Kilbourne ED. Influenza pandemics of the 20th century. Emerg Infect Dis. 2006 Jan. 121:9-14

do not provide the additional protection provided by TMP-SMX against other infections and some are not as effective at low CD4 T-cell counts. Early initiation of HAART is favourable in individuals with PCP. The improvement in systemic and local immunity following continous use of HAART translate into very low risk of PCP if profilaxis is discontinued in population with CD4 T cell count 200 cellsµL for more than 3 months. Tuberculosis Tuberculosis TB infection in HIV patient remains a major global public health challenges, with estimated 1.4 million patients world wide. By the end of 2009, an estimated 2.6 million individuals had become newly infected with HIV and 1.8 million had died of AIDS in that year alone. TB is the most common opportunistic infection among HIV infected individuals, and co-infected individuals are at high risk of death. Lawn S. et al. 2009 TB may occur in any stage of HIV disease and is frequently the first recognized presentation of underlying HIV infection. As compared to people without HIV, people living with HIV PLWH have 20-fold higher risk of developing TB and the risk continues to increase as CD4 cell counts progressively decline. Although ART can reduced the incidence of TB both at the individual and population level, PLWH on ART still have higher TB incidence rates and a higher risk of dying from TB. This may be due to delayed initiation of ART or the fact that patients present with advance TB or both. Routine TB screening among PLWH offers the opportunity to identify those without TB, prevent TB by chemoprophylaxis as well as to diagnose and promptly treat TB. However co- administration of ART along with anti-TB therapy present several management challenges, including drug-drug interactions, overlapping drug toxicities and immune reconstitution syndrome. Lawn S et al. 2009 Presentation Clinical symptoms of TB pulmonary disease are similar to those caused by other mycobacteria : fever, night sweats, weight loss, productive cough, dyspnea, central chest pain and sometimes hemoptysis. Diagnosis Diagnosis of active TB disease in HIV- infected persons is difficult, because patients with HIV-associated TB have fewer bacilli in their sputum than do HIV-uninfected patients with pulmonary TB. In addition it has been observed that presence of a cough for 3 weeks is not sensitive enough on its own as a symptom of TB in HIV-infected persons. Because diagnosis in most regions depends on microscopic examination of Ziehl-Neelsen- stained sputum smears, which has low sensitivity among HIV-infected persons, most HIV- infected persons are not tested with the standard diagnostic methodology. The specific impact of methods that optimize the use of smear microscopy is not well understood for HIV-infected persons. Mycobacterial culture is the gold standard for TB diagnosis and is routinely recommended to assist the diagnosis of TB in HIV-infected persons, although it is frustratingly slow. HIV infection compromises the validity and effectiveness of chest radiography in the diagnosis of pulmonary TB in HIV-infected persons, and the findings could be normal for up to 14 of HIV- infected persons who have culture confirmed pulmonary TB. However, chest radiography remains an important adjunct in the diagnosis of TB, and its use must be expanded, including the use of advance and innovative technology such as digital imaging. Padmapriyadarsini C et al. 2011 The WHO recommends TB screening at the time that HIV infection is diagnosed, before the initiation of antiretroviral therapy and at regular interval during follow up. It was recommended that screening for TB should include asking questions about the present of any one of current cough, fever, night sweats or weight loss. In the hospital setting, bacteriological examination mostly failed to find Mycobacterium TB from sputum smear, and this is not simply just by difficulty to get the specimen. Because of the poor performance of sputum smear microscopy in HIV-infected patients, recently the WHO endorsed the used of GeneXpert-Rif for the rapid diagnosis of TB as well as rifampicin resistance among HIV-infected individuals with clinical suspicion of TB. WHO report. 2010; Padmapriyadarsini Cet al 2011 Chest X ray do not show typical feature of lung TB especially in patient with low CD 4 cell count. The spectrum of radiographic manifestation of Pulmonary TB is dependent on the relative level of immunodeficiency. During the early phase of HIV when individuals are not immunosupressed the radiographic pattern is similar to HIV un-infected individuals with more typical lesions-upper lobe infiltrates with or without cavities. With advancing immune- suppression, extra pulmonary involvement, intrathoraxic mediastinal lymphadenopathy, lower lobe infiltrates and milliary TB become more common. Padmapriyadarsini C et al. 2011 Treatment The basic principles of treatment for HIV-associated TB are the same as for HIV uninfected individuals. TB treatment category in the same for TB and HIV-TB co infection, but the antiretroviral therapy ARV the guideline recommend to avoid Nevirapine in the regimen and use Efavirenz instead, because there is interaction between nevirapine and rifampicin. The WHO currently recommended that management of HIV-TB co infection by routine TB screening among PLWH offers the opportunity to identify those without TB, prevent TB by chemoprophylaxis as well as to diagnose and to treat TB as soon as the diagnostic can be made, and to start of ARV as soon as the patient response to anti TB drugs is stable, do not waiting too long. We can wait until 8 weeks or earlier, depend on the patient‟s condition. According to the guideline, TB treatment completed in six months, but experience have showed that many HIV-TB co infection may reappear with TB symptoms and sign in one or two months after completing in six moths anti TB drugs treatment. WHO report. 2010; Padmapriyadarsini C et al. 2011 Bacterial Pneumonia HIV related bacterial infection of the lower respiratory tract is common and occurs at levels of immunosupression. Risk factors for HIV- related bacterial pneumonia are declining CD4 lymphocyte count, cigarette smoking and injecting drug use. Incidence of bacterial pneumonia is five times greater in HIV positive population than in otherwise similar but HIV-negative population; the incidence of pneumococcal disease, including pneumonia, is 10 times greater and the development of pneumococcal septicemia is 100 times greater. Beck. 2005 Recurrent pneumonia two or more episodes in a 12-month period is classified as AIDS- defining. The etiology of community-acquired pneumonia CAP among HIV-seropositive individuals is similar to that of the general population with Streptococcus pneumonia and Haemophilus influenza predominating. Staphylococcus aureus has been reported at a greater frequency than in the general population. Pseudomonas aeroginosa has been noted more commonly at low CD4 T-cell counts. Although atypical pathogens such as Legionella pneumophila, Mycoplasma pneumonia and Chlamydophila Chlamidia pneumonia have not been frequently reported in HIV-related bacterial pneumonia, this may reflect diagnostic difficulties, and there are data to support that these occur at the same frequency in HIV-seropositive and HIV-seronegative populations. As with immunocompetent individuals . Gram-negative pathogens should be considered especially likely in those who develop pneumonia when hospitalized. Dunleavy A. et al. 2009; Dockrell DH et al. 2011 Presentation Presenting symptoms are similar to HIV-seronegative individuals and typically have an acute onset hours to days.The classical physical signs are those of lung consolidation, although there is an increased tendency to rapid progression: cavitation, parapnemonic effusion and empyema formation The peripheral white blood count WBC is usually elevated but may be low in more severe cases. Diagnosis Etiologic diagnosis of bacterial infection in HIV-positive or AIDS patients is based on clinical presentation, supporting radiographic findings, sputum smears and cultures. Where a purulent sputum sample can be obtained prior to the first dose of antibiotics, this should be sent for Gram stain and culture to guide therapy. Broncho-Alveolar Lavage BAL has been effective to establish diagnosis with sensitivities above 80 when samples were obtained before the initiation of antibiotic therapy. When pneumonia is suspected a chest radiograph should be obtained. Radiological features are similar to HIV- seronegative individuals. Patchy, lobar or segmental consolidation appears on plain radiograph, although an increased frequency of interstitial infiltrates has been recently reported; cavitation within consolidation, when the infection is cause by gram-negative organisms, as for example pseudomonas and multiple cavitating nodules in case of septic embolism especially in IVDU. Blood cultures should be routinely performed in these patients because of the high incidence of bacteremia. Dunleavy A. et al. 2009; Dockrell DH et al. 2011 Treatment While empirical therapy usually directed against bacterial pathogens may be appropriate for patients with CD4 counts 200 cellsµL, every effort should be made to confirm a specific diagnosis in the more immunocompromised individual. Initial anti-microbial treatment is usually empirical and should be chosen according to; a pneumonia severity; bthe likelyhood of particular pathogens as indicated by risk factors; c the potential for antibiotic resistant and d potential toxicities. A number of guidelines developed to guide the management of CAP in HIV-seronegative individuals exist and the possible regimens suggested in these guidelines are adapted from them. HIV-seropositive individuals with community-acquired pneumonia should be treated as per HIV-seronegative populations. Antibiotic prophylaxis is not indicated for bacterial pneumonia. The capsular polysaccharide vaccine protects against pneumococcal serotypes. The Departement of Health includes HIV-seropositive individuals amongs t the “high- risk” groups for whom vaccination is recommended. References Beck J. Immunocompromised Host. Proc Am Thorax Soc 2005;2:423-7 Benson CA et al. Treating Opportunistic Infections Among HIV Infected Adults and Adolescents Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association InfectiousDiseases Society of America. Available at: http: www.cdc.govhivtopicstreatmentindex.htm Dockrell DH, Breen R, Lipman M, Miller RF. Pulmonary Opportunistic infections. 2011. HIV Medicine. 12 suppl.2 25-42. Dunleavy A, Lipman M, Miller R. Infection in the HIV compromised host. In: maskell N, Millar A, eds. Oxford Desk Reference Respiratory Medicine. Oxford, Oxford University Press. 2009: 210-217 Lawn S. Churchyard G. Epidemiology of HIV associated tuberculosis. Curr Opin HIV AIDS 2009;4:325-33 Padmapriyadarsini C, Narendran G, Swaminathan S. Diagnosis Treatment of Tuberculosis in HIV co-invected patients. 2011. Indian J Med Res 134;850-865 Tuberkulosis, Pedoman Diagnosis dan Penatalaksanaan di Indonesia. 2011. Perhimpunan Dokter Paru Indonesia. WHO report 2010. Global tuberculosis control. Available from: http:whqlibdoc.who.intpublications20109789241564069_eng.pdf,accessed on September 20,2011. Methicillin Resistant Staphylococcus Aureus MRSA and Extended Spectrum Beta- Lactamases ESBL Anak Agung Ayu Yuli Gayatri, Tuti Parwati Merati Division of Tropical and Infectious Disease Department of Internal Medicine Udayana University School of Medicine-Sanglah Hospital Denpasar Introduction Resistance of pathogenic organisms to countenance antibiotics has become a world wide problem with serious consequences on the treatment of infectious diseases. The heightened use or misuse of antibiotics in human medicine, agriculture and veterinary is primarily contributing to the phenomenon. There is an alarming increase of antibiotic resistance in bacteria that cause either community infections or hospital acquired infections. Resistance genes borne on chromosomal, and increasingly, on transmissible extrachromosomal elements. The resulting resistant clones e.g. Meticillin-resistant Staphylococcus aureus MRSA USA 300, Escherichia coli ST 131 and Klebsiella ST258 are disseminated rapidly worldwide. This spread is fascilitated by interspecies gene transmission, poor sanitation and hygiene in communities and hospitals and the increasing frequency of global, travel, trade and disease transmission. Alekshun et al. 2007 The true prevalence of MRSA and ESBLs infections is not known and is probably underestimated because of difficulties encounters in their detection. In the USA, data reported to the Centers for Disease Control and Prevention CDC National Nosocomial Infection Surveillance System and the National Healthcare Safety Network reflect an increase over the past decade in rates of infections caused by some Multi Drug Resistant -Gram Negative Bacteria MDR-GNB, defined as resistance to one or more tested antimicrobial s in three or more antimicrobial classes. Among Gram- negative organisms associated with central line-associated infections, catheter-associated urinary tract infections, ventilator- associated pneumonia and surgical site infections that were reported during 2009-20010 aproximately 15 of K pneumoaie or Klebsiella oxitoca, 2 of E coli and 65 of A baumannii isolate. In Asia, data of E coli resistance varied from 5 in Korea to 23.3 in Indonesia. In 2010-2012, Sanglah hospital Denpasar Bali reported 32 affected MRSA infection patients, with SSTI was the most common clinical presentation followed by sepsis, osteomyelitis, UTI and pneumonia. All cases were more likely to be resistant to ß-lactams but remain sensitive to vancomycin, linezolide and many non ß- lactam antibiotics including clindamycin, erythromycin and trimethroprim- sulfamethoxazole. Sievert et al. 2013; Gayatri Y. 2013 Treatment of these multiple drug resistant organisms, pose unique challenges to clinicians, clinical microbiologists, infection control professionals and antibacterial- discovery scienties. It is generally recognized that patients infected with MRSA and ESBL- producing organisms are at risk for poor outcome if they are treated with anti bacterials to which the organisms exhibits high level resistance. The mortality rate in these susceptibility mismatched patients has ranged from 42-100. Chong Yet al. 2011

1. Methicillin- Resistant Staphylococcus Aureus MRSA

MRSA was first described in 1961, almost immediately after the agent was introduced into clinical practice. MRSA are a type of staphylococcus bacteria that are resistant to many antibiotics. MRSA bacteria are more likely to develop when antibiotics are used too often or are not used correctly. Staphylococcus bacteria only become a problem when they cause infection. For some people especially those who are weak or ill, these infections can become serious. MRSA in an opportunistic bacterium which may colonize and grow readily on the skin and mucous membranes of a person without harm to that person. It competes with other microorganisms found on the skin surface and is commonly found in the nose, groin, perineum or any other warm, moist sites. The human skin is constantly shedding skin scales-MRSA is shed with the skin as it falls from the human body. The greater the number of MRSA colonies on a person, the greater the potential for contamination of the environment and the transmission of MRSA to others. Infected and colonized patients are the reservoir of MRSA both in hospital and the community with transmission generally being via contact with health workers. Effective, rapid laboratory diagnosis and susceptibility testing is critical in treating, managing any preventing MRSA infections.

1.1. MRSA Infections in Hospital

MRSA that is acquired in a hospital or healthcare setting is called healthcare-associated methicillin-resistant Staphylococcus aureus HA-MRSA. In most cases, a person who is already sick or who has a weakened immune system becomes infected with HA-MRSA. These infections can occur in wounds or skin, burns, and IV or other sites where tubes enter the body, as well as in the eyes, bones, heart or blood. Some patients harbor MRSA on their skin or nose without harm „colonised‟. However these patient may develop infections if the MRSA spread to other parts of the body e.g. if MRSA spread from colonized nose to a wound. When this happens the resulting infection is described as „endogenous‟. Some patients are at increased risk of developing infection. They include those with breaks in their skin due to wounds or indwelling catheters which allow MRSA to enter the body, and those with certain types of deficiency in their immune system. This includes patients who: i. Are in hospital and long-term care fascilities for a long time, ii. Are on hemodialysis, iii. Receive cancer treatment or medicines that weaken their immune system, iv. Inject illegal drugs, v. Had surgery in the past year. The prevention of horizontal transmission of MRSA has become increasingly important as the prevalence of this pathogen increases. Oral carriage of MRSA may serve as a reservoir for re-colonization of other body sites or for cross-infection to other patients or health care workers. Therefore, it is important that consideration be given to the oral cavity if eradication of colonization by MRSA is clinically appropriate. Eradication of throat carriage of MRSA has been achieve with use of topical chlorhexidine 0.2 in addition to normal control measures of patient isolation, nasal mupirocin and chlorhexidine body washes.

1.2. MRSA infection in the Community

MRSA infections can also occur in healthy people who have not recently been in the hospital. The strains were labeled community-associated MRSA CA-MRSA if they had been isolated within 48 hours of hospitalization from patients who had not been in any hospital for 1 year. CA- MRSA resistance is usually limited to β-lactams and the strains remain susceptible to clindamycin, gentamycin, sulfamethoxazole-trimethoprim, vancimycin, rifampin, tetracycline and linezolide. Most CA-MRSA strains characterized by carry the Panton-Valentine leukocidin genes, leading to leukocyte destruction, skin abcesses and necrotizing pneumonitis, and also presence of staphylococcal chromosome cassette mec SCCmec IVa, a novel smaller variant of the methicillin-resistant locus. Other S aureus strains that are not resistant to methicillin will be referred to as methicillin- sensitive Staphylococcus aureus MSSA. Most of CA-MRSA infections are on the skin or less commonly lung infections. These infections can occur among people who are likely to have cuts or wounds and who have close contact with one another, such as members of sports teams. People who may be at risk are: i. Atlletes and other people who may share items such as towels or razors, ii. Children in day-care. iii. Members of military, iv. People who have gotten tattoos. In some cases these organisms can cause invasive infection such as septic arthritis, bacteriemia, or community-acquired necrotising pneumonia. An early skin infection often has the initial appearance of an insect bite. These infections often develop into cellulitis, furuncles, large boils or clusters of boils up to 10 cm in diameter and deep-seated abscesses often in the thighs or buttocks. If the bacteria gain access to the lungs, fortunately a rare event, a devastating pneumonia that kills more than 40 of patients can result. The fundamental differences between HA-MRSA and CA-MRSA have been discussed and summarized in table1. Table 1. Comparison between healthcare-associated and community-acquired Methicillin resistant Staphylococcus aureus. Sievert et al. 2013 CA-MRSA HA-MRSA Clinical spectrum Skin and soft tissue infections Wound infections, urinary tarct infections and bacteraemia Epidemiology Affected healthy people in the community Mostly affects hospital patients Underlying condition Dernmatological Healthcare associated risk factors Age group Younger older Resistant pattern Sensitive to multiple antibiotics Resistant to multiple antibiotic Toxin production May produce PVL toxin Not yet reported produce PVL toxin

1.3. MRSA testing

MRSA screening may be undertaken for the following reasons: 1. Screening requirement determined from the multidrug Resistant Organism MDRO Risk Assesment 2. If found positive after admission from a clinical sample 3. As part of Outbreak Management MRSA specimens A purple bacterial swab is use to sample the following sites: 1. Nasal swab one swab for both nostrils 2. Groin swab one swab for both sides 3. Perineum swab 4. Wound swab-including decubitus ulcer pressure sore or surgical wound and device insertion e.g. IV tracheostomy, drain, suprapubic 5. Additional site:  Umbilicus in neonates  Catheter urine specimen if patient for screening has an indwelling urinary catheter  Sputum from patient with recent MRSA respiratory tract infection not nasal colonization

1.4. Care of patient with MRSA:

 Placement of patients in single room  Treatment procedure applies to all patients and staff who may or may not be currently receiving systemic antibiotic treatment for MRSA infection  Contact Precautions with own toilet facilities if Ensuite not available, allocate own commode chair in room or dedicated toilet  Hand hygiene with antimicrobial liquid soap or alcohol- based hand rub  Dedicated patient-care equipment or disinfect between use if shared with other patients e.g. blood pressure and oximetry equipment  Remove unnecessary equipment from the isolation room and ensure supplies are not overstocked within the room  If no Ensuite shower is available the patient showers last in the communal shower and the shower is disinfected after use  Mupirocin Bactroban is to be applied to the anterior nasal nares three times a day  Tridosan 1 is to be used for daily washing of skin and bathing. Cetrimide shampoo for hair washing twice weekly  Treatment is to be for an initial period of seven days  Visitors do not wear PPE but are encourage to perform hand hygiene after visiting the patient  Where possible, permanent staff should be used Treatment Patients who are severely ill or have a rapidly progressing infection should be referred to the hospital for consideration of intravenous antibiotics. Intravenous vancomycin is the most commonly used antibiotic for this indication. Vancomycin can have serious side effects, especially in elderly persons. These side effects could include ototoxicity loss of hearing or other auditory damage, nephrotoxicity damage to the kidneys or renal system, and allergic reactions such as fever and rash. Infusion of vancomycin, especially when to rapid, can result in flushing, hypotension, and tachycardia known as the “red man syndrome”. Vancomycin given by mouth is not absorbed and is not effective against MRSAEmergence of vancomycin-intermediate and vancomycin-resistant MRSA VISA and VRSA, respectively has been reported, but are uncommon Moran. 2006. Linezolid may offer an alternative to intravenous vancomycin. Recent studies have shown that the adverse event rate of linezolid is not significantly different than that for vancomycin and that linezolid is an effective agent for SSTIs including those caused by MRSA. Daptomycin has been used effectively in cases of complicated SSTI and for treatment of CA-MRSA bacteremia. Quinupristindalfopristin is active against MRSA, but is rarely used due to an adverse-effect profile and potential cross-resistance with clindamycin-resistant strains. Tigecycline is active against MRSA and it has FDA approval for the treatment of skin and soft tissue infections Rybak. 2005; Moran.2006. Patients with localized infection and without systemic toxicity may be managed as outpatients with oral medications. Oral antibiotic therapy should be continued until there is resolution of signs of acute inflammation; this typically occurs within 7-14 days. Options for oral antibiotics include trimethoprim-sulfamethoxazole, clindamycin, linezolid or tetracyclines eg, minocycline or doxycycline .Moran, 2006; Rybak, 2005. Access to oral linezolid may be limited due to formulary restrictions and other cost related issues. Some infectious disease specialists save linezolid for use in infections due to organisms resistant to other agents. This conservative approach is supported by reports of the emergence of linezolid-resistant organisms in healthcare settings Kelly, 2006. Topical, rather than oral, antibiotics can be used to treat superficial lesions. For instance, topical mupirocin TID for ~7 days has been utilized for treatment of limited impetigo Stevens, 2005; Swartz 2005. Of note, resistance to mupirocin may develop, but this usually occurs in the setting of prolonged usage. For multiple or larger CA-MRSA lesions, oral antibiotics are recommended. These drugs generally have activity against CA-MRSA: 1. Vancomycin Vancocyn® 15 mgkg IV q12 hours 2. Daptomycin Cubicin® 4 mgkg IV daily higher dosages are used for bacteremiaendocarditis Intravenous or Oral Antibiotics 3. Linezolid Zyvox® 600 mg IV or PO twice daily 4. Clindamycin Cleocin® 900 mg IV q8 hours or 300 –450 mg PO QID 5. Oral Antibiotics • Tetracyclines • Doxycycline Vibramycin® 100 mg PO twice daily • Minocycline Minocin® 100 mg PO twice daily • Trimethoprim-sulfamethoxazole Bactrim®, Septra® 1 double-strength with 160 TMP800 SMX tablet twice daily 6. Rifampin Rifadin® 300 mg PO twice daily 7. Topical Antibiotics • Topical mupirocin Bactroban® apply to each nares twice daily • Chlorhexidine body soaps, shower with soap daily used for decolonization purposes, not treatment Dosages listed assume normal kidney and liver function; for patients with abnormal values, drug dosage adjustments may be needed. Some antibiotics listed are not recommended in children or during pregnancy.

1.5. MRSA Treatment in the Setting of Highly Active Antiretroviral Therapy HAART

Although several oral agents are available, co-infection with HIV and the use of antiretroviral therapy may limit treatment options in some patients. TMP-SMX use may be limited in HIV patients due to pre-existing drug allergy. Clindamycin may be associated with Clostridium difficile colitis, a potentially vexing issue among HIV-patients. Linezolid use may be limited by thrombocytopenia necessitating weekly monitoring of complete blood counts. Linezolid may also interact with psychotropic medications such as monoamine oxidase inhibitors MAOIs and selective serotonin reuptake inhibitors SSRIs. Ideally patients should be titrated off of SSRIs prior to taking linezolid, but in many clinical situations this may not be possible. In those situations, patients should be warned to watch for and report any signs or symptoms suggestive of the serotonin syndrome which include hyperthermia, agitation, tremors, myoclonus, altered mental status, andor diaphoresis Rybak, 2006. Drug-drug interactions limit the co-administration of rifampin with several antiretroviral agents including protease inhibitors and non-nucleoside reverse transcriptase inhibitors. Rifampin is a powerful inducer of the cytochrome P450 enzyme system, leading to a decrease in antiretroviral plasma levels below the inhibitory concentration of 50 IC 50 of the latter and potentially leading to viral rebound. Rifampin should be avoided in patients receiving protease inhibitors and an alternate antibiotic, such as clindamycin, linezolid or tetracycline should be selected.

2. Extende Spectrum β-Lactamase ESBL

There is no consensus of the precise definition of ESBLs. β-lactamases are bacterial enzymes that ineffective β-lactam antibiotics by hydrolysis, which results in ineffective compounds. One group of β-lactamases, extended-spectrum β-lactamases ESBLs have the ability to hydrolyse and cause resistance to various types of the newer β-lactam antibiotics, including the expanded-spectrum or third generation cephalosporins eg, cefotaxime, ceftriaxone, ceftazidime and monobactams eg, aztreonam, but not the cephamycins eg, cefoxitin and cefotetan and carbapenem eg, imipenem, meropenem and ertapenem. ESBL has generally been defined as transmissible β- lactamases that can be inhibited by clavulanic acid, tazobactam or sulbactam, and or which are encoded by genes that can be exchanged between bacteria. Most ESBLs can be devided into three groups: TEM, SVH and CTX-M types. The currently most common genetic variant of ESBL is CTX-M. Paterson DL et al. 2005

2.1. Mechanisms of Transmission

A review of the literature on mechanism of transmission of MDR-GNB was problematic for three main reasons; the low number of studies; the low availability of high quality studies and the high heterogeneity of definitions, settings and pathogens. Patient-to patient transmission was frequently thought to be the most important route of transmission whenever several patients shared clonally related isolates. This is based on the hypothesis that colonized or infected patients are the only reservoir for the microorganism. However, intermediate vectors for spread between patients, including contaminated hands of healthcare workers HCWs, environment, and visitors should also be taken into consideration for the prevention and control of healthcare-associated MDR-GNB transmission.

2.2. Extended Spectrum β- lactamase Escherichia coli ESBL E-coli

ESBL producing E coli are antibiotic resistant strains. In most respect they are no different from other strains of E coli in that can harbored as part of the normal flora and can cause urinary tract infections, bacteraemia and meningitis in susceptible individuals. A key