Enterobacter Aerogenes - Essay Example

ENTEROBACTER AEROGENES Introduction: The modern challenge that most of the medical practitioners all over the world face today is, not so much, the identification of new microorganisms and the diseases caused by them, as the difficulty experienced in treating some of the already very familiar diseases which have suddenly become very stubborn to treatment with commonly used antibiotics and chemotherapeutic agents. This is mainly due to the phenomenon of drug-resistance which some of the microorganisms manage to develop ingeniously to protect themselves and their progeny from destruction by modern drugs. So a real war of wits has been going on between these little pathogens and the mighty medical science. In the meantime it becomes imperative for physicians and surgeons to be vary of selecting the right antibiotic to combat these rogue organisms which play tantrums with them, at times, to the detriment of the patients. One of the most notorious groups of organisms is the Gram -ve bacteria, the most prominent among them being the Enterobacteriaceae. 2. Natural habitat of Enterobacter Aerogenes (pronounced as " en-ter-o-BAC-ter air-AH-jen-eez ") Hierarchical classifications of Enterobacter aerogenes :The following list attempts to classify Enterobacter aerogenes into different subsets : Hierarchy: Bacteria Gram-Negative Bacteria Gram-Negative Facultatively Anaerobic Rods Enterobacteriaceae Enterobacter Enterobacter aerogenes. Enterobacter is a gram-negative bacillus that belongs to the Enterobacteriaceae family. Other members of this family include Klebsiella, Escherichia, Citrobacter, Serratia, Salmonella, and Shigella species, among many others. Enterobacteriaceae are the most common bacterial isolates recovered from clinical specimens. Enterobacter aerogenes is a species found in water, soil, sewage, dairy products, and the faeces of man and other animals. Organisms previously identified as motile strains of Aerobacter aerogenes are now placed in this species. They also have a synonym as Klebsiella mobilis. As part of the Enterobacteriaceae family, Enterobacter aerogenes is related to E. coli and salmonella. In terms of size, E. aerogenes is smaller than many of its microbial cousins, but its occurrence in hospitals and resistance to antibiotics have made it of particular importance. As E. aerogenes continues to evolve new strains, it will continue to pose challenges to the biomedical community. As a facultative anaerobe, it thrives in environments with little or no oxygen, such as soil, sewage and feces. Enterobacter aerogenes is a Gram negative rod-shaped bacterium in the same family as Esherichia coli. It can grow on many of the same selective media as Esherichia coli, including: MacConkey Agar, EMB agar and Lauryl-Tryptose broth. E. aerogenes ferments lactose, producing acid and gas like Esherichia coli and is classified as an example of coliform bacteria. E. aerogenes grows better at temperatures between 34 - 40 degrees C. E. aerogenes carries out 2,3-butanediol fermentation and thus give a positive test in the Voges-Proskauer test while E. coli is negative. E.coli is positive for the indole test while E. aerogenes is negative, this is a very reliable test. 5 E. aerogenes can grow on Simmon's citrate agar while E. coli does not. There are a lot of similarities between Enterobacter aerogenes and Klebsiella pneumonia. The urease test is one of the few tests that distinguishes E. aerogenes from K. pneumonia. . Klebsiella is positive for urease production while Enterobacter is negative. In the microbiology laboratory, colonies of Enterobacteriaceae appear large, dull-gray, and dry or mucoid on sheep blood agar. All Enterobacteriaceae ferment glucose and, consequently, are able to grow in aerobic and anaerobic atmospheres. MacConkey agar is a lactose-containing medium that is selective for nonfastidious gram-negative bacilli such as Enterobacteriaceae. Using the enzymes beta-galactosidase and beta-galactoside permeases, the most frequently encountered species of Enterobacter strains activate the pH indicator (neutral red) included in MacConkey agar, giving a red stain to the growing colonies. Klebsiella and Enterobacter species may appear similar as mucoid colonies but can be differentiated with a few specific tests. In contrast to Klebsiella species, Enterobacter organisms are motile, usually ornithine decarboxylase-positive, and urease-negative. Many different species comprise the genus Enterobacter. Some have never been associated with human infections. The most commonly isolated species include E cloacae and E aerogenes, followed by E sakazakii (recently reclassified into the Cronobacter genus), which produces a characteristic yellow pigment The source of infection may be endogenous (via colonization of the skin, gastrointestinal tract, or urinary tract) or exogenous, resulting from the ubiquitous nature of Enterobacter species. Multiple reports have incriminated the hands of personnel, endoscopes, blood products, devices for monitoring intra-arterial pressure, and stethoscopes as sources of infection. Outbreaks have been traced to various common sources: total parenteral nutrition solutions, isotonic saline solutions, albumin, digital thermometers, and dialysis equipment. Enterobacter species have a global presence in both adult and neonatal ICUs. Surveillance data and outbreak case reports from North and South America, Europe, and Asia indicate that these bacteria represent an important opportunistic pathogen among neonates and debilitated patients in ICUs. Enterobacter species are major pathogens in early post-lung transplant pneumonia. In most cases, the bacteria are transmitted from the donor. Enterobacter aerogenes are Gram-negative rods. They are motile, which refers to their ability to move spontaneously and actively, consuming energy in the process. They do not produce endospores. They are facultative, meaning that they make Adenosine-5'-triphosphate - ATP - by aerobic respiration if oxygen is present but are also capable of switching to fermentation. That means these organisms can thrive both in aerobic and anerobic environments. These infections can be contracted endogenously via colonization of the skin, gastrointestinal tract, or urinary tract or exogenously from the "ubiquitous nature of these bacteria" (Sinave). In many cases, the hands of personnel, intravenous solutions, endoscopes, blood products, devices for monitoring intra-arterial pressure, and stethoscopes have been deemed the source for the infection. (Sinave) 3. Pathogenic Capabilities of Enterobacter Aerogenes : Enterobacter infections cause considerable mortality and morbidity rates. Enterobacter species can cause disease in virtually any body compartment. They are responsible for frequent and severe nosocomial infections that require prolonged hospitalization, multiple and varied imaging studies and laboratory tests, various surgical and nonsurgical procedures, and powerful and expensive antimicrobial agents. Nosocomial infections pertain to or originate in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance, the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. Most importantly, Enterobacter infections that do not directly cause death can cause considerable suffering in many patients, most of whom are already afflicted with chronic diseases. In patients with Enterobacter bacteremia, the most important factor in determining the risk of mortality is the severity of the underlying disease. Higher 30-day mortality rates were noted in patients presenting with septic shock and increasing Acute Physiology and Chronic Health Evaluation II scores. Other factors which aid in the outcome of Enterobacter bacteremia include thrombocytopenia, hemorrhage, a concurrent pulmonary focus of infection, renal insufficiency, admission in an ICU, prolonged hospitalization, prior surgery, intravascular and/or urinary catheters, immunosuppressive therapy, neutropenia, antibiotic resistance, and inappropriate antimicrobial therapy. Recent studies have demonstrated that empirical aminoglycoside use and appropriate initial antibiotic therapy were associated with lower mortality rates, whereas vasopressor use, ICU care, and acute renal failure were associated with higher mortality rates. Independent risk factors for mortality included cephalosporin resistance, trimethoprim-sulfamethoxazole resistance, mechanical ventilation, and nosocomial infection. (Deal EN, et al. 2007 & Ye Y, et al. 2006 )7,8 Crude mortality rates associated with Enterobacter infections range from 15-87%, but most reported rates range from 20-46%. Attributable mortality rates are reported to range from 6-40%. Bacteremia with cephalosporin-resistant Enterobacter species is associated with a 30-day mortality rate that significantly exceeds that of infections with susceptible strains (33.7% vs 18.6%). Mortality rates associated with Enterobacter pneumonia are higher than those of pneumonia due to many other gram-negative bacilli. These rates range from 14-71%. As with bacteremia, the severity of the underlying disease is the major factor that predicts outcome. Other factors that indicate an unfavorable outcome include the extent of the disease as seen on chest radiographs, corticosteroid therapy, isolation of multiple pathogens from lower respiratory tract secretions, and, possibly, treatment with a single antibiotic. A review of 17 cases of Enterobacter endocarditis reported an overall mortality rate of 44.4%. ABIILITY TO INVADE HOST: Enterobacter infections are most common in neonates and in elderly individuals, reflecting the increased prevalence of severe underlying diseases at these age extremes. In the pediatric ICU setting, an age younger than 2.5 years is a risk factor for colonization. Although community-acquired Enterobacter infections are occasionally reported, nosocomial Enterobacter infections are, by far, most common. Patients most susceptible to Enterobacter infections are those who stay in the hospital, especially the ICU, for prolonged periods. Other major risk factors of Enterobacter infection include prior use of antimicrobial agents, concomitant malignancy (especially hemopoietic and solid-organ malignancies), hepatobiliary disease, ulcers of the upper gastrointestinal tract, use of foreign devices such as intravenous catheters, and serious underlying conditions such as burns, mechanical ventilation, and immunosuppression. National surveillance programs continually demonstrate that Enterobacter species remain a significant source of morbidity and mortality in hospitalized patients in the United States. In the Surveillance and Control of Pathogens of Epidemiological Importance [SCOPE] project, 24,179 nosocomial bloodstream infections from 1995-2002 were analyzed. Enterobacter species were the second-most-common gram-negative organism behind Pseudomonas aeruginosa; however, both bacteria were reported to each represent 4.7% of bloodstream infections in ICU settings. Enterobacter species represent 3.1% of bloodstream infections in non-ICU wards. Of nearly 75,000 gram-negative organisms collected from ICU patients in the United States between 1993 and 2004, Enterobacter species comprised 13.5% of the isolates.( Lockart, et al.2008)1 The National Healthcare Safety Network (NHSN) reported on healthcare-associated infections (HAI) between 2006 and 2007. They found Enterobacter species to be the eighth most common cause of HAI (5% of all infections) and the fourth most common gram-negative cause of HAIs.( Hidron, Al. et al. 2008)2 Previous reports from the National Nosocomial Infections Surveillance System (NNIS) demonstrated that Enterobacter species caused 11.2% of pneumonia cases in all types of ICUs, ranking third after Staphylococcus aureus (18.1%) and P aeruginosa (17%). The corresponding rates among patients in pediatric ICUs were 9.8% for pneumonia, 6.8% for bloodstream infections, and 9.5% for UTIs.( NNIS System Reports)3,4,5 Enterobacter species were also among the most frequent pathogens involved in surgical-site infections, as reported in the NNIS report from October 1986 to April 1997. The isolation rate was 9.5% (with enterococci, coagulase-negative staphylococci, S aureus, and P aeruginosa rates being 15.3%, 12.6%, 11.2%, and 10.3%, respectively). 4. Virulence Factors : These bacteria have an outer membrane that contains, among other things, lipopolysaccharides from which lipid-A plays a major role in sepsis. Lipid-A, also known as endotoxin, is the major stimulus for the release of cytokines, which are the mediators of systemic inflammation and its complications. Enterobacter aerogenes develops increased multidrug resistance via a functional alteration of outer-membrane permeability associated with a decrease in porin function. They are an opportunistic pathogens that rarely cause disease in otherwise healthy individuals. This bacterium's virulence seems to be due largely to an endotoxin that it produces. Nosocomial infections are the most frequent type of Enterobacter infections, but community-acquired infections are sometimes observed. The bacteria usually infects people who stay in the hospital, especially on the ICU, for long periods of time as well as people how have used many antimicrobial agents, have serious underlying conditions (eg: diabetes, malignancies, burns, mechanical ventilation, etc.), use foreign devices such as intravenous catheters, and immunosuppression. 5. Symptoms Produced by Enterobacter Aerogenes : Bacteremia Most cases of Enterobacter bacteremia are nosocomial, frequently acquired in the ICU. E cloacae, followed by E aerogenes, are by far the species implicated most frequently in Enterobacter bacteremia cases. Symptoms of Enterobacter bacteremia are similar to those of bacteremia due to other gram-negative bacilli. More than 80% of children and adults with Enterobacter bacteremia develop fever. Hypotension and shock occur in as many as one third of cases. Disseminated intravascular coagulation, jaundice, acute respiratory distress syndrome, and other organ failures reflect the severity of septic shock. Purpura fulminans and hemorrhagic bullae usually observed with meningococci or viruses causing hemorrhagic fever may be part of the clinical presentation of Enterobacter bacteremia. Cyanosis and mottling is frequently reported in children with Enterobacter bacteremia. Lower respiratory tract infections The clinical presentations caused by Enterobacter lower respiratory tract infections include asymptomatic colonization, tracheobronchitis, pneumonia, lung abscess, and empyema. Symptoms of Enterobacter pneumonia are not specific to these bacteria. Fever, cough, production of purulent sputum, tachypnea, and tachycardia are usually present. As with infections caused by organisms such as Streptococcus pneumoniae, many Enterobacter infections in elderly debilitated patients do not cause a systemic inflammatory reaction. However, this clinical presentation is by no means benign, and the associated mortality rate is particularly high in this population. Skin and soft-tissue infections In most cases, Enterobacter skin and soft-tissue infections are hospital-acquired and include cellulitis, fasciitis, myositis, abscesses, and wound infections. Enterobacter species can infect surgical wounds in any body site, and these infections are clinically indistinguishable from infections caused by other bacteria Urinary tract infections : Enterobacter UTI is indistinguishable from a UTI caused by other gram-negative bacilli. Pyelonephritis with or without bacteremia, prostatitis, cystitis, and asymptomatic bacteriuria can be caused by Enterobacter species, as with Escherichia coli and other gram-negative bacilli. Most Enterobacter UTIs are nosocomial and are associated with indwelling urinary catheters and/or prior antibiotic therapy. Intra-abdominal infections : Enterobacter species may be isolated together with colonic flora in intra-abdominal abscesses or peritonitis following intestinal perforation or surgery. A frequent cause of Enterobacter involvement is prior digestive-tract colonization by Enterobacter species during hospitalization. Case reports have described Enterobacter hepatobiliary sepsis, including emphysematous cholecystitis, suppurative cholangitis, and hepatic gas gangrene in a child after liver transplantation. Hemorrhagic necrotizing pancreatitis developed in a 72-year-old woman with obstructive jaundice. Ophthalmic infections Enterobacter species account for a small fraction of postsurgical endophthalmitis cases. Most ophthalmic infections are caused by gram-positive organisms, but Enterobacter species and Pseudomonas species are among the most aggressive pathogens. Bone and joint infections Enterobacter species are occasionally implicated in septic arthritis, on both native and prosthetic joints, and can result in osteomyelitis and discitis in adults and children. Lower respiratory tract infections Enterobacter lower respiratory tract infections can manifest identically to those caused by S pneumoniae or other organisms. The physical examination findings may include apprehension, high fever or hypothermia, tachycardia, hypoxemia, tachypnea, and cyanosis. Patients with pulmonary consolidation may present with crackling sounds, dullness to percussion, tubular breath sounds, and egophony. Pleural effusion may manifest as dullness to percussion and decreased breath sounds. ( 6. Treatment of diseases caused by Enterobacter Aerogenes : Data on antibiotic resistance are available from the Intensive Care Antimicrobial Resistance Epidemiology (ICARE) surveillance report. The rates of Enterobacter resistance to third-generation cephalosporins were 25.3% in ICUs, 22.3% among non-ICU inpatients, 10.1% among ambulatory patients, and as high as 36.2% in pediatric ICUs.( NNIS System Report )6 These "ICU bugs" cause significant morbidity and mortality, and infection management is complicated by resistance to multiple antibiotics. Enterobacter species possess inducible beta-lactamases, which are undetectable in vitro but are responsible for resistance during treatment. Physicians treating patients with Enterobacter infections are advised to avoid certain antibiotics, particularly third-generation cephalosporins, because resistant mutants can quickly appear. The crucial first step is appropriate identification of the bacteria. Antibiograms must be interpreted with respect to the different resistance mechanisms and their respective frequency, as is reported for Enterobacter species, even if routine in vitro antibiotic susceptibility testing has not identified resistance. Enterobacter species contain a subpopulation of organisms that produce a beta-lactamase at low-levels. Once exposed to broad-spectrum cephalosporins, the subpopulation of beta-lactamase-producing organisms predominate. Thus, an Enterobacter infection that appears sensitive to cephalosporins at diagnosis may quickly develop into a resistant infection during therapy. Carbapenems and cefepime have a more stable beta-lactam ring against the lactamase produced by resistant strains of Enterobacter. In this investigation, 45E.aerogenes isolates originating from 33hospitalized patients were available. E. aerogenes isolates were grouped into 11different antibiotypes depending upon their susceptibilities to 14different antimicrobial drugs. Almost all strains were resistant to ampicillin, cefazolin, and cefuroxime but were sensitive to gentamicin, temocillin, amikacin, and imipenem. The antimicrobial resistance patterns were pooled, and it was found that 91to 100% of the strains were resistant to ampicillin, cefazolin, and cefuroxime; 82to 84% were resistant to co-trimoxazole, aztreonam, ceftazidime, and ciprofloxacin; 56% were resistant to ceftriaxone, 40% were resistant to piperacillin-tazobactam; 31% were resistant to amoxicillin-clavulanate; and 2% were resistant to temocillin. (Sheikh Jalaluddin, et al. 1998 )10 Treament E. aerogenes is resistant to most antibiotics, including chloramphenicol, quinolones and tetracycline. As a result, the use of "old" drugs---that is, drugs that were commonly prescribed in past decades---is growing in popularity. Another popular treatment is using a combination of drugs such as imipenem and gentamicin. TYGACIL( tigecycline IV ) of Wyeth has been found to be effective against E. aerogenes in in vitro tests. However, the safety and efficacy of TYGACIL in patients with hospital-acquired pneumonia have not been established. (www.wyeth.com) * * * * * * * * * * * * * * * * * * Reference : References 1. Lockhart SR, Abramson MA, Beekmann SE, et al. Antimicrobial resistance among Gram-negative bacilli causing infections in intensive care unit patients in the United States between 1993 and 2004. J Clin Microbiol. Oct 2007;45(10):3352-9. [Medline]. 2. Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA. NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007. Infect Control Hosp Epidemiol. Nov 2008;29(11):996-1011. [Medline]. 3. National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) report, data summary from October 1986-April 1997, issued May 1997. A report from the NNIS System. Am J Infect Control. Dec 1997;25(6):477-87. [Medline]. 4. National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1990-May 1999, issued June 1999. Am J Infect Control. Dec 1999;27(6):520-32. [Medline]. 5. National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control. Dec 2004;32(8):470-85. [Medline]. 6. National Nosocomial Infections Surveillance System. Intensive Care Antimicrobial Resistance Epidemiology (ICARE) Surveillance Report, data summary from January 1996 through December 1997: A report from the National Nosocomial Infections Surveillance (NNIS) System. Am J Infect Control. Jun 1999;27(3):279-84. [Medline]. 7. Deal EN, Micek ST, Ritchie DJ, et al. Predictors of in-hospital mortality for bloodstream infections caused by Enterobacter species or Citrobacter freundii. Pharmacotherapy. Feb 2007;27(2):191-9. [Medline]. 8. Ye Y, Li JB, Ye DQ, et al. Enterobacter bacteremia: Clinical features, risk factors for multiresistance and mortality in a Chinese University Hospital. Infection. Oct 2006;34(5):252-7. [Medline]. 9. Author: Susan L Fraser, MD, Infectious Diseases Service, Walter Reed Army Medical Center; Chairman, Infection Control Committee; Associate Professor of Medicine, Uniformed Services University of the Health Sciences Coauthor(s): Michael Arnett, MD, Resident, Department of Medicine, Tripler Army Medical Center; Christian P Sinave, MD, Associate Professor, Department of Medical Microbiology and Infectious Diseases, University of Sherbrooke, Canada. Medscape MedscapeCME eMedicine Drug Reference MEDLINE Enterobacter Infections 10. Sheikh Jalaluddin,1,2 Jeanne-Marie Devaster,1 Robert Scheen,1 Michele Gerard,3 and Jean-Paul Butzler1,2,* Journal of Clinical Microbiology, July 1998, p. 1846-1852, Vol. 36, No. 7 0095-1137/98/$04.00+0 Copyright 1998, American Society for Microbiology. http://jcm.asm.org/cgi/content/full/36/7/1846#T1 * * * * * * * * * * * * * * * * * * Read More