- Email: [email protected]
Vancomycin-Resistant Staphylococcus aureus—Delaware, 2015
INFECTIOUS DISEASE/CDC UPDATE
Update on Emerging Infections: News From the Centers for Disease Control and Prevention Commentators Mustapha Saheed, MD; Richard Rothman, MD, PhD
Editor’s note: This article is part of a regular series on emerging infection from the Centers for Disease Control and Prevention (CDC) and the EMERGEncy ID NET, an emergency department–based and CDC-collaborative surveillance network. Important infectious disease public health information with relevance to emergency physicians is reported. The goal of this series is to advance knowledge about communicable diseases in emergency medicine and foster cooperation between the front line of clinical medicine and public health agencies.
Vancomycin-Resistant Staphylococcus aureus— Delaware, 2015 [Walters MS, Eggers P, Albrecht V, et al. Vancomycin-resistant Staphylococcus aureus— Delaware, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:1056.] Vancomycin-resistant Staphylococcus aureus (VRSA) is a rare, multidrug-resistant bacterium of public health concern that emerged in the United States in 2002. It arises (S aureus with vancomycin minimum inhibitory concentration 16 mg/mL) when vancomycin resistance genes (eg, the vanA operon, which codes for enzymes that result in modification or elimination of the vancomycinbinding site) from vancomycin-resistant enterococci (VRE) are transferred to S aureus.1 To date, all VRSA strains have arisen from methicillin-resistant S aureus (MRSA). The 14th VRSA isolate (VRSA 14) identified in the United States was reported to the Centers for Disease Control and Prevention (CDC) in February 2015. VRSA 14 was cultured from the chronic toe wound of a patient in Delaware, who had diabetes mellitus and endstage renal disease requiring hemodialysis; vancomycinresistant Enterococcus faecalis was also isolated from this culture. The wound was first noted during an inpatient admission in April 2014. MRSA was isolated in August and October 2014, and MRSA and VRE were isolated in January 2015; these isolates are not available for further characterization. No antibiotic use was reported in the 4 months before VRSA isolation. The VRSA and VRE toe wound isolates (February 2015) and an MRSA isolate from a nasal swab from the patient 386 Annals of Emergency Medicine
(March 2015) were sent to CDC for further characterization. The VRSA and VRE were confirmed to be resistant to vancomycin (minimum inhibitory concentrations¼512 mg/ mL for both); polymerase chain reaction testing confirmed the presence of vanA in both isolates. Pulsed-field gel electrophoresis and S aureus protein A (spa) typing identified both the VRSA and MRSA as types USA100 and t002, placing them in staphylococcal clonal complex 5. This indicates that VRSA 14 has a health care–associated strain background, as do VRSA 1 to 12. Among VRSA isolated in the United States, only VRSA 13 had a communityassociated strain background.2 Persons considered to be at increased risk for VRSA acquisition were health care providers at the wound clinic and the dialysis clinic and dialysis patients sharing the same dialysis shift as the VRSA patient. Three of 6 wound clinic health care workers, all 13 dialysis clinic workers, and the 3 health care providers who evaluated the wound at an outpatient clinic consented to groin and nasal swab surveillance cultures. Twelve of 13 patients who shared a dialysis shift with the VRSA patient consented to nasal swabs. No MRSA, VRSA, or VRE was cultured from the health care workers or dialysis patients, indicating that close contacts did not share precursor organisms or VRSA with the patient. To facilitate immediate use of contact precautions in the event the patient presented for care, Delaware public health authorities notified facilities where the patient routinely sought health care. The last 4 VRSA isolates confirmed by CDC have been isolated from patients in Delaware. All 14 VRSA identified in the United States appear to have independently acquired the vanA operon. Transmission of VRSA beyond the index patients has not been detected. However, VRSA isolates arise from highly transmissible MRSA progenitor strains, and a robust public health response to all reported VRSA is recommended. Guidelines for VRSA investigation were revised in 2015 and are available at http://www.cdc.gov/hai/pdfs/vrsainvestigation-guide-05_12_2015.pdf. Isolation of suspected or confirmed VRSA should be reported immediately through state and local health departments (eg, the state antibiotic resistance program coordinator) to Volume 67, no. 3 : March 2016
CDC Update
CDC’s Division of Healthcare Quality Promotion ([email protected]). Section editors: David A. Talan, MD; Gregory J. Moran, MD; Satish K. Pillai, MD, MPH; Scott Santibanez, MD, MPHTM Author affiliations: From the Department of Emergency Medicine, Johns Hopkins University, Baltimore, MD. http://dx.doi.org/10.1016/j.annemergmed.2015.12.017
REFERENCES 1. Zhu W, Clark N, Patel JB. pSK41-like plasmid is necessary for Inc18-like vanA plasmid transfer from Enterococcus faecalis to Staphylococcus aureus in vitro. Antimicrob Agents Chemother. 2013;57:212-219. 2. Limbago BM, Kallen AJ, Zhu W, et al. Report of the 13th vancomycinresistant Staphylococcus aureus isolate from the United States. J Clin Microbiol. 2014;52:998-1002.
COMMENTARY [Ann Emerg Med. 2016;67:387-388.] In the 1940s, S aureus was uniformly susceptible to penicillin. Within a few years, penicillin-resistant isolates were identified, and by the 1970s MRSA had emerged.1 MRSA is now one of the most common causes of hospitaland community-acquired infections, accounting for the majority of skin and soft tissue infections that present to the emergency department (ED).2 High-level VRSA remains rare, so there is no need to discontinue using vancomycin as our first-line parenteral agent for suspected MRSA infections. However, the report of an additional VRSA isolate in the United States is an important sentinel for emergency providers whose practices can greatly affect the emergence and spread of resistant organisms. Vancomycin inhibits cell-wall synthesis and disrupts bacterial replication by binding to a highly preserved binding site, D-ala-D-ala, on peptidoglycan precursors, which are basic building blocks of bacterial cell walls.3 Processes that interfere with vancomycin binding directly reduce the drug’s efficacy. S aureus strains with intermediate resistance to vancomycin (VISA) were first identified in the early 1990s in Japan and have since spread globally.4 VISA strains evolve from sequential mutations and use varied biochemical and morphologic mechanisms to reduce vancomycin efficacy.3,4 As an example, some VISA strains have a thickened cell wall that reduces vancomycin diffusion to its binding site on the cytoplasmic membrane.3 Others have significantly reduced growth rates, which counteracts the increased vancomycin sensitivity that occurs during cellular division.3 Fortuitously, most VISA-resistance mechanisms are nontransferable and come with significant Volume 67, no. 3 : March 2016
“fitness” costs to the organism, limiting overall strain pathogenicity.3 VRSA was first reported in the United States in 2002, and, as noted in the accompanying report, there have been only 14 cases reported to date. VRSA evolved through a different mechanism than VISA; MRSA strains gained plasmid-mediated resistance genes from vancomycinresistant enterococci (VRE) species. Plasmids, small circular extrachromosomal DNA that replicate independently, can be transferred through bacterial conjugative processes across different bacterial species. This type of resistance is mediated through genetic mutations but spread through breakdowns in infection control. The vanA operon gene, contained on the plasmid, codes for enzymes that change the binding site of vancomycin to D-ala-D-lactate, reducing vancomycin affinity up to 1000-fold.5 Although the total number of VRSA cases to date is small, the potential for dissemination is real. One particularly concerning finding is a report describing VRSA transformation of a community-acquired MRSA strain, increasing the likelihood of the emergence of a communitybased epidemic, similar to what was observed with MRSA.6 There is overwhelming evidence that curbing inappropriate antibiotic usage results in reduced resistance rates and associated comorbidities, such as Clostridium difficile infection.7 With regard to vancomycin use in the ED, one ED-based observational study conducted in 2008 to 2010 identified the frequent and questionably effective practice of administration of a single dose of vancomycin before patient discharge with oral antibiotics, as well as frequent vancomycin underdosing.8 For treatment of most nonobese patients with normal renal function who have skin and soft tissue infections severe enough to require hospital admission, standard vancomycin dosing of 1 g every 12 hours is recommended. However, for other syndromes, such as severe sepsis and pneumonia in which MRSA is suspected, weight-based dosing of 15 to 20 mg/kg per dose with monitoring of trough levels is recommended, and, for critically ill patients, this would be preceded by an initial loading dose of 25 to 30 mg/kg (actual body weight).9 MRSA coverage is not recommended for nonpurulent skin and soft tissue infections such as cellulitis.10 Although many of the successful strategies that lead to a reduction in inappropriate antibiotic prescribing have not yet been systematically evaluated in the ED, the conceptual framework for an ED-focused strategy has been put forward.11 Key approaches include implementation of physician antibiotic education programs, development and dissemination of ED-specific guidelines, implementation of ED-based clinical pharmacy programs, and use of clinical Annals of Emergency Medicine 387
Update on Emerging Infections: News From the Centers for Disease Control and Prevention Commentators Mustapha Saheed, MD; Richard Rothman, MD, PhD
Editor’s note: This article is part of a regular series on emerging infection from the Centers for Disease Control and Prevention (CDC) and the EMERGEncy ID NET, an emergency department–based and CDC-collaborative surveillance network. Important infectious disease public health information with relevance to emergency physicians is reported. The goal of this series is to advance knowledge about communicable diseases in emergency medicine and foster cooperation between the front line of clinical medicine and public health agencies.
Vancomycin-Resistant Staphylococcus aureus— Delaware, 2015 [Walters MS, Eggers P, Albrecht V, et al. Vancomycin-resistant Staphylococcus aureus— Delaware, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:1056.] Vancomycin-resistant Staphylococcus aureus (VRSA) is a rare, multidrug-resistant bacterium of public health concern that emerged in the United States in 2002. It arises (S aureus with vancomycin minimum inhibitory concentration 16 mg/mL) when vancomycin resistance genes (eg, the vanA operon, which codes for enzymes that result in modification or elimination of the vancomycinbinding site) from vancomycin-resistant enterococci (VRE) are transferred to S aureus.1 To date, all VRSA strains have arisen from methicillin-resistant S aureus (MRSA). The 14th VRSA isolate (VRSA 14) identified in the United States was reported to the Centers for Disease Control and Prevention (CDC) in February 2015. VRSA 14 was cultured from the chronic toe wound of a patient in Delaware, who had diabetes mellitus and endstage renal disease requiring hemodialysis; vancomycinresistant Enterococcus faecalis was also isolated from this culture. The wound was first noted during an inpatient admission in April 2014. MRSA was isolated in August and October 2014, and MRSA and VRE were isolated in January 2015; these isolates are not available for further characterization. No antibiotic use was reported in the 4 months before VRSA isolation. The VRSA and VRE toe wound isolates (February 2015) and an MRSA isolate from a nasal swab from the patient 386 Annals of Emergency Medicine
(March 2015) were sent to CDC for further characterization. The VRSA and VRE were confirmed to be resistant to vancomycin (minimum inhibitory concentrations¼512 mg/ mL for both); polymerase chain reaction testing confirmed the presence of vanA in both isolates. Pulsed-field gel electrophoresis and S aureus protein A (spa) typing identified both the VRSA and MRSA as types USA100 and t002, placing them in staphylococcal clonal complex 5. This indicates that VRSA 14 has a health care–associated strain background, as do VRSA 1 to 12. Among VRSA isolated in the United States, only VRSA 13 had a communityassociated strain background.2 Persons considered to be at increased risk for VRSA acquisition were health care providers at the wound clinic and the dialysis clinic and dialysis patients sharing the same dialysis shift as the VRSA patient. Three of 6 wound clinic health care workers, all 13 dialysis clinic workers, and the 3 health care providers who evaluated the wound at an outpatient clinic consented to groin and nasal swab surveillance cultures. Twelve of 13 patients who shared a dialysis shift with the VRSA patient consented to nasal swabs. No MRSA, VRSA, or VRE was cultured from the health care workers or dialysis patients, indicating that close contacts did not share precursor organisms or VRSA with the patient. To facilitate immediate use of contact precautions in the event the patient presented for care, Delaware public health authorities notified facilities where the patient routinely sought health care. The last 4 VRSA isolates confirmed by CDC have been isolated from patients in Delaware. All 14 VRSA identified in the United States appear to have independently acquired the vanA operon. Transmission of VRSA beyond the index patients has not been detected. However, VRSA isolates arise from highly transmissible MRSA progenitor strains, and a robust public health response to all reported VRSA is recommended. Guidelines for VRSA investigation were revised in 2015 and are available at http://www.cdc.gov/hai/pdfs/vrsainvestigation-guide-05_12_2015.pdf. Isolation of suspected or confirmed VRSA should be reported immediately through state and local health departments (eg, the state antibiotic resistance program coordinator) to Volume 67, no. 3 : March 2016
CDC Update
CDC’s Division of Healthcare Quality Promotion ([email protected]). Section editors: David A. Talan, MD; Gregory J. Moran, MD; Satish K. Pillai, MD, MPH; Scott Santibanez, MD, MPHTM Author affiliations: From the Department of Emergency Medicine, Johns Hopkins University, Baltimore, MD. http://dx.doi.org/10.1016/j.annemergmed.2015.12.017
REFERENCES 1. Zhu W, Clark N, Patel JB. pSK41-like plasmid is necessary for Inc18-like vanA plasmid transfer from Enterococcus faecalis to Staphylococcus aureus in vitro. Antimicrob Agents Chemother. 2013;57:212-219. 2. Limbago BM, Kallen AJ, Zhu W, et al. Report of the 13th vancomycinresistant Staphylococcus aureus isolate from the United States. J Clin Microbiol. 2014;52:998-1002.
COMMENTARY [Ann Emerg Med. 2016;67:387-388.] In the 1940s, S aureus was uniformly susceptible to penicillin. Within a few years, penicillin-resistant isolates were identified, and by the 1970s MRSA had emerged.1 MRSA is now one of the most common causes of hospitaland community-acquired infections, accounting for the majority of skin and soft tissue infections that present to the emergency department (ED).2 High-level VRSA remains rare, so there is no need to discontinue using vancomycin as our first-line parenteral agent for suspected MRSA infections. However, the report of an additional VRSA isolate in the United States is an important sentinel for emergency providers whose practices can greatly affect the emergence and spread of resistant organisms. Vancomycin inhibits cell-wall synthesis and disrupts bacterial replication by binding to a highly preserved binding site, D-ala-D-ala, on peptidoglycan precursors, which are basic building blocks of bacterial cell walls.3 Processes that interfere with vancomycin binding directly reduce the drug’s efficacy. S aureus strains with intermediate resistance to vancomycin (VISA) were first identified in the early 1990s in Japan and have since spread globally.4 VISA strains evolve from sequential mutations and use varied biochemical and morphologic mechanisms to reduce vancomycin efficacy.3,4 As an example, some VISA strains have a thickened cell wall that reduces vancomycin diffusion to its binding site on the cytoplasmic membrane.3 Others have significantly reduced growth rates, which counteracts the increased vancomycin sensitivity that occurs during cellular division.3 Fortuitously, most VISA-resistance mechanisms are nontransferable and come with significant Volume 67, no. 3 : March 2016
“fitness” costs to the organism, limiting overall strain pathogenicity.3 VRSA was first reported in the United States in 2002, and, as noted in the accompanying report, there have been only 14 cases reported to date. VRSA evolved through a different mechanism than VISA; MRSA strains gained plasmid-mediated resistance genes from vancomycinresistant enterococci (VRE) species. Plasmids, small circular extrachromosomal DNA that replicate independently, can be transferred through bacterial conjugative processes across different bacterial species. This type of resistance is mediated through genetic mutations but spread through breakdowns in infection control. The vanA operon gene, contained on the plasmid, codes for enzymes that change the binding site of vancomycin to D-ala-D-lactate, reducing vancomycin affinity up to 1000-fold.5 Although the total number of VRSA cases to date is small, the potential for dissemination is real. One particularly concerning finding is a report describing VRSA transformation of a community-acquired MRSA strain, increasing the likelihood of the emergence of a communitybased epidemic, similar to what was observed with MRSA.6 There is overwhelming evidence that curbing inappropriate antibiotic usage results in reduced resistance rates and associated comorbidities, such as Clostridium difficile infection.7 With regard to vancomycin use in the ED, one ED-based observational study conducted in 2008 to 2010 identified the frequent and questionably effective practice of administration of a single dose of vancomycin before patient discharge with oral antibiotics, as well as frequent vancomycin underdosing.8 For treatment of most nonobese patients with normal renal function who have skin and soft tissue infections severe enough to require hospital admission, standard vancomycin dosing of 1 g every 12 hours is recommended. However, for other syndromes, such as severe sepsis and pneumonia in which MRSA is suspected, weight-based dosing of 15 to 20 mg/kg per dose with monitoring of trough levels is recommended, and, for critically ill patients, this would be preceded by an initial loading dose of 25 to 30 mg/kg (actual body weight).9 MRSA coverage is not recommended for nonpurulent skin and soft tissue infections such as cellulitis.10 Although many of the successful strategies that lead to a reduction in inappropriate antibiotic prescribing have not yet been systematically evaluated in the ED, the conceptual framework for an ED-focused strategy has been put forward.11 Key approaches include implementation of physician antibiotic education programs, development and dissemination of ED-specific guidelines, implementation of ED-based clinical pharmacy programs, and use of clinical Annals of Emergency Medicine 387