Gram Negative Bacteria


Article Author:
Junio Oliveira


Article Editor:
Wanda Reygaert


Editors In Chief:
Stephen Leslie
Karim Hamawy


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
3/9/2019 8:54:10 PM

Introduction

Gram-negative bacteria (GNB) are among the most significant public health problems in the world due to the high resistance to antibiotics. These microorganisms have great clinical importance in hospitals because they put patients in the intensive care unit (ICU) at high risk and lead to high morbidity and mortality.[1][2] Two large groups, Enterobacteriaceae and the non-fermenters, are responsible for most clinical isolates; nevertheless, other clinically concerning gram-negative organisms exist, including Neisseria, Haemophilus spp., Helicobacter pylori, and Chlamydia trachomatis

Antibiotic Resistance

These organisms have a range of mechanisms to prevent the action of many antimicrobials used in clinical medicine. Some of the mechanisms of resistance include efflux pumps,[3] alteration of the drug binding site and membrane permeability,[4] degradation enzymes, and the conformational change of the drug culminating in its inactivation.[5]

GNB have two membranes, an external and an internal. The external membrane expresses a potent immune response inducer, lipopolysaccharide (LPS), which it is composed of three units: a hydrophilic polysaccharide, O antigen, and a hydrophobic domain known as lipid A. Lipid A is responsible for the higher endotoxic activity of these bacteria.[6][7] However, the LPS is heterogeneous in the various bacterial groups, and some bacteria manifest this antigen weakly due to genetic changes and are not recognized by Toll-like receptors. In contrast, there are BGN groups that can trigger such a response in large proportions. Thus, LPS can trigger the innate immune response through Toll-like receptors 4 (TLR4), which occurs in many immune cells such as monocytes, macrophages, dendritic cells, and neutrophils. The resulting activation of the innate immune response mediated by LPS together with TLR4 receptors culminates in an exacerbated response with the production of cytokines, chemokines, and interferons and its suppression.

The response of the immune system depends on both the severity of the infectious process and the structure of the LPS in the aggressive bacteria, which imbricates to the virulence of the BGN and, as a consequence, while some bacteria like Escherichia coli potential induce the immune system, other bacteria like Helicobacter pylori are weakly antigenic.[8]

Enterobacteriaceae 

Enterobacteriaceae are a heterogeneous group widely dispersed in nature. They account for about 80% of gram-negative isolates with a myriad of disease-causing general/species in humans, including urinary tract infections, pneumonia, diarrhea, meningitis, sepsis, endotoxic shock, and many others. The general/species that frequently affect humans are EscherichiaProteusEnterobacterKlebsiella, CitrobacterYersinia, Shigella, and Salmonella among others. The laboratory characterization is an essential component when it comes to microorganisms; therefore, it is imperative to expose characteristics of Enterobacteriaceae, which are bacilli, non-sporulated, have variable motility, grow in the presence and absence of oxygen, ferment organisms of glucose, are cytochrome oxidase negative, and have the ability to reduce nitrate to nitrite.[9]

Antimicrobial Resistance

These organisms diffuse their plasmids by conjugation, which gives rise to resistance to almost all existing antibiotics. The family of enzymes carbapenemase – KPC, NDM-1, IMP, VIM, OXA-48 – is undoubtedly one of the most significant health challenges of the century, given the potential for dissemination between species and mortality rates due to infections caused by bacteria with such plasmids.[10] Colistin, one of the few antibiotics that still treat multiresistant infections, already has a mobile resistance gene, mcr-1, and Enterobacteriaceae has a crucial role in the spread of this gene, with worldwide reports.[11] Moreover, a further concern is that they usually associate these genes with other resistance genes (CTX-M, NDM, IMP), producing resistance to cephalosporins and carbapenems, enhancing the deleterious effects caused by these microorganisms.[6]

Non-Fermenters

The non-fermenter, gram-negative bacilli (BNF) have a lower frequency of isolation when compared to Enterobacteriaceae; however, they are a relevant group since they cause severe, fatal infections, especially in the hospital environment. They also cause opportunistic diseases in ICU patients who undergo invasive procedures. The main BNF microorganisms that cause disease in humans are Pseudomonas aeruginosa, Acinetobacter baumannii, Burkholderia cepacia, Stenotrophomonas., Alcaligenes, Moraxella. These stand out for being aerobic, non-sporulated, they are incapable of fermenting sugars, using them through the oxidative route.[12]

The critical issue regarding BNF, when it comes to the antimicrobial sensitivity profile, is undoubtedly their intrinsic resistance since they produce a variety of genes with multiple mechanisms capable of mitigating the microbicidal action. Thus, it stands out in P. aeruginosa, cephalosporinase of type AmpC, and efflux systems that confer resistance to b-lactams. The most frequent are MexAB-OprM[13]; and loss of OprD (which gives impermeability to the bacterial cell, due to the loss of porin)[14]. A. baumannii naturally produces AmpC cephalosporinase and also oxacillinase (OXA), leaving it spontaneously immune to many drugs. The genetic ingenuity of this microorganism goes further, and it combines high impermeability with genetic plasticity, combining with the resistance of mechanisms such as extended-spectrum b-lactamases (ESBL).[15] The Stenotrophomonas exhibit a pattern of intrinsic multi-resistance, especially in patients who have had contact with carbapenems. Thus, Stenotrophomonas present several efflux pumps and produces two carbapenemases – L1 (resistance to all carbapenems) and L2  (cephalosporinase),[16] in synthesis. These mechanisms, associated or separate, restrict the treatment options to an alarming level. Although it is sensitive to sulfamethoxazole-trimethoprim and has an increased resistance mediated by plasmids.[17]

Etiology

The gram-negative bacteria have a great ability to cause disease in humans and can reach almost all systems in the organism, such as digestive system, nervous system, urinary system, and the bloodstream, causing since diarrheal gastroenteritis until severe meningitis. Such microorganisms colonize the intestines, airways, and skin; which favors the spread to other parts of the human organism, especially in immunocompromised individuals. One of the greatest difficulties of health professionals is to treat nosocomial infections of the lower respiratory tract in which the pathogens GNB are involved, because although they are responsible for a good portion of these infections, they are non-responsive to antibiotic therapy due to the high resistance rates and the poor penetration of drugs into the lung parenchyma.[18] Another major concern is gastroenteritis caused by Enterobacteriaceae (Shigella spp., Salmonella spp., enteropathogenic E. coli), which affect millions of people around the world and are related to lack of sanitation.[19] Additionally, they are responsible for meningitis - a potentially fatal disease if not treated in time – it acquired both in the community and in the hospital environment.[20][21] The urinary tract infections are also common, especially in young women. However, these infections became a problem with the rampant emergence of multi-resistant bacteria. Finally, bacteremia is an important complication of these infections, also because of the above-mentioned resistance that the microorganisms demonstrated.[20]

Epidemiology

Considering the cosmopolitan character of gram-negative microorganisms and their ability to cause infections in humans, it is important to state the biggest problem that currently faces healthcare workers is bacterial groups that cause multiresistant infections. Multiresistant gram-negative infections (MDRs) are today one of the most significant health challenges in the world due to the inadequate response of these pathogens to antimicrobials, which have practically pulverized by the production of ESBL and carbapenemases. A little over twenty years ago appeared the first KPC carbapenemase reported in the United States, and since then, such infections spread globally. However, since the 1980s there have been reports of gram-negative strains of ESBL, especially in the hospital environment.[21] According to the Center for Disease Control and Prevention (CDC), in the United States, with the exception of Maine and Idaho, multiresistant gram-negative bacteria is rampant.[21] Still, in the US, Livorsi et al. found a variation in the incidence varying from 0.3 to 2.93 infections per 100000 person-years. Outside the United States, on almost every continent there are already reports of multiresistant bacteria. In Europe, for example, about 25000 people die each year from multidrug-resistant (MDR) infections.[22]

The extended-spectrum beta-lactamases (CTX-M, TEM, SHV, PER, VEB, TLA) are enzymes that hydrolyze extended-spectrum cephalosporins. From this family of enzymes, the most prevalent are CTX-M and its variations. Studies show that 12% of Ecoli isolates in the USA produce ESBL, while in Latin America and Asia this percentage may reach 27% and 38%, respectively. At the beginning of the ESBL outbreaks they had links to the hospital environment; however, today they are found in patients originating in the community.[23][24] Carbapenemases (KPC, NDM-1, IMP, VIM, OXA-48) characterically are enzymes that hydrolyze carbapenem and most other beta-lactams. In the United States, the most commonly detected are KPC, NDM, and OXA-48; in Europe, the most prevalent are OXA-48, KPC and VIM, being the NDM they are less incident. Further, an aggravation of these enzymes is their transfer by plasmids, which often carry additional genes of resistance, making these gram-negative bacteria pan-resistant.[23]

Finally, another vector of the global spread of these genes are the extensive capacity of interspecies transmission. Also, it is postulated that there is a risk of contracting a multidrug-resistant infection in patients with comorbidities, hospitalizations in ICUs, prior use of antibiotics and prolonged use of a central venous catheter.[21]

History and Physical

The findings of gram-negative infections are non-specific, not distinguishing them from other infectious diseases on physical examination. A classic example is pneumonia; its symptoms include fever, chest pain, dyspnea, and purulent expectoration; these symptoms may correlate with tachycardia, tachypnea, hypoxemia, and auscultatory signs of consolidation. However, these signs are not specific to the disease. Cultures are the only way to determine the organism.[25] Similarly, in bacterial meningitis, one may note fever, severe headache, nausea, vomiting, neck stiffness, prostration, and mental confusion. However, such features are not exclusive, and it requires other evidence to conclude the type of organism.[26]

Evaluation

Whereas the infections produced by gram-negative are practically indistinguishable from other etiologies, the laboratory characterization can define the organism and its antimicrobial susceptibility profile. Thus, the gold-standard examination of these infections are the cultures; however, they have the problem of a delay in the result. Another essential exam for bacterial isolates is the Gram stain, although simple, it can quickly distinguish the course of a drug intervention.  Enterobacteria, because of their heterogeneity, depend on various biochemical tests (Indol, Voges-Proskauer, catalase, cytochrome oxidase, urease, motility, citrate, ONPG, Dnase, decarboxylation of lysine, gas production among others), grown in primary isolation agar. Species such as E. coli, because they are fermenters of strong acids, they produce large quantities of mixed acids which make the pH of the media to present pink colonies. Others such as non-fermenters grow in primary isolation media (blood agar and MacConkey), in the OF-oxidation/fermentation medium - grow only in the aerobic environment.[9]

However, it is important to mention the identification of bacterial strains resistant to multiple drugs may require molecular methods, but they are not available in all laboratories. Phenotypic methods such as Modified Hodge (MHT) and Combined Diffusion Disc (CDT) using EDTA are a good alternative.[27] The MHT is a test based on the inactivation of carbapenems by bacterial strains containing the enzymes carbapenemases, enabling a susceptible strain to extend its growth to a disc containing the antimicrobial along the inoculum of the strain tested. This test is recommended for strains with high minimum inhibitory concentration (MIC) or reduced zones of inhibition in the disk.[28] The CDT comprises a test disc-diffusion with carbapenem antibiotics, where carbapenem discs are placed with and without EDTA, and their connection predicts whether the organism produces or does not carbapenemase.[29]

Treatment / Management

Treatment options for gram-negative MDR infections are limited, and the results are generally disappointing because of drug resistance. MDRs are still evolving, which provides resistance to novel antimicrobials. Thus, as the availability of new drugs progresses slowly, some previously abandoned options have reappeared, such as polymyxins and colistin that have high toxicity (nephrotoxicity and neurotoxicity). Furthermore, resistant genes to these drugs have been reported such as mcr-1 - cause additional concern. But it is known that the combination of these drugs with carbapenems may have an improved synergistic action.[30] Another drug of choice is tigecycline since it shows in vitro activity against MDR; however, there are limitations in its use as high doses are required, and tissue penetration is often poor, which impairs its action in vivo.[31]

Fosfomycin, an old drug used to treat urinary tract infections, has also resurfaced as a potential agent for the treatment of these MDR infections. However, monotherapy with this drug also results in resistance and its use is appropriate in conjunction with other agents such as carbapenems and polymyxin. This drug has moderate absorption, which restricts its use only for urinary tract infections.[32] Drugs once rejected because of their nephrotoxicity and ototoxicity, the aminoglycosides, have resurfaced again because of their effectiveness against gram-negative organisms. However, these drugs do not perform the same against MDRs except for urinary tract infections; they also exhibit less toxicity when compared to polymyxin and tigecycline and may be useful in combination therapy.[33]

The carbapenems are the last-choice drugs for ESBL-producing organisms; however, the appearance of carbapenemases has made treatment difficult. Monotherapy is rarely effective. However,  combination therapy with these drugs is effective and because of the high affinity of carbapenemases for ertapenem, making it a "bait" for the action of other carbapenems.

New drugs such as ceftazidime-avibactam and meropenem-varbobactam have emerged; the first is an antipseudomonal cephalosporin associated with a beta-lactamase inhibitor, while the second is a carbapenem with b-serine and has anti-lactamase activity. Early results are encouraging.[21]

Differential Diagnosis

  • Gram-positive bacterial infections (Staphylococcus spp., Streptococcus spp., Micrococcus spp.)
  • Viral infections (HIV, respiratory syncytial virus, influenzas)
  • Mycobacterium spp. and Nocardia spp.
  • Fungal infections (Cryptococcus spp, Aspergillus spp., Candida albicans)

Toxicity and Side Effect Management

Polymyxins have been in disuse since the 1970s because of their known toxicity, mainly because of their nephrotoxic effects. With the appearance of gram-negative MDR infections, they have revitalized. However, there are reports of problems with toxicity and increased resistance to these drugs.[34] The mechanism of renal toxicity exerted by these drugs occurs mainly through oxidative stress, resulting in mitochondrial dysfunction and loss of the membrane potential of this organelle. Apoptosis is also another effect attributed to this drug, which activates caspases 3, 8 and 9 of pulmonary epithelial cells.[35] The toxicity of polymyxins is related to concentration; however, the current pharmacokinetics and pharmacodynamics have already shown the dosage for this class of drugs is not the most appropriate, thus requiring new studies for correction, which could attenuate the toxicity of the drug.

Another class of drugs with toxic potential are the aminoglycosides which mainly cause ototoxicity and nephrotoxicity. These drugs block cationic channels of the ciliated cells in the inner ear. They have the same action with the mechanosensitive transduction channels of these cells, whereas inside these cells they promote biochemical changes that culminate in the elevation of intracellular calcium and the formation of reactive species of oxygen (EROS), which irreversibly damage the cell.[36] The nephrotoxicity of the aminoglycosides is mainly related to damage to the proximal tubule; the effects are relative to the dose and the time of exposure. The endocytosis of these drugs with consequent release of the lysosomes content is the mechanism by which the drugs exert their toxicity; also, they also block the calcium channels, culminating in the loss of this ion, magnesium, and potassium.[37]

Prognosis

Many variables are present in gram-negative infections; therefore, the prognosis of the diseases caused by these pathogens is difficult to measure and is not unanimous in the literature. However, such infections are usually associated with a poor outcome, mainly in elderly patients, with a history of comorbidities, those with solid organ transplantation and malignant diseases. Treatment success also depends on the causative microorganism and the site of infection. Serious infections with high mortality rates are related to delayed antibiotic therapy or inadequate therapy while appropriate antibiotic administration correlates with patient survival. Besides that, the lack of a well-defined protocol for these infections may lead to treatment failure, since suboptimal or inadequate administration contributes to poor results. Finally, monotherapy is also ineffective, especially when compared to combination therapy, which is related to good prognosis.[38]

Complications

Several complications may result from gram-negative infections, especially the enzyme producers that hydrolyze carbapenems. A concerning infection due to recurrence and ease of acquisition is the urinary tract, as it is increasingly common to find multidrug-resistant organisms in the community, and such infections, if not treated properly, could lead to renal failure, sepsis, and even death.[20] Similarly, the nosocomial infections in frail patients with suppressed immunity, comorbidities, and transient immunosuppressive status, make this combination a challenge for health professionals.[21]

In this sense, special care is necessary with patients who have suffered burns, because as there are more ports of entry for microorganisms; infections in burn patients can be potentially lethal and invasive depending on the microbial load and the pathogen itself.[39] Another risk is respiratory tract infections, mainly associated with mechanical ventilation, since gram-negatives are responsible for such infections, with Enterobacteriaceae and non-fermenters involved, with considerable potential for fatality.[40]

Deterrence and Patient Education

One of the chief difficulties in the treatment of multiresistant gram-negative infections is the excessive use of antibiotics, not only those acquired by the community but also in hospitals. As the MDRs became epidemic, it is observable that overuse of these antimicrobials was one of the causes that urgently requires addressing. Thus, measures aimed at changing the use of these drugs, with educational campaigns, as well as the fight against self-medication with practices such as monitoring of drug consumption and their registration in pharmacies are necessary to change the habit of the population and also health professionals.

Enhancing Healthcare Team Outcomes

The problem of multiresistant GNB infections is on the rise since the beginning of the 21st century. However, there is difficulty eradicating drug-resistant organisms because of the lack of effective antibiotics. Thus, simple measures such as regular hand hygiene, adequate sterilization of medical equipment, isolation of patients suspected or diagnosed with MDR microorganisms - especially those submitted to invasive procedures - with caution regarding the entry of external persons. All individuals should abide by infectious disease preventive rules established in the healthcare setting. Another significant action is the laboratory worker who isolates MDR pathogens to immediately inform the epidemiological surveillance the staff of the health establishment so that prevention and control measures are enacted promptly.

Results

In summary, the results at present are still not good, especially in elderly patients with a history of multiresistant BGN infection; however, the aforementioned measures, although simple, could save lives as well as avoid the spread of these MDR bacterial strains which pose a high risk to society for the reduced spectrum of drugs that address these infections, which, in addition to being often inefficient, also present high levels of toxicity.


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Gram Negative Bacteria - Questions

Take a quiz of the questions on this article.

Take Quiz
How do gram-negative bacteria appear after staining?

(Move Mouse on Image to Enlarge)
  • Image 5011 Not availableImage 5011 Not available
    Contributed by The Centers for Disease Control and Prevention (CDC)
Attributed To: Contributed by The Centers for Disease Control and Prevention (CDC)



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following antibiotics should not be used for treatment of Gram-negative infections?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following regions contains the greatest number of antigenic epitopes in gram-negative bacteria?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is not true regarding Gram negative organisms?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Gram-negative bacteria are one of the largest public health problems in the world due to a substantial decline in their sensitivity to antimicrobials. Which of the following options is false regarding gram-negative bacteria?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which gene is linked to polymyxin resistance?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Gram Negative Bacteria - References

References

Ak O,Batirel A,Ozer S,Çolakoğlu S, Nosocomial infections and risk factors in the intensive care unit of a teaching and research hospital: a prospective cohort study. Medical science monitor : international medical journal of experimental and clinical research. 2011 May     [PubMed]
Hormozi SF,Vasei N,Aminianfar M,Darvishi M,Saeedi AA, Antibiotic resistance in patients suffering from nosocomial infections in Besat Hospital. European journal of translational myology. 2018 Jul 10     [PubMed]
Li XZ,Plésiat P,Nikaido H, The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clinical microbiology reviews. 2015 Apr     [PubMed]
Ruppé É,Woerther PL,Barbier F, Mechanisms of antimicrobial resistance in Gram-negative bacilli. Annals of intensive care. 2015 Dec     [PubMed]
Naas T,Dortet L,Iorga BI, Structural and Functional Aspects of Class A Carbapenemases. Current drug targets. 2016     [PubMed]
Livermore DM, Current epidemiology and growing resistance of gram-negative pathogens. The Korean journal of internal medicine. 2012 Jun     [PubMed]
Auer GK,Weibel DB, Bacterial Cell Mechanics. Biochemistry. 2017 Jul 25     [PubMed]
Wang X,Quinn PJ, Endotoxins: lipopolysaccharides of gram-negative bacteria. Sub-cellular biochemistry. 2010     [PubMed]
Ng LS,Tan TY,Yeow SC, A cost-effective method for the presumptive identification of Enterobacteriaceae for diagnostic microbiology laboratories. Pathology. 2010 Apr     [PubMed]
Kim ES,Chong YP,Park SJ,Kim MN,Kim SH,Lee SO,Choi SH,Woo JH,Jeong JY,Kim YS, Detection and genetic features of MCR-1-producing plasmid in human Escherichia coli infection in South Korea. Diagnostic microbiology and infectious disease. 2017 Oct     [PubMed]
Pitout JD,Nordmann P,Poirel L, Carbapenemase-Producing Klebsiella pneumoniae, a Key Pathogen Set for Global Nosocomial Dominance. Antimicrobial agents and chemotherapy. 2015 Oct     [PubMed]
Hsu LY,Apisarnthanarak A,Khan E,Suwantarat N,Ghafur A,Tambyah PA, Carbapenem-Resistant Acinetobacter baumannii and Enterobacteriaceae in South and Southeast Asia. Clinical microbiology reviews. 2017 Jan     [PubMed]
Perry JD, A Decade of Development of Chromogenic Culture Media for Clinical Microbiology in an Era of Molecular Diagnostics. Clinical microbiology reviews. 2017 Apr     [PubMed]
Fruci M,Poole K, Aminoglycoside-inducible expression of the mexAB-oprM multidrug efflux operon in Pseudomonas aeruginosa: Involvement of the envelope stress-responsive AmgRS two-component system. PloS one. 2018     [PubMed]
Ocampo-Sosa AA,Cabot G,Rodríguez C,Roman E,Tubau F,Macia MD,Moya B,Zamorano L,Suárez C,Peña C,Domínguez MA,Moncalián G,Oliver A,Martínez-Martínez L, Alterations of OprD in carbapenem-intermediate and -susceptible strains of Pseudomonas aeruginosa isolated from patients with bacteremia in a Spanish multicenter study. Antimicrobial agents and chemotherapy. 2012 Apr     [PubMed]
Brooke JS, Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clinical microbiology reviews. 2012 Jan     [PubMed]
Yang Z,Liu W,Cui Q,Niu W,Li H,Zhao X,Wei X,Wang X,Huang S,Dong D,Lu S,Bai C,Li Y,Huang L,Yuan J, Prevalence and detection of Stenotrophomonas maltophilia carrying metallo-β-lactamase blaL1 in Beijing, China. Frontiers in microbiology. 2014     [PubMed]
Wenzler E,Fraidenburg DR,Scardina T,Danziger LH, Inhaled Antibiotics for Gram-Negative Respiratory Infections. Clinical microbiology reviews. 2016 Jul     [PubMed]
Crump JA,Heyderman RS, A Perspective on Invasive Salmonella Disease in Africa. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2015 Nov 1     [PubMed]
Lee YC,Hsiao CY,Hung MC,Hung SC,Wang HP,Huang YJ,Wang JT, Bacteremic Urinary Tract Infection Caused by Multidrug-Resistant Enterobacteriaceae Are Associated With Severe Sepsis at Admission: Implication for Empirical Therapy. Medicine. 2016 May     [PubMed]
Porreca AM,Sullivan KV,Gallagher JC, The Epidemiology, Evolution, and Treatment of KPC-Producing Organisms. Current infectious disease reports. 2018 May 5     [PubMed]
Livorsi DJ,Chorazy ML,Schweizer ML,Balkenende EC,Blevins AE,Nair R,Samore MH,Nelson RE,Khader K,Perencevich EN, A systematic review of the epidemiology of carbapenem-resistant Enterobacteriaceae in the United States. Antimicrobial resistance and infection control. 2018     [PubMed]
Weingarten RA,Johnson RC,Conlan S,Ramsburg AM,Dekker JP,Lau AF,Khil P,Odom RT,Deming C,Park M,Thomas PJ,Henderson DK,Palmore TN,Segre JA,Frank KM, Genomic Analysis of Hospital Plumbing Reveals Diverse Reservoir of Bacterial Plasmids Conferring Carbapenem Resistance. mBio. 2018 Feb 6     [PubMed]
Mabie M,Wunderink RG, Use and limitations of clinical and radiologic diagnosis of pneumonia. Seminars in respiratory infections. 2003 Jun     [PubMed]
Ala A,Rahmani F,Abdollahi S,Parsian Z, Accuracy of Neck stiffness, Kernig, Brudzinski, and Jolt Accentuation of Headache Signs in Early Detection of Meningitis. Emergency (Tehran, Iran). 2018     [PubMed]
Aseem R,Shenoy S,Mala SS,Baliga S,Ashish A, Approach to Carbapenemase Detection in {i}Klebsiella pneumoniae{/i} in Routine Diagnostic Laboratories. Journal of clinical and diagnostic research : JCDR. 2016 Dec     [PubMed]
Anwar M,Ejaz H,Zafar A,Hamid H, Phenotypic Detection of Metallo-Beta-Lactamases in Carbapenem Resistant Acinetobacter baumannii Isolated from Pediatric Patients in Pakistan. Journal of pathogens. 2016     [PubMed]
Pasteran F,Gonzalez LJ,Albornoz E,Bahr G,Vila AJ,Corso A, Triton Hodge Test: Improved Protocol for Modified Hodge Test for Enhanced Detection of NDM and Other Carbapenemase Producers. Journal of clinical microbiology. 2016 Mar     [PubMed]
Rodrigo-Troyano A,Sibila O, The respiratory threat posed by multidrug resistant Gram-negative bacteria. Respirology (Carlton, Vic.). 2017 Oct     [PubMed]
Pirii LE,Friedrich AW,Rossen JWA,Vogels W,Beerthuizen GIJM,Nieuwenhuis MK,Kooistra-Smid AMD,Bathoorn E, Extensive colonization with carbapenemase-producing microorganisms in Romanian burn patients: infectious consequences from the Colectiv fire disaster. European journal of clinical microbiology     [PubMed]
Hawkey PM, Multidrug-resistant Gram-negative bacteria: a product of globalization. The Journal of hospital infection. 2015 Apr     [PubMed]
Bader MS,Loeb M,Brooks AA, An update on the management of urinary tract infections in the era of antimicrobial resistance. Postgraduate medicine. 2017 Mar     [PubMed]
Wargo KA,Edwards JD, Aminoglycoside-induced nephrotoxicity. Journal of pharmacy practice. 2014 Dec     [PubMed]
Zakuan ZD,Suresh K, Rational use of intravenous polymyxin B and colistin: A review. The Medical journal of Malaysia. 2018 Oct     [PubMed]
Meagher AK,Ambrose PG,Grasela TH,Ellis-Grosse EJ, Pharmacokinetic/pharmacodynamic profile for tigecycline-a new glycylcycline antimicrobial agent. Diagnostic microbiology and infectious disease. 2005 Jul     [PubMed]
Ahmed MU,Velkov T,Lin YW,Yun B,Nowell CJ,Zhou F,Zhou QT,Chan K,Azad MAK,Li J, Potential Toxicity of Polymyxins in Human Lung Epithelial Cells. Antimicrobial agents and chemotherapy. 2017 Jun     [PubMed]
Vattimo Mde F,Watanabe M,da Fonseca CD,Neiva LB,Pessoa EA,Borges FT, Polymyxin B Nephrotoxicity: From Organ to Cell Damage. PloS one. 2016     [PubMed]
Li H,Steyger PS, Synergistic ototoxicity due to noise exposure and aminoglycoside antibiotics. Noise     [PubMed]
Ward DT,McLarnon SJ,Riccardi D, Aminoglycosides increase intracellular calcium levels and ERK activity in proximal tubular OK cells expressing the extracellular calcium-sensing receptor. Journal of the American Society of Nephrology : JASN. 2002 Jun     [PubMed]
Paño Pardo JR,Serrano Villar S,Ramos Ramos JC,Pintado V, Infections caused by carbapenemase-producing Enterobacteriaceae: risk factors, clinical features and prognosis. Enfermedades infecciosas y microbiologia clinica. 2014 Dec;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Surgery-Urologic. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Surgery-Urologic, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Surgery-Urologic, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Surgery-Urologic. When it is time for the Surgery-Urologic board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Surgery-Urologic.