Please confirm that you would like to log out of Medscape.
If you log out, you will be required to enter your username and password the next time you visit.
Log outCancel
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017
| Contributor Information
Swipe to advance
Images from Endo A, Shiraishi A, Aiboshi J, Hayashi Y, Otomo Y. J Intensive Care. 2014;2(1):13. [Open access.] PMID: 25520829, PMCID: PMC4267704.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
These images depict a patient with septic shock and purpura fulminans caused by β-lactamase-negative ampicillin-resistant Hemophilus influenzae. Images A and B: Day 1 of hospitalization. Image C: Hospital day 9, in which gangrene of the bilateral limbs, the facial region, and penis progressed gradually. All the limbs were complicated with infection and eventually amputated. The patient succumbed to sepsis on hospital day 34.
Emerging and spreading antimicrobial resistance is a serious global health threat.[1,2] In the United States alone, more than 2 million people every year acquire serious infections with bacteria that are resistant to one or more antibiotics.[1] At least 23,000 affected individuals die as a direct consequence of antibiotic-resistant infections, and many more suffer complications.[1] These infections also have a large impact on healthcare costs, as patients treated for antibiotic-resistant infections often[1,2]:
Receive prolonged courses of antibiotic therapy
Require the use of more costly antibiotics
Have longer hospital stays
Require more frequent medical follow-up
For example, each occurrence of a bloodstream infection (bacteremia) caused by extended-spectrum β-lactamase-producing (ESBL) Enterobacteriaceae (ESBLs) adds over $40,000 in US hospital costs.[1]
The most important factor contributing to resistant organisms is the use and overuse/misuse of antibiotics.[1,2]
Images from Polilli E, Ursini T, Mazzotta E, et al. Ann Clin Microbiol Antimicrob. 2012;11:6. [Open access.] PMID: 22404900, PMCID: PMC3324387.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
The photo and radiograph depict right-heel osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) in a renal transplant recipient with Fabry-Anderson disease. First-line therapy with intravenous (IV) teicoplanin and second-line IV tigecycline were ineffective, but treatment with third-line IV daptomycin monotherapy at 4 mg/kg/qd for 4 weeks was successful.
Risk Factors for Infections with MRDOs
Multidrug-resistant organisms (MDROs), also known as "superbugs," are microorganisms, predominantly bacteria, that are resistant to one or more classes of antimicrobial agents.[3,4] Although the names of certain MDROs describe resistance to only one agent (eg, MRSA, vancomycin-resistant Enterococcus [VRE]), these pathogens are frequently resistant to most available antimicrobials.[4]
Factors that raise the risk for infection with MDROs include the following:
Recent receipt of antimicrobials[1]
Immunosuppressed state (eg, on chemotherapy, have a malignancy, undergoing/received organ and/or bone marrow transplantation) and chronic diseases and inflammatory conditions (eg, diabetes, renal disease)[1]
Older age and lower functional status[5]
Undergoing hemodialysis, surgery, and/or other invasive procedures[1,5]
Presence of indwelling devices (eg, central venous catheter, urinary catheters, endotracheal tubes)[5]
Hospitalization or living in a long-term care facility[1,5]
Image from the CDC.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
MDRO Alerts
In 2013, the Centers for Disease Control and Prevention (CDC) for the first time released a report that prioritized bacterial antibiotic-resistance threats in the United States, as outlined below.[1]
Urgent threats
Clostridium difficile
Carbapenem-resistant Enterobacteriaceae (CRE) (Enterobacteriaceae include Klebsiella pneumonia and Escherichia coli, as well as species [spp] of Enterobacter, Serratia, Proteus, Providencia, and Morganella[6])
Drug-resistant Neisseria gonorrhoeae
Serious threats
Multidrug-resistant Acinetobacter and Pseudomonas aeruginosa
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
In February 2017, the World Health Organization (WHO) released their first global priority list of antibiotic-resistant pathogens in an effort "to guide and promote research and development (R&D) of new antibiotics."[6,7]Mycobacteria were excluded owing to the fact that they are a recognized global health threat already urgently targeted by existing, dedicated programs.[6,7]
Priority 1: Critical
Carbapenem-resistant Acinetobacter baumannii and P aeruginosa
MRSA, vancomycin-intermediate S aureus (VISA), and VRSA
Clarithromycin-resistant Helicobacter pylori
Fluoroquinolone-resistant Campylobacter spp and Salmonella spp
Third-generation cephalosporin-resistant, fluoroquinolone-resistant N gonorrhoeae
Priority 3: Medium
Penicillin-nonsusceptible S pneumoniae
Ampicillin-resistant H influenzae
Fluoroquinolone-resistant Shigella spp
In June 2017, the WHO released their 20th Model List of Essential Medicines, which included new advice on antibiotic use, categorized on the basis of their resistance potential.[8,9] Agents that should be widely available for common infections are key "Access" antibiotics; those that should be used for specific, limited indications are in the "Watch" group; and antibiotics that should be saved for the most serious conditions as "last-resort" options are in the "Reserve" group.[8,9]
Image courtesy of Sharanjeet Thind, MD.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
This is the foot of a patient who developed a polymicrobial infection, including carbapenem-resistant Acinetobacter. Surgery and IV antibiotic therapy were required.
The following slides discuss the nine WHO critical- and high-priority pathogens as well as Candida auris, a fungus that is emerging as a serious threat in worldwide healthcare facilities.[10]
WHO Priority 1: Critical
Carbapenem-resistant Acinetobacter baumannii
A baumannii is a gram-negative bacterium that naturally exists in soil and water and has a propensity to form biofilm.[11] This opportunistic pathogen can colonize the skin, wounds, and the respiratory tract, as well as ventilator equipment.[11] Thus, it is a common cause of nosocomial pneumonia, especially in patients on mechanical ventilation, and bacteremia in critically ill patients.[1]
A baumannii can contaminate the environment and has been associated with outbreaks in hospitals. Annually, about 12,000 US healthcare-associated Acinetobacter infections occur, of which 7,300 are multidrug resistant (MDR) and cause 500 deaths.[1] A large majority of the MDR isolates are resistant to carbapenems.
Images from (1) Pignatti M, Gerunda GE, Rompianesi G, et al. Patient Saf Surg. 2013;7(1):28. [Open access.] PMID: 24139428, PMCID: PMC3847491 (left inset); and (2) the CDC (background).
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
Left (inset): Dehiscent abdominal wound colonized by A baumannii after liver retransplantation (due to hepatitis B infection). Right (background): Three-dimensional (3D) computer-generated image of a group of MDR Acinetobacter spp arranged in a sheetlike configuration, rendered based on scanning electron microscopic (SEM) imagery.
A baumannii is inherently resistant to several classes of antibiotics.[1,12,13] Agents that may have activity against the organism depending on susceptibility testing include certain aminoglycosides and anti-pseudomonal cephalosporins, carbapenems, and quinolones.[13] Sulbactam is a beta-lactamase inhibitor that also has activity against A. baumanii; in the United States, it is available in combination with ampicillin.[12-14]
In the setting of carbapenem resistance, therapeutic options include minocycline, tigecycline, and polymxins, all of which should be used in combination with a carbapenem, namely imipenem, meropenem, or doripenem.[12-14]
Image from Flickr/John Campbell.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
A diabetic plantar ulcer is shown. Patients with diabetes are at risk for P aeruginosa infection.
Carbapenem-resistant Pseudomonas aeruginosa
P aeruginosa is another common cause of US healthcare-associated infections (HAIs) including pneumonia and bacteremia, as well as surgical site, wound, and urinary tract infections (UTIs).[15] This gram-negative pathogen causes an estimated 51,000 HAIs and has become increasingly resistant to several antibiotic classes, including aminoglycosides, penicillins, cephalosporins, and carbapenems.
Approximately 6,700 (13%) of severe P aeruginosa HAIs are MDR infections, leading to about 440 deaths each year.[1] Surveillance studies reveal that carbapenem resistance among clinical isolates ranges from 11.4% to 21.9%, varying greatly across different states.[16]
Image from the CDC/Janice Haney Carr.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
This is a colorized SEM image of several P aeruginosa bacteria.
Some strains of carbapenem-resistant Pseudomonas may retain susceptibility to other classes of antibiotics such as anti-pseudomonal fluoroquinolones (ciprofloxacin, levofloxacin), aminoglycosides, piperacillin/tazobactam, cefepime, and ceftazidime.[16]
If suspicion for drug resistance exists, perform susceptibility testing to polymixins and the newer generation cephalosporins ceftolozane/tazobactam and ceftazidime/avibactam. A combination of multiple antibiotics may be required to treat severe P aeruginosa infections, especially when managing them empirically.[16]
Image courtesy of Medscape.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
Computed tomography (CT) scan of Escherichia coli right pyelonephritis.
ESBL is an enzyme produced by gram-negative bacteria that hydrolyzes penicillins, aztreonam, and third-generation cephalosporins, thereby conferring resistance to these antibiotics.[17] The main producers of ESBL are E coli, Klebsiella pneumonia, and Klebsiella oxytoca, but many other Enterobacteriaceae also produce this enzyme.
Similar to non-drug-resistant Enterobacteriaceae, the ESBL-producing strains (ESBLs) are a common cause of UTIs, community-acquired pneumonia (CAP), and healthcare-associated pneumonia (HCAP), as well as surgical site, wound, and intra-abdominal infections—but the ESBLs are associated with poorer outcomes.[18,19] Approximately 1,700 US deaths each year are attributable to ESBLs; mortality increases up to 57% when these organisms cause bacteremia, as compared to non-ESBL-producing Enterobacteriaceae.[1] Overall, annually, about 26,000 (19%) of 140,000 Enterobacteriaceae HAIs in the United States result from ESBLs, and these rates are on the rise.[1]
Adapted images from Espinar MJ, Miranda IM, Costa-de-Oliveira S, Rocha R, Rodrigues AG, Pina-Vaz C. PLoS One. 2015;10(8):e0134737. [Open access.] PMID: 26237422, PMCID: PMC4523193.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
These are representative examples of random amplified polymorphic DNA (RAPD) patterns of (1) six strains of ESBL-positive E coli in three patients (left panel) and (2) six strains of ESBL-positive K pneumoniae in another set of three patients (right panel). All the patients had undergone kidney transplantation and suffered recurrent UTIs; two sets of isolates were recovered from each patient (first UTI and a subsequent UTI). M-DNA ladder 100 bp (Fermentas).
Detection of ESBLs is based on evidence of resistance to third-generation cephalosporins as well as blocked resistance in the presence of a beta-lactamase inhibitor such as clavulanate. Automated systems can reliably detect ESBLs.[18] Screening tests such as disk diffusion or microdilution should be confirmed by more specific methods, such as minimum inhibitory concentration (MIC) broth dilution or E-test reagent strips. Real-time polymerase chain reaction (PCR) for a specific gene-conferring resistance can also be used, if available.[18]
Adapted image from the CDC/Alissa Eckert and Jennifer Oosthuizen.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
This is a 3D computer-generated image of a group of ESBL Enterobacteriaceae (E coli).
The treatment of choice for ESBL infections is carbapenems.[17,20] If the organism is susceptible, agents such as quinolones, sulfamethoxazole/trimethoprim (SMX/TMP), aminoglycosides, and cefepime (if low MIC) can be used. Fosfomycin has been effective for ESBL-associated UTIs.[17,21]
As a last resort, and if the pathogen is susceptible, newer agents such as second-generation cephalosporin/β-lactamase inhibitor combinations ceftolozane/tazobactam or ceftazidime/avibactam should be used.[20,22] Piperacillin/tazobactam is not recommended as it appears to be inferior to carbapenem therapy for ESBL bacteremia.[20,22]
Adapted image from the CDC.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
CDC National Heathcare Safety Network (NHSN) antibiotic-resistance map for carbapenem-resistant Enterobacteriaceae spp. CAUTIs = catheter-associated UTIs, CLABIs = central line-associated bloodstream infections, and SSIs = surgical site infections.
Carbapenemases and carbapenem-resistant Enterobacteriaceae
Carbapenemases are enzymes that can hydrolyze and inhibit almost all β-lactam antibiotics, including carbapenems.[23-25] Other mechanisms can lead to carbapenem resistance, such as the expression of a cephalosporinase or an ESBL, in combination with bacterial porin loss.[23-25] Genes coding for resistance may be present on mobile elements, with the potential to spread.[23,24]
Images from (1) the CDC (adapted) (top) and (2) Yang Q, Fang L, Fu Y, Du X Shen Y, Yu Y. PLoS One. 2015;10(6):e0129454. [Open access.] PMID: 26047502, PMCID: PMC4457825 (bottom).
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
The top image depicts the pulsed-field gel electrophoresis (PFGE) technique. The bottom image shows a PFGE analysis of New Delhi metallo-β-lactamase (NDM)-1-producing K pneumoniae.
The first discovered and most commonly occurring carbapenemase is K pneumonia carbapenemase (KPC).[26] Several other types of carbapenemases have been identified in the United States, including NDM, which is resistant to a larger number of antibiotics than other types of CRE.[27,28] Consider this type of CRE in patients who have travelled from India or Pakistan.[24,26]
E coli, Citrobacter, Salmonella, and Shigella, among other Enterobacteriaceae, can also become CREs. These organisms can cause HAIs such CLABSIs, CAUTIs, and SSIs.[15,26] Other gram-negative bacteria, including Acinetobacter and Pseudomonas, can become resistant to carbapenems too.[15]
Images from (1) Flickr/John Campbell (left) and (2) Pignatti M, Gerunda GE, Rompianesi G, et al. Patient Saf Surg. 2013;7(1):28. [Open access.] PMID: 24139428, PMCID: PMC3847491 (right).
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
Left: Urine collection container and bag. Indwelling urinary catheters are a risk factor for the development of CRE. Right: Dehiscent abdominal wound colonized by E faecium after liver transplantation.
Carbapenem-resistant Enterobacteriaceae
CRE infections are invasive and associated with a high mortality.[24] Of the estimated 140,000 Enterobacteriaceae HAIs in the United States each year, about 9,300 are attributable to CRE.[1] Two CRE bacteria alone cause about 610 deaths annually: CRE Klebsiella spp and CRE E coli spp.[1]
Automated testing can identify CREs by evidence of elevated carbapenem MICs above their acceptable breakpoints. Confirmation can be obtained with phenotypic tests (modified Hodge test [MHT], mass spectrometric detection) or genotypic tests (PCR assays, DNA microarrays) that can concurrently screen for several different types of enzymes.[24,29]
Images from the CDC (inset; adapted) and the CDC/James Gathany (main).
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
Main image: Two petri dish culture plates grow bacteria in the presence of different antibiotic-containing discs. The bacterial isolate on the left plate was susceptible to the antibiotics on the discs and, therefore, was unable to grow adjacent to the discs. The plate on the right was inoculated with a CRE bacterium that proved to be resistant to all of the antibiotics tested and was thus able to grow near the discs. Top center inset: 3D computer-generated image of a group of CRE bacteria.
CRE often acquire resistance to several classes of antibiotics, thus susceptibility testing is vital to guide antimicrobial therapy.[30] These pathogens are occasionally susceptible to quinolones and SMX/TMP. However, more reliable treatment options, often in combination, include ceftazidime/avibactam (except when the CRE is of the NDM strain), polymixins, aminoglycosides, or tigecyline.[30] Fosfomycin can be used to treat UTIs.[17,21,30]
Images from Emre JC, Baysak A, Oz AT, Ece G, Arda B, Bacakoglu F. Pan Afr Med J. 2014;17:49. [Open access.] PMID: 25018799, PMCID: PMC4085949.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
The chest radiograph (left) and high-resolution CT (HRCT) scan (right) were obtained in a patient who suffered VRE bacteremia during hospital recovery from Pneumocystis jiroveci pneumonia, granulocystic sarcoma, and acute respiratory distress syndrome (ARDS). E faecalis was identified from port catheter blood cultures, and the patient was successfully treated with linezolid.
WHO Priority 2: High
Vancomycin-resistant Enterococcus faecium
Enteroccoci are part of the normal intestinal and urogenital flora, but they can colonize the skin.[31] Following exposure to vancomycin, these bacteria can develop resistance to the antibiotic, persisting on the skin and in the environment.[31]
VRE-associated infections are more common in the hospital setting than outside of it[1]; those who are ill and have indwelling urinary or IV catheters are at particular risk.[1,31] VRE can cause SSIs, UTIs, bacteremia, HCAP, and bacterial endocarditis.[31] Of the estimated 66,000 Enterococcus HAIs in the United States each year, almost one third (20,000 [30%]) are caused by VRE, with around 1,300 of these leading to death.[1]
Images from the CDC (left) and the CDC/Pete Wardell (right).
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
Left: Sputum Gram stain obtained from a patient with pneumonia showing Enterococcus spp. Right: Digitally-colorized SEM depicting large numbers of gram-positive E faecalis spp.
Both E faecium and E faecalis can be resistant to vancomycin. About 77% of E faecium isolates are resistant to vancomycin, whereas only 9% of E faecalis isolatesare resistant.[1] Some strains of VRE retain susceptibility to ampicillin, which is the drug of choice for treatment.[32] Other effective agents against VRE include linezolid, daptomycin, and quinupristin-dalfopristin.[31,32] Combination therapy with two or more agents that may include aminoglycosides may be required to treat invasive infections.[31,32]
A new method to structurally modify the cell wall of vancomycin has been developed that, combined with two previous modifications, appears to increase the antibiotic's potency 1,000 fold against enterococci.[33] Under laboratory conditions, this version killed VRE and original enterococcal strains. An attempt to streamline the process of synthesizing the modified vancomycin is in progress.[33]
Images from Gregory Moran, MD, (left) and the CDC (right).
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
These images depict cutaneous abscesses caused by MRSA on the back (left) and the hip (right) in two different patients.
S aureus is a leading source of US HAIs and an important cause of serious infections in the community.[1,34] It can colonize the skin and subsequently cause infections ranging from simple skin and soft-tissue infections to prosthetic device and severe bloodstream infections. Once in the blood, the infection can spread and cause pneumonia, osteomyelitis, or endocarditis, which can be fatal.[34]
Several antibiotics are available to treat MRSA infections; in hospitalized patients, vancomycin therapy has been the most common.[1] This has led to the emergence of strains of S aureus that are intermediately susceptible and resistant to vancomycin (VISA and VRSA, respectively). VISA strains have a vancomycin MIC of 4-8 μg/mL, whereas VRSA strains have a vancomycin MIC of 16 μg/mL and higher.[35]
Images from the National Institute of Allergy and Infectious Diseases (NIAID) (left) and the CDC (right).
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
Left: SEM of MRSA and a dead human neutrophil. Right: 3D computer-generated image of clusters of sphere-shaped VRSA.
All VRSA described to date have acquired the vanA vancomycin-resistance gene that is commonly found in VRE.[35] Intermediate resistance to vancomycin may be related to genes that increase bacterial wall thickness when exposed to the antibiotic, rendering vancomycin less effective.[36] This may improve the ability for the organism to persist in infection, but metabolic costs may decrease the organism's virulence.
If isolates are found to have vancomycin MICs above 2-4 mg/L, it is important to have the laboratory confirm identification of the organism and the MIC, as well as test its susceptibility to daptomycin, linezolid, ceftaroline, and dalbavancin, which are the main alternative agents to vancomycin used in the hospital for treatment of resistant S aureus.[37,38]
Image courtesy of Ed Uthman.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
This is a benign gastric antral ulcer.
Clarithromycin-resistant Helicobacter pylori
H pylori is a spiral-shaped, flagellated bacteria that is found in the gastric mucosa. It produces urease, an enzyme that breaks down urea into ammonia and other chemicals that can directly damage cells and provide a more basic environment in which H pylori can survive.[39]
About 85%-95% of duodenal ulcers and 70%-80% of gastric ulcers are associated with H pylori infection.[40,41] Patients may be asymptomatic, or they may present with gastrointestinal symptoms or peptic ulcer disease. H pylori has also been associated with mucosal-associated lymphoid tissue lymphoma (MALT), gastric cancer, and adenocarcinoma.[41]
Image courtesy of Medscape.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
This image reveals a group of H pylori on immunohistochemistry staining, adherent to the surface of the gastric epithelium (original magnification ×400).
Noninvasive diagnostic studies to detect H pylori include urea breath testing and stool antigen testing. Invasive studies include endoscopy and biopsy of gastrointestinal mucosa, which may show bacterial cells on histology. Biopsy specimens may also be tested for the presence of urease, and tissue cultures may grow the bacteria.
Adapted image from Cerqueira L, Fernandes RM, Ferreira RM, et al. BMC Microbiol. 2011;11:101. [Open access.] PMID: 21569555, PMCID: PMC3112065.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
Peptide nucleic acid-fluorescent in situ hybridization (PNA-FISH) is a potentially new diagnostic method to detect clarithromycin resistance in H pylori smears (shown) and clinical samples. Left: Susceptible strain in the red channel. Center: Resistant strain in the same microscopic field in the green channel. Right: Superimposition of both channels.
H pylori clarithromycin resistance and treatment failure is common in the United States, with an overall resistance prevalence of 32.3% (exceeds the estimated 20% prevalence attributed with successful empiric therapy).[42] Moreover, clarithromycin resistance confers a nearly three-fold increase in treatment failure relative to wildtype H pylori (57.1% vs 19.6%, respectively).[42]
Patients who have been exposed to macrolides or reside in areas where local resistance rates are either over 15% or have clarithromycin eradication rates below 85% should receive a 14-day course of bismuth quadruple therapy (bismuth, metronidazole, tetracycline, proton pump inhibitor [PPI]) or concomitant clarithromycin therapy with amoxicillin, metronidazole, and a PPI.[43] Triple therapy with clarithromycin, a PPI, and either amoxicillin or metronidazole is restricted to areas with low resistance or high eradication success. If therapy fails, patients should undergo repeat endoscopy and tissue biopsy for cultures and susceptibility; they may require other alternative therapies.[43]
Adapted images from CDC medical illustrators Dan Higgins and Jennifer Oosthuizen (left); the CDC (center); and CDC medical illustrator Alissa Eckert (right).
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
3D computer-generated images of drug-resistant Shigella spp (left), drug-resistant Salmonella serotype typhi (center), and drug-resistant Campylobacter spp (right).
Quinolone-resistant Shigella, Salmonella, and Campylobacter
Gram-negative enteric bacteria Shigella, Salmonella, and Campylobacter can cause gastrointestinal illness, usually after exposure to contaminated food and water. Shigella outbreaks among men who have sex with men have also been reported in several regions of the United States (eg, Chicago, Minneapolis, San Francisco, Los Angeles, Portland [Oregon]),[44-46] as well as in the United Kingdom[47-48] and elsewhere.[49-50]
These enteric bacteria have acquired quinolone-resistant genes that can easily be passed from one set of bacteria to another on plasmids or chromosomes.[51] Patients who are infected with resistant pathogens are more likely to have severe infection and be hospitalized.[1]
Images from Fabrega A, du Merle L, Le Bouguenec C, Jimenez de Anta MT, Vila J. PLoS One. 2009;4(11):e8029. [Open access.] PMID: 19946377, PMCID: PMC2777507.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
These micrographs show repression of invasion genes and decreased invasion in two high-level fluoroquinolone-resistant Salmonella typhimurium mutant strains (Giemsa stain).
An estimated 500,000 US Shigella infections occur each year; of these, 27,000 (5.4%) cases are drug-resistant infections, including 12,000 (2.4%) resistant to ciprofloxacin.[1] There are 100,000 cases of drug-resistant non-typhoid Salmonella and 310,000 cases of drug-resistant S typhi cases annually, of which 33,000 (3%) and 3,819 (67%), respectively, have resistance/partial resistance to ciprofloxacin. Of about 1.3 million Campylobacter infections each year, 310,000 (24%) are ciprofloxacin resistant.[1]
Susceptibility testing should be performed on all isolates to guide therapy.[52-58] Patients diagnosed with Shigella or Salmonella without recent travel history outside the United States (especially to Asia) may be treated with a fluoroquinolone. Preferred agents in those with a travel history are ceftriaxone, azithromycin, or SMX/TMP. Patients with Campylobacter infections should be treated with azithromycin; use aminoglycosides or carbapenems for severe Campylobacter infections.[52-58]
Adapted images from the CDC.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
Left: Gonococcal infection involving the cervix. Note the purulent discharge emanating from the cervical os and pooling in the vagina. Right: Cutaneous lesions on the left ankle and calf in a patient with disseminated N gonorrhoeae infection.
Resistant Neisseria gonorrhoeae
N gonorrhoeae is a sexually transmitted infection that can cause cervicitis, urethritis, proctitis, pharyngitis, and pelvic inflammatory disease. Untreated infection can lead to septicemia and to the development of multiorgan involvement, including the skin and joints.[59]
The diagnosis of gonorrhea can be made with nucleic acid amplification testing (NAAT) on cervical, urethral, oropharyngeal, rectal, or urine specimens. Owing to frequent coinfection, obtain studies for Chlamydia trachomatous infection by NAAT, as well screen for human immunodeficiency virus (HIV) and syphilis.[60]
Adapted image from the CDC.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
3D computer-generated image of drug-resistant N gonorrhoeae diplococcal bacteria. Note the hairlike appendages that these bacteria use to promote motility and to improve surface adherence.
Of 820,000 new gonorrhea infections in the United States each year, approximately 246,000 are resistant to one or more antibiotics, particularly tetracycline (188,600 cases).[1] Because the organism has become increasingly resistant to cephalosporins and quinolones, dual therapy with ceftriaxone and azithromycin (preferred) or doxycycline is recommended for patients and their sexual partner(s).[1,59] If resistance is suspected due to its prevalence in the community or owing to a lack of treatment response, obtain cultures to help tailor antibiotic therapy.
Data have shown that two dual-therapy regimens (gentamicin/azithromycin, gemifloxacin/azithromycin) have cure rates of nearly 100% and thus can be used in the setting of ceftriaxone resistance, allergy, or treatment failure.[61]
Image from Chowdhary A, Sharma C, Meis JF. Candida auris: PLoS Pathog. 2017;13(5):e1006290. [Open access.] PMID: 28542486, PMCID: PMC5436850.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
This global map depicts the rapid emergence of MDR C auris strains in five continents.[62] The dates in parentheses denote the year of report of C auris from the respective country or state. In June 2017, the first known cases of C auris in Oman were reported.[63]
Resistant Candida auris
C auris is an emerging global MDR pathogen that has been found to cause severe ear, wound, and bloodstream infections.[64] It has been isolated in respiratory, urinary, biliary, and wound specimens in hospitalized patients and easily contaminates the environment (eg, mattresses/beds, countertops, chairs, infusion pumps).[65] Mortality is high in patients who develop candidemia.[62,64]
In June 2016, the CDC released a clinical alert about the global rise of C auris; within 3 months, the first seven US cases had appeared. As of May 12, 2017, there have been 77 cases across seven US states, with the majority in New York State (53 cases).[65]
Images from (1) Tsay S, Welsh RM, Adams EH, et al. MMWR Morb Mortal Wkly Rep. 2017;66(19):514-5. [Open access.] PMID: 28520710 (bar chart),[65] and (2) the CDC/Shawn Lockhart (petri dish).
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
Bar chart: The seven states from which 77 cases of C auris infection have been reported to the CDC (May 2013 to May 2017).[65]Inset: A strain of C auris cultured in a petri dish.
C auris is often misidentified and, consequently, inappropriately treated.[62,66] Some C auris strains have become resistant to the three main classes of antifungal agents, creating a therapeutic challenge.[64] Thus, treatment may require the use of multiple antifungals, including echinocandins, an antifungal class that US isolates of C auris are most susceptible to.[67]
Patients who are colonized or infected with C auris should be placed on contact precautions, and all cases should be reported to the CDC.[67]
Adapted infographic courtesy of the CDC Antibiotic Resistance (AR) Initiative.
Multidrug Resistant Organisms (MDROs): Growing, Spreading, and Killing
Sharanjeet Thind, MD | June 15, 2017 | Contributor Information
MDROs: General Principles and Recommendations
Prevent infections and spread of resistance[1,68,69]
Perform good hand hygiene practices
Avoid the use of indwelling devices without a clear indication[5]
Place patients with known MDRO infections or with positive surveillance cultures on contact isolation to prevent transmission
Track resistance pathogens[1,68,69]
Implement and support hospital and global surveillance programs of resistant pathogens
Improve the use of antibiotics[1,68,69]
Avoid administering unnecessary antimicrobials
Choose narrow-spectrum antimicrobials when possible
Implement antimicrobial stewardship programs
Seek guidance from infectious disease specialists
Support development of new antimicrobials and diagnostic tests for resistant microorganisms
Bacterial Skin Infections: Can You Make the Diagnosis?
Bacterial skin infections are very common, with presentations ranging from subtle to alarming. Can you correctly identify these lesions? Test your diagnostic acumen with our slideshow.Slideshows, March 2017
Commenting is limited to medical professionals. To comment please Log-in.
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Close
Contributor Information
Author
Sharanjeet Thind, MD
Attending Physician
Department of Internal Medicine/Infectious Diseases
VA Medical Center
Oklahoma City, Oklahoma;
Assistant Professor
Department of Medicine/Infectious Diseases
College of Medicine, University of Oklahoma
Oklahoma City, Oklahoma
Disclosure: Sharanjeet Thind, MD, has disclosed no relevant financial
relationships.
Editor
Olivia Wong, DO
Section Editor
Medscape Drugs & Diseases
New York, New York
Disclosure: Olivia Wong, DO, has disclosed no relevant financial
relationships.
Close
References
Centers for Disease Control and Prevention (CDC). Antibiotic Resistance Threats in the United States, 2013. Atlanta, Ga: CDC; 2013. Publication no CS239559-B. Available at: https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf. Accessed June 2, 2017.
Institute of Medicine (US) Forum on Emerging Infections; Harrison PF, Lederberg J, eds. Antimicrobial Resistance: Issues and Options: Workshop Report. Washington, DC: National Academies Press (US); 1998. PMID: 23035315
Centers for Disease Control and Prevention. Infection control. Management of multidrug-resistant organisms in healthcare settings (2006). II. Background. Updated: November 5, 2015. Available at: https://www.cdc.gov/infectioncontrol/guidelines/mdro/background.html. Accessed June 2, 2017.
Ben-Ami R, Rodriguez-Bano J, Arslan H, et al. A multinational survey of risk factors for infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae in nonhospitalized patients. Clin Infect Dis. 2009 Sep 1;49(5):682-90. PMID: 19622043
World Health Organization. WHO updates Essential Medicines List with new advice on use of antibiotics, and adds medicines for hepatitis C, HIV, tuberculosis and cancer [news release]. June 6, 2017. Available at: http://www.who.int/mediacentre/news/releases/2017/essential-medicines-list/en/. Accessed June 6, 2017.
Howard A, O'Donoghue M, Feeney A, Sleator RD. Acinetobacter baumannii: an emerging opportunistic pathogen. Virulence. 2012 May 1;3(3):243-50. PMID: 22546906
Neonakis IK, Spandidos DA, Petinaki E. Confronting multidrug-resistant Acinetobacter baumannii: a review. Int J Antimicrob Agents. 2011 Feb;37(2):102-9. PMID: 21130607
Weiner LM, Webb AK, Limbago B. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011-2014. Infect Control Hosp Epidemiol. 2016 Nov;37(11):1288-1301. PMID: 27573805
Morrow BJ, Pillar CM, Deane J, et al. Activities of carbapenem and comparator agents against contemporary US Pseudomonas aeruginosa isolates from the CAPITAL surveillance program. Diagn Microbiol Infect Dis. 2013 Apr;75(4):412-6. PMID: 23391609
Shaikh S, Fatima J, Shakil S, Rizvi SM, Kamal MA. Antibiotic resistance and extended spectrum beta-lactamases: types, epidemiology and treatment. Saudi J Biol Sci. 2015 Jan;22(1):90-101. PMID: 25561890
Pfaller MA, Segreti J. Overview of the epidemiological profile and laboratory detection of extended-spectrum beta-lactamases. Clin Infect Dis. 2006 Apr 15;42 suppl 4:S153-63. PMID: 16544266
Logan LK, Meltzer LA, McAuley JB, et al. Extended-spectrum β-lactamase-producing Enterobacteriaceae infections in children: a two-center case-case-control study of risk factors and outcomes in Chicago, Illinois. J Pediatric Infect Dis Soc. 2014 Dec;3(4):312-9. PMID: 26625451
D'Angelo RG, Johnson JK, Bork JT, Heil EL. Treatment options for extended-spectrum beta-lactamase (ESBL) and AmpC-producing bacteria. Expert Opin Pharmacother. 2016;17(7):953-67. PMID: 26891857
Garau J. Other antimicrobials of interest in the era of extended-spectrum beta-lactamases: fosfomycin, nitrofurantoin and tigecycline. Clin Microbiol Infect. 2008 Jan;14 suppl 1:198-202. PMID: 18154548
van Duin D, Bonomo RA. Ceftazidime/avibactam and ceftolozane/tazobactam: second-generation β-lactam/β-lactamase inhibitor combinations. Clin Infect Dis. 2016 Jul 15;63(2):234-41. PMID: 27098166
Diene SM, Rolain JM. Carbapenemase genes and genetic platforms in gram-negative bacilli: Enterobacteriaceae, Pseudomonas and Acinetobacter species. Clin Microbiol Infect. 2014 Sep;20(9):831-8. PMID: 24766097
Centers for Disease Control and Prevention (CDC). Facility Guidance for Control of Carbapenem-resistant Enterobacteriaceae (CRE) – November 2015 Update CRE Toolkit. Atlanta, Ga: CDC; 2015. Publication no CS261687-A. Available at: https://www.cdc.gov/hai/organisms/cre/cre-toolkit/index.html. Accessed June 7, 2017.
Levy Hara G, Gould I, Endimiani A, et al. Detection, treatment, and prevention of carbapenemase-producing Enterobacteriaceae: recommendations from an International Working Group. J Chemother. 2013 Jun;25(3):129-40. PMID: 23783137
Gupta N, Limbago BM, Patel JB, Kallen AJ. Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention. Clin Infect Dis. 2011 Jul 1;53(1):60-7. PMID: 21653305
World Health Organization. Antimicrobial resistance: revisiting the “tragedy of the commons”. Bull World Health Organ. 2010 Nov 1;88(11):805-6. PMID: 21076559
Maurer FP, Castelberg C, Quiblier C, Bloemberg GV, Hombach M. Evaluation of carbapenemase screening and confirmation tests with Enterobacteriaceae and development of a practical diagnostic algorithm. J Clin Microbiol. 2015 Jan;53(1):95-104. PMID: 25355766
Morrill HJ, Pogue JM, Kaye KS, LaPlante KL. Treatment options for carbapenem-resistant Enterobacteriaceae infections. Open Forum Infect Dis. 2015 May 5;2(2):ofv050. PMID: 26125030
Miller WR, Murray BE, Rice LB, Arias CA. Vancomycin-resistant enterococci: therapeutic challenges in the 21st century. Infect Dis Clin North Am. 2016 Jun;30(2):415-39. PMID: 27208766
Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler VG Jr. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev. 2015 Jul;28(3):603-61. PMID: 26016486
Walters M, Lonsway D, Rasheed K, et al. Investigation and Control of Vancomycin-Resistant Staphylococcus aureus (VRSA): 2015 Update. Atlanta, Ga: Centers for Disease Control and Prevention; 2015. Available at: https://www.cdc.gov/hai/pdfs/vrsa-investigation-guide-05_12_2015.pdf. Accessed June 7, 2017.
Gardete S, Tomasz A. Mechanisms of vancomycin resistance in Staphylococcus aureus. J Clin Invest. 2014 Jul;124(7):2836-40. PMID: 24983424
Liu C, Bayer A, Cosgrove SE, for the Infectious Diseases Society of America. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Feb 1;52(3):e18-55. PMID: 21208910
Morales-Cartagena A, Lalueza A, Lopez-Medrano F, San Juan R, Aguado JM. Treatment of methicillin-resistant Staphylococcus aureus infections: importance of high vancomycin minumum inhibitory concentrations. World J Clin Infect Dis. 2015 May 25;5(2):14-29. Available at: http://www.wjgnet.com/2220-3176/full/v5/i2/14.htm. Accessed June 7, 2017.
Mobley HL. The role of Helicobacter pylori urease in the pathogenesis of gastritis and peptic ulceration. Aliment Pharmacol Ther. 1996 Apr;10 suppl 1:57-64. PMID: 8730260
Ford AC, Gurusamy KS, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people. Cochrane Database Syst Rev. 2016 Apr 19;4:CD003840. PMID: 27092708
Talebi Bezmin Abadi A, Perez-Perez G. Role of dupA in virulence of Helicobacter pylori. World J Gastroenterol. 2016 Dec 14;22(46):10118-10123. PMID: 28028359
Park JY, Dunbar KB, Mitui M, et al. Helicobacter pylori clarithromycin resistance and treatment failure are common in the USA. Dig Dis Sci. 2016 Aug;61(8):2373-80. PMID: 26923948
Fallone CA, Chiba N, van Zanten SV, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology. 2016 Jul;151(1):51-69.e14. PMID: 27102658
Bowen A, Eikmeier D, Talley P, et al, for the Centers for Disease Control and Prevention. Notes from the field: outbreaks of Shigella sonnei infection with decreased susceptibility to azithromycin among men who have sex with men - Chicago and Metropolitan Minneapolis-St. Paul, 2014. MMWR Morb Mortal Wkly Rep. 2015 Jun 5;64(21):597-8. PMID: 26042652
Hines JZ, Pinsent T, Rees K, et al. Notes from the field: shigellosis outbreak among men who have sex with men and homeless persons - Oregon, 2015-2016. MMWR Morb Mortal Wkly Rep. 2016 Aug 12;65(31):812-3. PMID: 27513523
Bowen A, Grass J, Bicknese A, Campbell D, Hurd J, Kirkcaldy RD. Elevated risk for antimicrobial drug-resistant Shigella Infection among men who have sex with men, United States, 2011-2015. Emerg Infect Dis. 2016 Sep;22(9):1613-6. PMID: 27533624
Cresswell FV, Ross S, Booth T, et al. Shigella flexneri: a cause of significant morbidity and associated with sexually transmitted infections in men who have sex with men. Sex Transm Dis. 2015 Jun;42(6):344. PMID: 25970314
Baker KS, Dallman TJ, Ashton PM, et al. Intercontinental dissemination of azithromycin-resistant shigellosis through sexual transmission: a cross-sectional study. Lancet Infect Dis. 2015 Aug;15(8):913-21. PMID: 25936611
Liao YS, Liu YY, Lo YC, Chiou CS. Azithromycin-nonsusceptible Shigella flexneri 3a in men who have sex with men, Taiwan, 2015-2016. Emerg Infect Dis. 2016 Feb;23(2):345-6. PMID: 28098533
Lane CR, Sutton B, Valcanis M, et al. Travel destinations and sexual behavior as indicators of antibiotic resistant Shigella strains--Victoria, Australia. Clin Infect Dis. 2016 Mar 15;62(6):722-729. PMID: 26679624
Rodriguez-Martinez JM, Machuca J, Cano ME, Calvo J, Martinez-Martinez L, Pascual A. Plasmid-mediated quinolone resistance: two decades on. Drug Resist Updat. 2016 Nov;29:13-29. PMID: 27912841
Nuesch-Inderbinen M, Heini N, Zurfluh K, Althaus D, Hachler H, Stephan R. Shigella antimicrobial drug resistance mechanisms, 2004-2014. Emerg Infect Dis. 2016 Jun;22(6):1083-5. PMID: 27191035
Bowen A, Hurd J, Hoover C, et al, for the Centers for Disease Control and Prevention. Importation and domestic transmission of Shigella sonnei resistant to ciprofloxacin - United States, May 2014-February 2015. MMWR Morb Mortal Wkly Rep. 2015 Apr 3;64(12):318-20. PMID: 25837241
McDermott PF, Bodeis SM, Aarestrup FM, et al. Development of a standardized susceptibility test for Campylobacter with quality-control ranges for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem. Microb Drug Resist. 2004 Summer;10(2):124-31. PMID: 15256027
Streit JM, Jones RN, Toleman MA, Stratchounski LS, Fritsche TR. Prevalence and antimicrobial susceptibility patterns among gastroenteritis-causing pathogens recovered in Europe and Latin America and Salmonella isolates recovered from bloodstream infections in North America and Latin America: report from the SENTRY Antimicrobial Surveillance Program (2003). Int J Antimicrob Agents. 2006 May;27(5):367-75. PMID: 16647842
Dupont HL. Shigella species (bacillary dysentery). In: Mandell G, Bennett J, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Churchill Livingstone-Elsevier; 2010: chapter 224.
Pegues DA, Miller SI. Salmonella species, including Salmonella typhi. In: Mandell G, Bennett J, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Churchill Livingstone-Elsevier; 2010: chapter 223.
Allos BM, Blaser MJ. Campylobacter jejuni and related species. In: Mandell G, Bennett J, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Churchill Livingstone-Elsevier; 2010: chapter 216.
Centers for Disease Control and Prevention. 2015 Sexually transmitted diseases treatment guidelines. Gonococcal infections. Updated: July 27, 2016. Available at: https://www.cdc.gov/std/tg2015/gonorrhea.htm. Accessed June 8, 2017.
Papp JR, Schachter Ju, Gaydos CA, Van Der Pol B. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae--2014. MMWR Recomm Rep. 2014 Mar 14;63(RR-02):1-19. PMID: 24622331
Kirkcaldy RD, Weinstock HS, Moore PC, et al. The efficacy and safety of gentamicin plus azithromycin and gemifloxacin plus azithromycin as treatment of uncomplicated gonorrhea. Clin Infect Dis. 2014 Oct 15;59(8):1083-91. PMID: 25031289
Chowdhary A, Sharma C, Meis JF. Candida auris: a rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLoS Pathog. 2017 May 18;13(5):e1006290. PMID: 28542486,
Al-Siyabi T, Al Busaidi I, Balkhair A, Muharrmi ZA, Al-Salti M, Al'Adawi B. First report of Candida auris in Oman: clinical and microbiological description of five candidemia cases. J Infect. 2017 Jun 1. PMID: 28579303
Tsay S, Welsh RM, Adams EH, et al, Notes from the field: ongoing transmission of Candida auris in health care facilities - United States, June 2016-May 2017. MMWR Morb Mortal Wkly Rep. 2017 May 19;66(19):514-5. PMID: 28520710
Kordalewska M, Zhao Y, Lockhart SR, Chowdhary A, Berrio I, Perlin DS. Rapid and accurate molecular identification of the emerging multidrug resistant pathogen Candida auris. J Clin Microbiol. 2017 May 24. PMID: 28539346
Centers for Disease Control and Prevention. Fungal diseases. Candida auris interim recommendations for healthcare facilities and laboratories. Updated: May 18, 2017. Available at: https://www.cdc.gov/fungal/diseases/candidiasis/recommendations.html. Accessed June 8, 2017.
Please do not use this form to submit personal or patient medical information or to report adverse drug events. You are encouraged to report adverse drug event information to the FDA.
Comments