult. Only two cases were converted to open.
With growing experience and technical advancement surgery can be completed in most of the difficult cases. This is important because recently it is shown in literature that laparoscopic cholecystectomy is associated with less morbidity than open method irrespective of duration of the surgery.
Deep vein thrombosis prophylaxis in a tertiary care center: An observational ...Apollo Hospitals
Deep vein thrombosis (DVT) is a major health problem with substantial mortality and morbidity in medically ill patients. Prevention of DVT by risk factor stratification and subsequent antithrombotic prophylaxis in moderate- to severe-risk category patients is the most rational means of reducing morbidity and mortality.
The spread of dengue and dengue haemorrhagic fever is increasing, atypical manifestations are also on the rise, although they may be under reported because of lack of awareness. We report two such cases of dengue hemorrhagic fever with hepatitis, intraocular hemorrhage, ARDS and myocarditis.
A 71-year-old male presented in ENT department with dysphagia for last three weeks, more to solids than liquids. He had a hard bony bulge in the posterior pharyngeal wall on palpation and hence was referred for an Orthopaedic opinion. Lateral radiograph of the cervical spine revealed diffuse ossification of the anterior longitudinal ligament. This ossification was extending almost half the width of the cervical body from its anterior body at C1 and C2 vertebra level.
Pediatric Liver Transplant (LT) is now an established procedure for End Stage Liver Disease (ESLD) with biliary atresia being the commonest indication. Intensive pre-transplant evaluation, nutritional buildup and immunization are the fundamental pre-requisites of a successful LT. With improvement in surgical micro-anastomotic techniques and superior immunosuppressive regimens the success rate of pediatric LT is in excess of 90%. Most of the transplants in our country however are Living related, due to which a fairly large number of children expire awaiting a donor liver. There should be a concerted effort to evolve the cadaveric donation program, so that majority of the children are benefitted.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
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Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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How to Give Better Lectures: Some Tips for Doctors
MDRO Strategies
1. This presentation was presented at Apollo
International Forum on Infection Control (AIFIC’
2013), Chennai
The presentation is solely meant for Academic purpose
3. Disclaimer:
My Perspective
I have neither the
intellectual depth
nor
the luxury of the
remote academic view
that ID specialists or
clinical microbiologists
may have……
4. Intensive Care…
….is a “downstream” speciality…
…we face the consequences of
many therapeutic misadventures!!!
5. MDRO Definition
“Micro-organisms (predominantly bacteria)
that are resistant to one or more classes of
anti-microbial agents
MRSA
VRE
ESBL Gram negatives
“Pan-resistant” Acinetobacter
KPC- Klebsiella pneumoniae
VIM-2 / NDM-1 Klebsiella pneumoniae
Stenotrophomonas
Assault of the Acronym
Burkholderia
VISA
VRSA…..
7. …& the “Power of Bacteria”…
(Historical & Numerical = Genetic)
Age:
Bacteria 3,500,000,000 years (2000x) = 1yr
Eukaryotes 1,800,000,000 years (1000x)
Multi-cellulars 580,000,000 years (300x)
Australopithecus 4,000,000 years (2x)
Homo erectus <2,000,000 years (1) = 5.2 hrs
Antibiotic use 60 years (0.00003x) = 55 secs
Numbers:
“ The number of E. Coli in the gut of each human being far
exceed the number of people that now live or have ever
inhabited the earth” !!!
- Gould SJ; Life’s Grandeur
8. …antibiotic resistance is Inevitable !
Penicillin Methicillin
Penicillin-resistant Methicillin-resistant
S. aureus S. aureus S. aureus
[1950s] [1970s] (MRSA)
Vancomycin
[1997] [1990s]
Vancomycin Vancomycin-
Vancomycin- intermediate- resistant
resistant resistant enterococci (VRE)
[2002] S. aureus
S. aureus
(VISA / GISA)
9. Selection of Resistance
Antibiotic
exposure
Resistant strains: rare Resistant strains:
No survival advantage dominant
10. Use Promotes Resistance
Urinary E. Coli Resistance vs. Antibiotic Use
Usage (DDD/1000/day)
% Resistance
Antibiotic use is a strong Correlate of Resistance
JAC; DOI: 10.1093/ jac /dkg488 (but not the only factor)
11. Antibiotics & Resistance
50 p <0.01 for all
45 comparisons
% Resistant Organisms
40
35
Evidence:
30 Inpatient
Resistant organisms are 25 Outpatient
more common amongst
inpatients 20
15
ICUs (with highest use) 10
have highest rates of 5
resistance 0
SA
Z
SE
E
CT
VR
MR
MR
e ud
Ps
Archibald et al; ICARE Widespread use of antibiotics leads to the
Clin Inf Dis 1997; 24: 211-15 selection of antibiotic resistant strains
15. ESBL in the Developing World
Site Location %ESBL
Klebsiella E. coli
AIIMS, New Delhi1 Tertiary Hospital 80% -
Mathai 10 Tertiary Hosps. - >60%
KGMC, Lucknow2 Neonatal ICU 86% 64%
SMF, Chennai Nosocomial: ICU 84% 82%
SMF, Chennai Comm. Acquired: ICU 53% 44%
China, Shanghai3 University Hospital 51% 24%
Latin America4 SENTRY, Pneumonia 44% 29%
1: Ind J Med Res 2002;115:153-7 2: J Med Microb 2003; 52: 421-5 3: Zhou Yi Xue Za Zhi 2002;82:1476-9 4: Diag Mic Inf Dis 2002; 44: 301-11
16. Developing World ICUs
International Nosocomial Infection Control
Consortium (INICC)
8 Countries; 55 ICUs; 46 Hospitals
NNIS (USA) INICC
1992-2004 2002-5
MRSA 59% 84%
ESBL 19% 55%
Quin. res Pseudo. 29% 59%
VRE 29% 5%
Ann Int Med 2006; 145: 582-91
17. Does ‘ESBL’ kill?
Case control study from Israel (198 patients)
Multivariate analysis;
ESBL remains independently associated
with
Mortality OR 3.6 (1.4 - 9.5) p <0.008
Delayed Rx OR 25.1 (10.5 - 60.2) p <0.001
LOS OR 1.56 p <0.001
Cost OR 1.57 p <0.003
Antimicrob Agents Chemo 2006; 50: 1257-62
18. VRE Implications: Mortality
Vancomycin Resistance is:
An independent predictor of death in
EC bacteremia (OR: 2.1; 95% CI:1.14-3.88)
Associated with J all cause mortality
(52% vs. 27% in vanco sensitive)
An independent predictor of infection
related death (OR: 5.2; 95% CI: 1.4-20.0)
Ann Int Med 2001; 135: 484-92
Diag Micr ID 2000; 36: 145-52
CID 2000; 30: 466-72
Newer studies (? more effective Rx) show
CID 2002; 34: 922-9 no difference
19. MRSA: Attributable Mortality
Debated with VAP*
Odds of death 2x with MRSA bacteremia vs. MSSA
Meta-analysis:
31 cohort studies
3963 patients
2/3 MSSA vs. 1/3
MRSA
Clin Inf Dis 2003; 36:53–9
*Anes Clin N A 2004: 22 ; 405 - 35
20. Risk Factors for MDRO
Age / co-morbidity
Severity of illness
ICU admission
Demographic
Prior Antibiotic exposure
Antibiotic / Prior colonization
infection control
Exposure to colonized/ infected patient
Procedural Invasive Device use
CID 2001; 33: 939-46
Inf Cont Hosp Epi 2009; 30: 1180-5
21. Approach to Preventing MDRO
Factors Early goal-directed
Severity of illness…. Rx
Device use Avoid Devices
Minimise
Antibiotic use
device-associated
infection
Cannot justify an
“I’m not to blame” Rational & conservative
attitude antibiotic use
22. CDC: Strategies
Is our empirical
strategy correct?
Administrative Support
What is the value of a
restricted formulary? Education
Antibiotic Use
Active Surveillance Culture
Culture vs. rapid detection? Isolation Precautions
Practicality? Environmental issues
Decolonization
Mupirocin & SDD?
24. Assumptions for use of
Empirical Antibiotics
Infection J (attributable) mortality
Antibiotic treatment K mortality
Early administration of correct antibiotic
is better than delayed administration
Adverse effects < the benefits of treatment
25. Attributable Mortality
Nosocomial Attributable
Infection mortality
Definition:
Mortality caused by an All Nosocomial Infection 20% (2.8-44)
infection (in excess of
mortality in a similarly ill Blood-stream 25% (4.4-47.3)
patient without infection).
Vent. Assoc. Pneumonia 25% (7.8-42)
Chest 2001; 120:2059–93 Urinary Tract None
26. Is death attributable to NI?
NI
Treat Don’t Treat
Is there a difference?
Yes No
NI kills Patient dies of
critical illness
Unethical to evaluate in this way!
27. Is death attributable to NI?
Cohort of ICU Patients
Definition:
Difference in death NI No NI
rates between
infected & uninfected
patients after adjusting Rx No (appropriate) Rx
for confounders
Severity of illness is a confounder;
May be adjusted by case-control studies
or Multivariate (regression) analysis
Ideally Propensity modeled
28. Effect of Appropriate Choice
100
90
Hospital Mortality (%)
80
70
60
50
40
30
20
10
0
Luna et al; No Rx Correct Rx Incorrect
Chest 1997; 111: 676-85.
29. Effect of Appropriate Timing
100
90
80
Hospital Mortality (%) 70
60
50
40
30
20
10
0
Luna et al; Early Late
Chest 1997; 111: 676-85. None Correct Incorrect
30. Methodological Issues
Systematic review of 51 studies of “appropriate
antibiotics” and mortality in bacteraemia
No distinction : Empirical vs. definitive
Only 16% (8) defined “appropriate” on the basis
of in-vitro Cx + route + dose
Only 35% looked at attributable mortality
Only 21% (7) timed severity of illness measures;
but 2 measured it at admission
33% (17) adjusted for septic shock
CID 2007; 45: 329 - 37 Only one study used Propensity scores
32. Making De-escalation
Possible
De-escalation is seldom attempted
Recent study of VAP*
De-escalation only in 22% patients
Likely to occur if:
3-4 antibiotics were initially used
If adequate cover was initially provided
If major pathogen grew on culture
*Chest 2006; 129:1210–1218 If culture method was more robust
33. Rational De-escalation?
Can we use sputum, BAL cytology &
culture to make decisions?
Probability of VAP +ve -ve
BAL with bacteria >95% 25-50%
Sputum culture 95% 45%
BAL culture 72-95% 50%
JAMA. 2007;297:1583-93 No!
34. Current Empirical Rx encourages
overuse
Suspected VAP
Rx
65% 35%
VAP No VAP
Appropriate Inappropriate ?
De-escalated No de-
escalation Colonization by resistant bugs
& subsequent adverse outcome
35. VAP: A Decision Analysis
A decision analysis based on available
data suggests:
Empirical Rx (using clinical diagnosis) :
66% mortality in the untreated patients
68% mortality in treated patients
Reasons for unexpected death with Rx:
Diagnostic certainty is low (0.23)
Uninfected pts colonize c resistant strains
Chest 1996; 110:1025-34 Limitations: Old data; incomplete info
37. Strategies to Reduce
Resistance
Cycling
Abx 1 Abx 2 Abx 3 Abx 1
Resistance
Time
Presumes that a decline in resistance will occur
with antibiotic cessation (ie, there is a ‘fitness cost’
to antibiotic resistance.)
38. Cycling: The Evidence?
None of the evidence is “clean”
Mainly observational cohorts
Gerding et al Some studies are of a single scheduled
AAC 1991; 35: 1284-90 change (not cycling)
Koleff et al
AJRCCM 1997; 156: 1040-8
Associated confounders:
Gruson et al
Antibiotic restriction policies
AJRCCM 2000; 162: 837-43 Infection prevention strategies
Raymond et al
CCM 2001; 29: 1101-8
Often evaulate nosocomial infection
alone not colonisation rates
Toltzis et al
Paediatrics 2002; 110: 707-11 RCTs are needed
39. Inefficacy of Cycling
Restriction, Rotation, ?Rubbish…
Abx 1 Abx 2 Abx 3 Abx 1
Resistance
The rate of decline of resistance will depend on:
the cycling interval &
Proc Nat Ac Sci 1999; 96:1152-56 the fitness cost of antibiotic resistance
40. Mathematical Models
Model simulating hospital patients / NI
Bergstrom & Reluga:
Cycling and mixing are better than one drug
Non-optimal strategies of cycling or mixing
degrade effect
Even in optimal conditions cycling is not much
better than mixing
“Cycling is unlikely to reduce either the
evolution or the spread of antibiotic
Math Med & Biol 2005; 22: 187-208
resistance.” and “inappropriately
optimized cycles may hinder resistance
PNAS 2004 ; 101: 13285–13290
control”
42. Preventive Strategies
Active Surveillance Cultures + Contact Precautions
Identify both colonized & infected patients early
Restrict spread by strict infection control processes
43. ASC + Precautions
Best studied with MRSA; less with Gm Neg
ASC shows benefit in some; inconsistent
Mathematical modelling:
VRE: Culture (vs. none) K transmit ~40%
Culture + isolation K transmit 65%
MRSA: Routine cultures are ineffectual
ASC can reduce rates
Debated: When, how often,
Need RCT! Which patients (all vs. at risk)
Sites, Methods
44. The RCT; You asked for it!
Cluster randomized study
Compliance with 10 intervention ICUs (surveillance Cx + barrier)
barrier precautions 8 control ICUs (n= 5343 & 3705 respectively)
was suboptimal
Surveillance cultures on all (reported to Rx grp)
MRSA+VRE colonization & infection unchanged
N E J Med 2011; 364: 1407-18 40.4+3.3 vs 35.6+3.7 / 1000 patient days (p 0.35)
45. The VA Initiative
“MRSA Bundle” 2007 – 2010; 1.9 million admits ICU / non ICU
Universal nasal survl. 8.3 million patient days; “MRSA Bundle” initiated
Contact precautions Universal nasal surveill’nce:
Hand Hygiene Chromgenic agar/ PCR
“Infection control as
everyone’s + Contact precautions
responsibility” K ICU MRSA ~62% (relative risk)
N E J Med 2011; 364: 1419-30
K Non-ICU MRSA 45%
46. The Gist: STAR ICU vs. VA
While one can decry the deficiencies of
observational cohorts; RCTs often
underestimate benefits
The prime issue: methodology of surveillance
STAR: Routine Cx: Median positive ~ 5 days
VA: Chromgenic + PCR (“real time”)
Extrapolation to Spot-tests for gram negative MDROs limited
MDRO Gram Value of contact precautions is unsubstantiated
negatives
47. Decolonization:
I am not competent to discuss the
merits of Mupirocin to prevent MRSA
The problem of
“Dutch” Ideas
But am tempted to introduce the
Euthanasia
Legal drugs
concept of Selective Decontamination
Legal prostitution
of the Digestive Tract (SDD)……
“Going Dutch”
A function of living below
….interesting lessons!
sea level?
48. Methodology of SDD*
*Selective Decontamination of the Digestive Tract
1. Oral application of antibiotic:
Tobra+ Amphotercin+ Polymixin
(Vancomycin added if MRSA is J)
2. NG administration
3. Systemic Antibiotics for 24-48 hr
1 & 2: “Selective”; anaerobes preserved
Reduce GI/ Oropharynx colonization
CID 2006; 43: S70–4 3: Prevents early colonization / VAP
49. Outcomes with SDD
Rx Meta analysis
30 RCTs
5727 patients
Odds of VAP and death reduced;
Rx VAP; OR 0.35 (0.29-0.41)
Death; OR 0.8 (0.69-0.93)
Death K from 30% to 24%
D’amico NNT to prevent one death = 16
BMJ 1998; 316; 1275-85 Best effect in surgical ICU patients
50. So why not use SDD?
Rx
Resistance?
Fear of inducing bacterial resistance
Not conclusively established
Rx
Resistance?
Will it work when rate of bacterial
resistance is high in an ICU
AJRCCM 2001; 164: 382-88
AJRCCM 2001; 164: 338-9
Has been used to combat outbreaks of
AJRCCM 2002; 166: 1029-37 resistant organisms; not in endemic high-
Intens Care Med 1999; 25: 1323-6 resistance ICUs
51. SDD in India?
Rx
Mathematical Modeling*
Maximum effect shown when:
a. Colonization pr. with resistant bacteria is low
b. All patients at risk are given SDD
Rx c. No external source of potential pathogens
None of the above can be met in our ICUs
a. ESBL ~ 80%; MRSA ~50%; MDR
* Bootsma et al Pseudomonas~ 40%; MDR Acinetobacter
Intersci Conf Antimicrob Agents
Chemother. b. Not cost-effective to give SDD to everyone
2003 Sep 14-17; 43:
abstract no. K-698. c. Requires pre-emptive isolation (quarantine)
52. More Math Models!
The benefit of non-absorbable “antibiotic prophylaxis can only be
substantial if patient-to-patient transmission has already been
reduced to a subcritical level by barrier precautions”…..
“a firm theoretical argument against routine use of topical
antimicrobial prophylaxis”
53. Tackling MDROs!
We are facing the consequences of
decades of irresponsible use: So
control processes will be expensive
Best option: ASC + Contact Precautions
Real-time surveillance need development
ICU Antibiotic use needs to be reduced
Prophylactic Abx only work after
prevalence rates are reduced
Infection Control Processes remain
supreme
54. “Antibiotics are a non-
renewable resource”….
Laxminarayan & Brown 2001
…..use them wisely!