Risk of Vascular Access Infection Associated With Buttonhole Cannulation of Fistulas: Data From the National Healthcare Safety Network.

RATIONALE & OBJECTIVE: Compared with conventional (rope-ladder cannulation [RLC]) methods, use of buttonhole cannulation (BHC) to access arteriovenous fistulas (AVFs) may be associated with increased risk for bloodstream infection and other vascular access-related infection. We used national surveillance data to evaluate the infection burden and risk among in-center hemodialysis patients with AVFs using BHC. STUDY DESIGN: Descriptive analysis of infections and related events and retrospective observational cohort study using National Healthcare Safety Network (NHSN) surveillance data. SETTING & PARTICIPANTS: US patients receiving hemodialysis treated in outpatient dialysis centers. PREDICTORS: AVF cannulation methods, dialysis facility characteristics, and infection control practices. OUTCOMES: Access-related bloodstream infection; local access-site infection; intravenous (IV) antimicrobial start. ANALYTIC APPROACH: Description of frequency and rate of infections; adjusted relative risk (aRR) for infection with BHC versus RLC estimated using Poisson regression. RESULTS: During 2013 to 2014, there were 2,466 access-related bloodstream infections, 3,169 local access-site infections, and 13,726 IV antimicrobial starts among patients accessed using BHC. Staphylococcus aureus was the most common pathogen, present in half (52%) of the BHC access-related bloodstream infections. Hospitalization was frequent among BHC access-related bloodstream infections (37%). In 2014, 9% (n=271,980) of all AVF patient-months reported to NHSN were associated with BHC. After adjusting for facility characteristics and practices, BHC was associated with significantly higher risk for access-related bloodstream infection (aRR, 2.6; 95% CI, 2.4-2.8) and local access-site infection (aRR, 1.5; 95% CI, 1.4-1.6) than RLC, but was not associated with increased risk for IV antimicrobial start. LIMITATIONS: Data for facility practices were self-reported and not patient specific. CONCLUSIONS: BHC was associated with higher risk for vascular access-related infection than RLC among in-center hemodialysis patients. Decisions regarding the use of BHC in dialysis centers should take into account the higher risk for infection. Studies are needed to evaluate infection control measures that may reduce infections related to BHC.

Transmission of hepatitis C virus in the dialysis setting and strategies for its prevention.

Hepatitis C virus (HCV) infection is more common among hemodialysis patients than the general population and transmission of HCV in dialysis clinics has been reported. In the context of the increased morbidity and mortality associated with HCV infection in the end stage renal disease population, it is important that dialysis clinics have processes in place for ensuring recommended infection control practices, including Standard Precautions, through regular audits and training of the staff. This review will summarize the epidemiology of HCV infection and risk factors for HCV transmission among hemodialysis patients. In addition, the proper protocols are required to investigate suspected cases of HCV transmission in dialysis facilities and recommendations for prevention of HCV transmission in will be reviewed.

Multistate US Outbreak of Rapidly Growing Mycobacterial Infections Associated with Medical Tourism to the Dominican Republic, 2013-2014(1).

During 2013, the Maryland Department of Health and Mental Hygiene in Baltimore, MD, USA, received report of 2 Maryland residents whose surgical sites were infected with rapidly growing mycobacteria after cosmetic procedures at a clinic (clinic A) in the Dominican Republic. A multistate investigation was initiated; a probable case was defined as a surgical site infection unresponsive to therapy in a patient who had undergone cosmetic surgery in the Dominican Republic. We identified 21 case-patients in 6 states who had surgery in 1 of 5 Dominican Republic clinics; 13 (62%) had surgery at clinic A. Isolates from 12 (92%) of those patients were culture-positive for Mycobacterium abscessus complex. Of 9 clinic A case-patients with available data, all required therapeutic surgical intervention, 8 (92%) were hospitalized, and 7 (78%) required ≥3 months of antibacterial drug therapy. Healthcare providers should consider infection with rapidly growing mycobacteria in patients who have surgical site infections unresponsive to standard treatment.

Cluster and sporadic cases of herbaspirillum species infections in patients with cancer.

BACKGROUND: Herbaspirillum species are gram-negative Betaproteobacteria that inhabit the rhizosphere. We investigated a potential cluster of hospital-based Herbaspirillum species infections. METHODS: Cases were defined as Herbaspirillum species isolated from a patient in our comprehensive cancer center between 1 January 2006 and 15 October 2013. Case finding was performed by reviewing isolates initially identified as Burkholderia cepacia susceptible to all antibiotics tested, and 16S ribosomal DNA sequencing of available isolates to confirm their identity. Pulsed-field gel electrophoresis (PFGE) was performed to test genetic relatedness. Facility observations, infection prevention assessments, and environmental sampling were performed to investigate potential sources of Herbaspirillum species. RESULTS: Eight cases of Herbaspirillum species were identified. Isolates from the first 5 clustered cases were initially misidentified as B. cepacia, and available isolates from 4 of these cases were indistinguishable. The 3 subsequent cases were identified by prospective surveillance and had different PFGE patterns. All but 1 case-patient had bloodstream infections, and 6 presented with sepsis. Underlying diagnoses included solid tumors (3), leukemia (3), lymphoma (1), and aplastic anemia (1). Herbaspirillum species infections were hospital-onset in 5 patients and community-onset in 3. All symptomatic patients were treated with intravenous antibiotics, and their infections resolved. No environmental source or common mechanism of acquisition was identified. CONCLUSIONS: This is the first report of a hospital-based cluster of Herbaspirillum species infections. Herbaspirillum species are capable of causing bacteremia and sepsis in immunocompromised patients. Herbaspirillum species can be misidentified as Burkholderia cepacia by commercially available microbial identification systems.

Fungal infections associated with contaminated methylprednisolone in Tennessee.

BACKGROUND: We investigated an outbreak of fungal infections of the central nervous system that occurred among patients who received epidural or paraspinal glucocorticoid injections of preservative-free methylprednisolone acetate prepared by a single compounding pharmacy. METHODS: Case patients were defined as patients with fungal meningitis, posterior circulation stroke, spinal osteomyelitis, or epidural abscess that developed after epidural or paraspinal glucocorticoid injections. Clinical and procedure data were abstracted. A cohort analysis was performed. RESULTS: The median age of the 66 case patients was 69 years (range, 23 to 91). The median time from the last epidural glucocorticoid injection to symptom onset was 18 days (range, 0 to 56). Patients presented with meningitis alone (73%), the cauda equina syndrome or focal infection (15%), or posterior circulation stroke with or without meningitis (12%). Symptoms and signs included headache (in 73% of the patients), new or worsening back pain (in 50%), neurologic symptoms (in 48%), nausea (in 39%), and stiff neck (in 29%). The median cerebrospinal fluid white-cell count on the first lumbar puncture among patients who presented with meningitis, with or without stroke or focal infection, was 648 per cubic millimeter (range, 6 to 10,140), with 78% granulocytes (range, 0 to 97); the protein level was 114 mg per deciliter (range, 29 to 440); and the glucose concentration was 44 mg per deciliter (range, 12 to 121) (2.5 mmol per liter [range, 0.7 to 6.7]). A total of 22 patients had laboratory confirmation of Exserohilum rostratum infection (21 patients) or Aspergillus fumigatus infection (1 patient). The risk of infection increased with exposure to lot 06292012@26, older vials, higher doses, multiple procedures, and translaminar approach to epidural glucocorticoid injection. Voriconazole was used to treat 61 patients (92%); 35 patients (53%) were also treated with liposomal amphotericin B. Eight patients (12%) died, seven of whom had stroke. CONCLUSIONS: We describe an outbreak of fungal meningitis after epidural or paraspinal glucocorticoid injection with methylprednisolone from a single compounding pharmacy. Rapid recognition of illness and prompt initiation of therapy are important to prevent complications. (Funded by the Tennessee Department of Health and the Centers for Disease Control and Prevention.).

Notes from the field: rapidly growing nontuberculous Mycobacterium wound infections among medical tourists undergoing cosmetic surgeries in the Dominican Republic--multiple states, March 2013-February 2014.

In August 2013, the Maryland Department of Health and Mental Hygiene (MDHMH) was notified of two persons with rapidly growing nontuberculous mycobacterial (RG-NTM) surgical-site infections. Both patients had undergone surgical procedures as medical tourists at the same private surgical clinic (clinic A) in the Dominican Republic the previous month. Within 7 days of returning to the United States, both sought care for symptoms that included surgical wound abscesses, clear fluid drainage, pain, and fever. Initial antibiotic therapy was ineffective. Material collected from both patients' wounds grew Mycobacterium abscessus exhibiting a high degree of antibiotic resistance characteristic of this organism.

Investigation of a prolonged Group A Streptococcal outbreak among residents of a skilled nursing facility, Georgia, 2009-2012.

BACKGROUND: Group A Streptococcus (GAS) is an important bacterial cause of life-threatening illness among the elderly. Public health officials investigated a protracted GAS outbreak in a skilled nursing facility in Georgia housing patients requiring 24-hour nursing or rehabilitation, to prevent additional cases. METHODS: We defined a case as illness in a skilled nursing facility resident with onset after January 2009 with GAS isolated from a usually sterile (invasive) or nonsterile site (noninvasive). Cases were "recurrent" if >1 month elapsed between episodes. We evaluated infection control practices, performed a GAS carriage study, emm-typed available GAS isolates, and conducted a case-control study of risk factors for infection. RESULTS: Three investigations, spanning 36 months, identified 19 residents with a total of 24 GAS infections: 15 invasive (3 recurrent) and 9 noninvasive (2 recurrent) episodes. All invasive cases required hospitalization; 4 patients died. Seven residents were GAS carriers. All invasive cases and resident carrier isolates were type emm 11.0. We observed hand hygiene lapses, inadequate infection documentation, and more frequent wound care staff turnover on wing A versus wing B. Risk factors associated with infection in multivariable analysis included living on wing A (odds ratio [OR], 3.4; 95% confidence interval [CI], .9-16.4) and having an indwelling line (OR, 5.6; 95% CI, 1.2-36.4). Cases ceased following facility-wide chemoprophylaxis in July 2012. CONCLUSIONS: Staff turnover, compromised skin integrity in residents, a suboptimal infection control program, and lack of awareness of infections likely contributed to continued GAS transmission. In widespread, prolonged GAS outbreaks in skilled nursing facilities, facility-wide chemoprophylaxis may be necessary to prevent sustained person-to-person transmission.

Invasive methicillin-resistant Staphylococcus aureus infections among patients on chronic dialysis in the United States, 2005-2011.

BACKGROUND: Approximately 15 700 invasive methicillin-resistant Staphylococcus aureus (MRSA) infections occurred in US dialysis patients in 2010. Frequent hospital visits and prolonged bloodstream access, especially via central venous catheters (CVCs), are risk factors among hemodialysis patients. We describe the epidemiology of and recent trends in invasive MRSA infections among dialysis patients. METHODS: We analyzed population-based data from 9 US metropolitan areas from 2005 to 2011. Cases were defined as MRSA isolated from a normally sterile body site in a surveillance area resident who received dialysis, and were classified as hospital-onset (HO; culture collected >3 days after hospital admission) or healthcare-associated community-onset (HACO; all others). Incidence was calculated using denominators from the US Renal Data System. Temporal trends in incidence and national estimates were calculated controlling for age, sex, and race. RESULTS: From 2005 to 2011, 7489 cases were identified; 85.7% were HACO infections, and 93.2% were bloodstream infections. Incidence of invasive MRSA infections decreased from 6.5 to 4.2 per 100 dialysis patients (annual decrease, 7.3%) with annual decreases of 6.7% for HACO and 10.5% for HO cases. Among cases identified during 2009-2011, 70% of patients were hospitalized in the year prior to infection. Among hemodialysis cases, 60.4% of patients were dialyzed through a CVC. The 2011 national estimated number of MRSA infections was 15 169. CONCLUSIONS: There has been a substantial decrease in invasive MRSA infection incidence among dialysis patients. Most cases had previous hospitalizations, suggesting that efforts to control MRSA in hospitals might have contributed to the declines. Infection prevention measures should include improved vascular access and CVC care.

A cluster of gram-negative bloodstream infections in Connecticut hemodialysis patients associated with contaminated wall boxes and prime buckets.

BACKGROUND: Maintenance hemodialysis (HD) patients are at increased risk of bloodstream infections (BSI). We investigated a cluster of Delftia acidovorans infections among patients undergoing HD at an outpatient unit (Facility A). METHODS: A case was defined as a Facility A HD patient with ≥1 culture positive for D acidovorans between February 1 and April 30, 2018. An investigation included review of patient records, facility policies, practice observations, and environmental cultures. RESULTS: The cluster included 2 patients with confirmed D acidovorans BSI. Both patients had recently been dialyzed at Station #2, where a wall box culture yielded D acidovorans. One patient also had a BSI due to Enterobacter asburiae, which was recovered from several other wall boxes and saline prime buckets (SPB). Observations revealed leakage of wastewater from wall boxes onto the floor, and that SPBs were not always disinfected and dried appropriately before reuse. Multiple deficiencies in hand hygiene and station disinfection were observed. No deficiencies in water treatment practices were identified, and water cultures were negative for the observed pathogens. CONCLUSIONS: The cluster of D acidovorans infections was most likely due to indirect exposures to contaminated wall boxes and possibly SPBs due to poor hand hygiene and station disinfection.

Weil's Disease in an HIV-Infected Patient.

Leptospirosis is a zoonosis caused by the spirochete Leptospira. Most cases of leptospirosis are mild to moderate and self-limited. The course of disease, however, may be complicated by multiorgan dysfunction with liver and kidney failure causing Weil's disease. Leptospirosis is also rare among HIV-infected patients. We report a case of an HIV-infected patient with Weil's disease.

Hepatitis B Virus Mutant Infections in Hemodialysis Patients: A Case Series.

RATIONALE & OBJECTIVE: Hepatitis B virus (HBV) transmission in hemodialysis units has become a rare event since implementation of hemodialysis-specific infection control guidelines: performing hemodialysis for hepatitis B surface antigen (HBsAg)-positive patients in an HBV isolation room, vaccinating HBV-susceptible (HBV surface antibody and HBsAg negative) patients, and monthly HBsAg testing in HBV-susceptible patients. Mutations in HBsAg can result in false-negative HBsAg results, leading to failure to identify HBsAg seroconversion from negative to positive. We describe 4 unique cases of HBsAg seroconversion caused by mutant HBV infection or reactivation in hemodialysis patients. STUDY DESIGN: Following identification of a possible HBsAg seroconversion and mutant HBV infection, public health investigations were launched to conduct further HBV testing of case patients and potentially exposed patients. A case patient was defined as a hemodialysis patient with suspected mutant HBV infection because of false-negative HBsAg testing results. Confirmed case patients had HBV DNA sequences demonstrating S-gene mutations. SETTING & PARTICIPANTS: Case patients and patients potentially exposed to the case patient in the respective hemodialysis units in multiple US states. RESULTS: 4 cases of mutant HBV infection in hemodialysis patients were identified; 3 cases were confirmed using molecular sequencing. Failure of some HBsAg testing platforms to detect HBV mutations led to delays in applying HBV isolation procedures. Testing of potentially exposed patients did not identify secondary transmissions. LIMITATIONS: Lack of access to information on past HBsAg testing platforms and results led to challenges in ascertaining when HBsAg seroconversion occurred and identifying and testing all potentially exposed patients. CONCLUSIONS: Mutant HBV infections should be suspected in patients who test HBsAg negative and concurrently test positive for HBV DNA at high levels. Dialysis providers should consider using HBsAg assays that can also detect mutant HBV strains for routine HBV testing.

National Healthcare Safety Network (NHSN) Dialysis Event Surveillance Report for 2014.

BACKGROUND AND OBJECTIVES: Persons receiving outpatient hemodialysis are at risk for bloodstream and vascular access infections. The Centers for Disease Control and Prevention conducts surveillance for these infections through the National Healthcare Safety Network. We summarize 2014 data submitted to National Healthcare Safety Network Dialysis Event Surveillance. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Dialysis facilities report three types of dialysis events (bloodstream infections; intravenous antimicrobial starts; and pus, redness, or increased swelling at the hemodialysis vascular access site). Denominator data consist of the number of hemodialysis outpatients treated at the facility during the first 2 working days of each month. We calculated dialysis event rates stratified by vascular access type (e.g., arteriovenous fistula, arteriovenous graft, or central venous catheter) and standardized infection ratios (comparing individual facility observed with predicted numbers of infections) for bloodstream infections. We described pathogens identified among bloodstream infections. RESULTS: A total of 6005 outpatient hemodialysis facilities reported dialysis event data for 2014 to the National Healthcare Safety Network. These facilities reported 160,971 dialysis events, including 29,516 bloodstream infections, 149,722 intravenous antimicrobial starts, and 38,310 pus, redness, or increased swelling at the hemodialysis vascular access site events; 22,576 (76.5%) bloodstream infections were considered vascular access related. Most bloodstream infections (63.0%) and access-related bloodstream infections (69.8%) occurred in patients with a central venous catheter. The rate of bloodstream infections per 100 patient-months was 0.64 (0.26 for arteriovenous fistula, 0.39 for arteriovenous graft, and 2.16 for central venous catheter). Other dialysis event rates were also highest among patients with a central venous catheter. Facility bloodstream infection standardized infection ratio distribution was positively skewed with a median of 0.84. Staphylococcus aureus was the most commonly isolated bloodstream infection pathogen (30.6%), and 39.5% of S. aureus isolates tested were resistant to methicillin. CONCLUSIONS: The 2014 National Healthcare Safety Network Dialysis Event data represent nearly all United States outpatient dialysis facilities. Rates of infection and other dialysis events were highest among patients with a central venous catheter compared with other vascular access types. Surveillance data can help define the epidemiology of important infections in this patient population.

Dialysis Event Surveillance Report: National Healthcare Safety Network data summary, January 2007 through April 2011.

A total of 24,092 adverse events in hemodialysis outpatients during January 2007 through April 2011 were reported to the National Healthcare Safety Network. Of 2,656 bloodstream infections, 67.3% were in patients with central venous catheters. For all events, rates associated with central venous catheters were higher than for other vascular access types.

A Large Outbreak of Hepatitis C Virus Infections in a Hemodialysis Clinic.

BACKGROUND In November and December 2012, 6 patients at a hemodialysis clinic were given a diagnosis of new hepatitis C virus (HCV) infection. OBJECTIVE To investigate the outbreak to identify risk factors for transmission. METHODS A case patient was defined as a patient who was HCV-antibody negative on clinic admission but subsequently was found to be HCV-antibody positive from January 1, 2008, through April 30, 2013. Patient charts were reviewed to identify and describe case patients. The hypervariable region 1 of HCV from infected patients was tested to assess viral genetic relatedness. Infection control practices were evaluated via observations. A forensic chemiluminescent agent was used to identify blood contamination on environmental surfaces after cleaning. RESULTS Eighteen case patients were identified at the clinic from January 1, 2008, through April 30, 2013, resulting in an estimated 16.7% attack rate. Analysis of HCV quasispecies identified 4 separate clusters of transmission involving 11 case patients. The case patients and previously infected patients in each cluster were treated in neighboring dialysis stations during the same shift, or at the same dialysis station on 2 consecutive shifts. Lapses in infection control were identified. Visible and invisible blood was identified on multiple surfaces at the clinic. CONCLUSIONS Epidemiologic and laboratory data confirmed transmission of HCV among numerous patients at the dialysis clinic over 6 years. Infection control breaches were likely responsible. This outbreak highlights the importance of rigorous adherence to recommended infection control practices in dialysis settings.

Completeness of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection Reporting From Outpatient Hemodialysis Facilities to the National Healthcare Safety Network, 2013.

Reports of bloodstream infections caused by methicillin-resistant Staphylococcus aureus among chronic hemodialysis patients to 2 Centers for Disease Control and Prevention surveillance systems (National Healthcare Safety Network Dialysis Event and Emerging Infections Program) were compared to evaluate completeness of reporting. Many methicillin-resistant S. aureus bloodstream infections identified in hospitals were not reported to National Healthcare Safety Network Dialysis Event.

Outbreak of Tsukamurella species bloodstream infection among patients at an oncology clinic, West Virginia, 2011-2012.

OBJECTIVE: To determine the source and identify control measures of an outbreak of Tsukamurella species bloodstream infections at an outpatient oncology facility. DESIGN: Epidemiologic investigation of the outbreak with a case-control study. METHODS: A case was an infection in which Tsukamurella species was isolated from a blood or catheter tip culture during the period January 2011 through June 2012 from a patient of the oncology clinic. Laboratory records of area hospitals and patient charts were reviewed. A case-control study was conducted among clinic patients to identify risk factors for Tsukamurella species bloodstream infection. Clinic staff were interviewed, and infection control practices were assessed. RESULTS: Fifteen cases of Tsukamurella (Tsukamurella pulmonis or Tsukamurella tyrosinosolvens) bloodstream infection were identified, all in patients with underlying malignancy and indwelling central lines. The median age of case patients was 68 years; 47% were male. The only significant risk factor for infection was receipt of saline flush from the clinic during the period September-October 2011 (P = .03), when the clinic had been preparing saline flush from a common-source bag of saline. Other infection control deficiencies that were identified at the clinic included suboptimal procedures for central line access and preparation of chemotherapy. CONCLUSION: Although multiple infection control lapses were identified, the outbreak was likely caused by improper preparation of saline flush syringes by the clinic. The outbreak demonstrates that bloodstream infections among oncology patients can result from improper infection control practices and highlights the critical need for increased attention to and oversight of infection control in outpatient oncology settings.

A polymicrobial outbreak of surgical site infections following cardiac surgery at a community hospital in Florida, 2011-2012.

We describe an outbreak of 22 sternal surgical site infections following cardiac surgery, including 4 Gordonia infections. Possible operation room environmental contamination and suboptimal infection control practices regarding scrub attire may have contributed to the outbreak.

Cough and cold medication adverse events after market withdrawal and labeling revision.

BACKGROUND: In October 2007, manufacturers voluntarily withdrew over-the-counter (OTC) infant cough and cold medications (CCMs) from the US market. A year later, manufacturers announced OTC CCM labeling would be revised to warn against OTC CCM use by children aged <4 years. We determined whether emergency department (ED) visits for CCM adverse drug events (ADEs) declined after these interventions. METHODS: We used National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance data from 2004 to 2011 to estimate the number of ED visits for CCM ADEs before and after each intervention. RESULTS: Among children aged <2 years, ED visits for CCM ADEs decreased from 4.1% of all ADE ED visits before the market withdrawal to 2.4% of all ADE visits afterward (difference in proportion: -1.7%, 95% confidence interval [CI]: -2.7% to -0.6%). Among children aged 2 to 3 years, ED visits for CCM ADEs decreased from 9.5% of all ADE ED visits before the labeling revision announcement to 6.5% of all ADE visits afterward (difference in proportion: -3.0%, 95% CI: -5.4% to -0.6%). Unsupervised ingestions accounted for 64.3% (95% CI: 51.1% to 77.5%) of CCM ADE ED visits involving children aged <2 years after the withdrawal and 88.8% (95% CI: 83.8% to 93.8%) of visits involving children aged 2 to 3 years after the labeling revision announcement. CONCLUSIONS: After a voluntary market withdrawal and labeling revision, ED visits for CCM ADEs declined among children aged <2 years and 2 to 3 years relative to ADE ED visits for all drugs. Interventions addressing unsupervised ingestions are needed to reduce CCM ADEs.

Molecular characterization of ambiguous mutations in HIV-1 polymerase gene: implications for monitoring HIV infection status and drug resistance.

Detection of recent HIV infections is a prerequisite for reliable estimations of transmitted HIV drug resistance (t-HIVDR) and incidence. However, accurately identifying recent HIV infection is challenging due partially to the limitations of current serological tests. Ambiguous nucleotides are newly emerged mutations in quasispecies, and accumulate by time of viral infection. We utilized ambiguous mutations to establish a measurement for detecting recent HIV infection and monitoring early HIVDR development. Ambiguous nucleotides were extracted from HIV-1 pol-gene sequences in the datasets of recent (HIVDR threshold surveys [HIVDR-TS] in 7 countries; n=416) and established infections (1 HIVDR monitoring survey at baseline; n=271). An ambiguous mutation index of 2.04×10(-3) nts/site was detected in HIV-1 recent infections which is equivalent to the HIV-1 substitution rate (2×10(-3) nts/site/year) reported before. However, significantly higher index (14.41×10(-3) nts/site) was revealed with established infections. Using this substitution rate, 75.2% subjects in HIVDR-TS with the exception of the Vietnam dataset and 3.3% those in HIVDR-baseline were classified as recent infection within one year. We also calculated mutation scores at amino acid level at HIVDR sites based on ambiguous or fitted mutations. The overall mutation scores caused by ambiguous mutations increased (0.54×10(-2)3.48×10(-2)/DR-site) whereas those caused by fitted mutations remained stable (7.50-7.89×10(-2)/DR-site) in both recent and established infections, indicating that t-HIVDR exists in drug-naïve populations regardless of infection status in which new HIVDR continues to emerge. Our findings suggest that characterization of ambiguous mutations in HIV may serve as an additional tool to differentiate recent from established infections and to monitor HIVDR emergence.