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1.  Risk factors and Outcomes of Infections Caused by Extremely Drug-Resistant Gram-Negative Bacilli in Patients Hospitalized in Intensive Care Units 
Background
Extremely drug-resistant gram-negative bacilli (XDR-GNB) increasingly cause healthcare-associated infections (HAIs) in intensive care units (ICUs).
Methods
A matched case-control (1:2) study was conducted from February 2007 to January 2010 in 16 ICUs. Case and control subjects had HAIs caused by GNB susceptible to ≤1 antibiotic versus ≥2 antibiotics, respectively. Logistic and Cox proportional hazards regression assessed risk factors for HAIs and predictors of mortality, respectively.
Results
Overall, 103 case and 195 control subjects were enrolled. An immunocompromised state (OR=1.55, p=0.047) and exposure to amikacin (OR=13.81, p<0.001), levofloxacin (OR=2.05, p=0.005), or trimethoprim-sulfamethoxazole (OR=3.42, p=0.009) were factors associated with XDR-GNB HAIs. Multiple factors in both case and control subjects significantly predicted increased mortality at different time intervals after HAI diagnosis. At 7 days, liver disease (Hazard Ratio [HZ]=5.52), immunocompromised state (HR=3.41), and bloodstream infection (HR=2.55) predicted mortality; at 15 days, age (HR=1.02 per year increase), liver disease (HR=3.34), and immunocompromised state (HR 2.03) predicted mortality; and at 30 days, age (HR=1.02 per one year increase), liver disease (HR=3.34), immunocompromised state (HR=2.03), and hospitalization in a medical ICU (HR=1.85) predicted mortality.
Conclusions
HAIs caused by XDR-GNB were associated with potentially modifiable factors. Age, liver disease, and immunocompromised state, but not XDR-GNB HAIs, were associated with mortality.
doi:10.1016/j.ajic.2014.01.027
PMCID: PMC4083852  PMID: 24725516
2.  The Global Challenge of Carbapenem-Resistant Enterobacteriaceae in Transplant Recipients and Patients With Hematologic Malignancies 
We summarize the current knowledge of the epidemiology of carbapenem-resistant Enterobacteriaceae infections in transplant recipients and patients with hematologic malignancies, and provide recommendations for antimicrobial therapy and strategies to minimize this emerging threat in these vulnerable populations.
Carbapenem-resistant Enterobacteriaceae (CRE) are emerging global pathogens. The spread of CRE to transplant recipients and patients with hematologic malignancies has ominous implications. These patients rely on timely, active antibacterial therapy to combat gram-negative infections; however, recommended empirical regimens are not active against CRE. Approximately 3%–10% of solid organ transplant (SOT) recipients in CRE-endemic areas develop CRE infection, and the infection site correlates with the transplanted organ. Mortality rates associated with CRE infections approach 40% in SOT recipients and 65% in patients with hematologic malignancies. Given that the current antimicrobial armamentarium to combat CRE is extremely limited, a multifaceted approach that includes antimicrobial stewardship and active surveillance is needed to prevent CRE infections in immunocompromised hosts. Improving outcomes of established infections will require the use of risk factor–based prediction tools and molecular assays to more rapidly administer CRE-active therapy and the development of new antimicrobial agents with activity against CRE.
doi:10.1093/cid/ciu052
PMCID: PMC4038783  PMID: 24463280
carbapenem resistance; Enterobacteriaceae; immunocompromised hosts
3.  Circulating Clinical Strains of Human Parainfluenza Virus Reveal Viral Entry Requirements for In Vivo Infection 
Journal of Virology  2014;88(22):13495-13502.
ABSTRACT
Human parainfluenza viruses (HPIVs) cause widespread respiratory infections, with no vaccines or effective treatments. We show that the molecular determinants for HPIV3 growth in vitro are fundamentally different from those required in vivo and that these differences impact inhibitor susceptibility. HPIV infects its target cells by coordinated action of the hemagglutinin-neuraminidase receptor-binding protein (HN) and the fusion envelope glycoprotein (F), which together comprise the molecular fusion machinery; upon receptor engagement by HN, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. Peptides derived from key regions of F can potently inhibit HPIV infection at the entry stage, by interfering with the structural transition of F. We show that clinically circulating viruses have fusion machinery that is more stable and less readily activated than viruses adapted to growth in culture. Fusion machinery that is advantageous for growth in human airway epithelia and in vivo confers susceptibility to peptide fusion inhibitors in the host lung tissue or animal, but the same fusion inhibitors have no effect on viruses whose fusion glycoproteins are suited for growth in vitro. We propose that for potential clinical efficacy, antivirals should be evaluated using clinical isolates in natural host tissue rather than lab strains of virus in cultured cells. The unique susceptibility of clinical strains in human tissues reflects viral inhibition in vivo.
IMPORTANCE Acute respiratory infection is the leading cause of mortality in young children under 5 years of age, causing nearly 20% of childhood deaths worldwide each year. The paramyxoviruses, including human parainfluenza viruses (HPIVs), cause a large share of these illnesses. There are no vaccines or drugs for the HPIVs. Inhibiting entry of viruses into the human cell is a promising drug strategy that blocks the first step in infection. To develop antivirals that inhibit entry, it is critical to understand the first steps of infection. We found that clinical viruses isolated from patients have very different entry properties from those of the viruses generally studied in laboratories. The viral entry mechanism is less active and more sensitive to fusion inhibitory molecules. We propose that to interfere with viral infection, we test clinically circulating viruses in natural tissues, to develop antivirals against respiratory disease caused by HPIVs.
doi:10.1128/JVI.01965-14
PMCID: PMC4249073  PMID: 25210187
4.  Identification and Characterization of Linezolid-Resistant cfr-Positive Staphylococcus aureus USA300 Isolates from a New York City Medical Center 
Antimicrobial Agents and Chemotherapy  2014;58(11):6949-6952.
The cfr gene was identified in three linezolid-resistant USA300 methicillin-resistant Staphylococcus aureus (MRSA) isolates collected over a 3-day period at a New York City medical center in 2011 as part of a routine surveillance program. Each isolate possessed a plasmid containing a pSCFS3-like cfr gene environment. Transformation of the cfr-bearing plasmids into the S. aureus ATCC 29213 background recapitulated the expected Cfr antibiogram, including resistance to linezolid, tiamulin, clindamycin, and florfenicol and susceptibility to tedizolid.
doi:10.1128/AAC.03380-14
PMCID: PMC4249436  PMID: 25136008
5.  Current Concepts in Laboratory Testing to Guide Antimicrobial Therapy 
Mayo Clinic Proceedings  2012;87(3):290-308.
Antimicrobial susceptibility testing (AST) is indicated for pathogens contributing to an infectious process that warrants antimicrobial therapy if susceptibility to antimicrobials cannot be predicted reliably based on knowledge of their identity. Such tests are most frequently used when the etiologic agents are members of species capable of demonstrating resistance to commonly prescribed antibiotics. Some organisms have predictable susceptibility to antimicrobial agents (ie, Streptococcus pyogenes to penicillin), and empirical therapy for these organisms is typically used. Therefore, AST for such pathogens is seldom required or performed. In addition, AST is valuable in evaluating the activity of new and experimental compounds and investigating the epidemiology of antimicrobial resistant pathogens. Several laboratory methods are available to characterize the in vitro susceptibility of bacteria to antimicrobial agents. When the nature of the infection is unclear and the culture yields mixed growth or usual microbiota (wherein the isolates usually bear little relationship to the actual infectious process), AST is usually unnecessary and results may, in fact, be dangerously misleading. Phenotypic methods for detection of specific antimicrobial resistance mechanisms are increasingly being used to complement AST (ie, inducible clindamycin resistance among several gram-positive bacteria) and to provide clinicians with preliminary direction for antibiotic selection pending results generated from standardized AST (ie, β-lactamase tests). In addition, molecular methods are being developed and incorporated by microbiology laboratories into resistance detection algorithms for rapid, sensitive assessment of carriage states of epidemiologically and clinically important pathogens, often directly from clinical specimens (ie, presence of vancomycin-resistant enterococci in fecal specimens).
doi:10.1016/j.mayocp.2012.01.007
PMCID: PMC3496983  PMID: 22386185
6.  Increase in Pneumococcus Macrolide Resistance, United States 
Emerging Infectious Diseases  2009;15(8):1260-1264.
During year 6 of the study, the incidence rate rose from ≈30% to 35.3%.
During year 6 (2005–2006) of the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin surveillance study, 6,747 Streptococcus pneumoniae isolates were collected at 119 centers. The susceptibility of these isolates to macrolides was compared with data from previous years. Macrolide resistance increased significantly in year 6 (35.3%) from the stable rate of ≈30% for the previous 3 years (p<0.0001). Macrolide resistance increased in all regions of the United States and for all patient age groups. Rates were highest in the south and for children 0–2 years of age. Lower-level efflux [mef(A)]–mediated macrolide resistance decreased in prevalence to ≈50%, and highly resistant [erm(B) + mef(A)] strains increased to 25%. Telithromycin and levofloxacin susceptibility rates were >99% and >98%, respectively, irrespective of genotype. Pneumococcal macrolide resistance in the United States showed its first significant increase since 2000. High-level macrolide resistance is also increasing.
doi:10.3201/eid1508.081187
PMCID: PMC2815953  PMID: 19751588
Streptococcus pneumoniae; streptococci; macrolides; surveillance; PROTEKT US; respiratory infections; bacteria; antimicrobial resistance; United States; research
7.  Endocarditis Caused by Rhodotorula Infection 
Journal of Clinical Microbiology  2014;52(1):374-378.
Rhodotorula is an emerging opportunistic fungal pathogen that is rarely reported to cause endocarditis. We describe a case involving a patient who developed endocarditis due to Rhodotorula mucilaginosa and Staphylococcus epidermidis, proven by culture and histopathology. The case illustrates the unique diagnostic and therapeutic challenges relevant to Rhodotorula spp.
doi:10.1128/JCM.01950-13
PMCID: PMC3911467  PMID: 24197888
8.  Active Surveillance for Carbapenem-Resistant Enterobacteriaceae Using Stool Specimens Submitted for Testing for Clostridium difficile 
Active surveillance to identify asymptomatic carriers of carbapenem-resistant Enterobacteriaceae (CRE) is a recommended strategy for CRE control in healthcare facilities. Active surveillance using stool specimens tested for Clostridium difficile is a relatively low-cost strategy to detect CRE carriers. Further evaluation of this and other risk factor–based active surveillance strategies is warranted.
doi:10.1086/674391
PMCID: PMC3984911  PMID: 24334803
9.  Septic Shock Caused by Klebsiella pneumoniae Carbapenemase-Producing Enterobacter gergoviae in a Neutropenic Patient with Leukemia 
Journal of Clinical Microbiology  2013;51(8):2794-2796.
We present the first reported infection caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacter gergoviae. The patient had leukemia and neutropenia and died of septic shock from KPC-producing E. gergoviae bacteremia. The emergence of KPCs in additional species of Enterobacteriaceae is alarming and may disproportionately affect patients with hematologic malignancies.
doi:10.1128/JCM.00004-13
PMCID: PMC3719649  PMID: 23761145
11.  Salmonella Neck Abscess as an Opportunistic Infection in Diabetes Mellitus 
Salmonella neck infections represent an uncommon cause of focal salmonellosis. While the incidence of nontyphoid salmonellosis is estimated at over 2 million cases annually, extraintestinal manifestations account for less than 1% of cases. This paper describes two patients with Salmonella neck abscesses as the initial presentation of diabetes mellitus. The first patient was diagnosed as having Salmonella enterica serotype Enteritidis sternocleidomastoid pyomyositis and the second patient Salmonella enterica serotype Typhimurium parapharyngeal abscess. Both patients had elevated hemoglobin A1c levels and had not been previously diagnosed with diabetes mellitus. Salmonella spp. should be on the differential as a causative pathogen in patients presenting with neck abscesses and poorly controlled glucose levels. Diabetes may be a risk factor for salmonellosis due to decreased gastric acidity and prolonged gastric transit time. Prompt incision and drainage accompanied by antibiotics remains the treatment of choice for infected neck abscesses.
doi:10.1155/2013/708419
PMCID: PMC3835521  PMID: 24307959
12.  Multiplex Real-Time PCR for Detection of an Epidemic KPC-Producing Klebsiella pneumoniae ST258 Clone 
We describe a multiplex real-time PCR assay capable of identifying both the epidemic Klebsiella pneumoniae ST258 clone and blaKPC carbapenemase genes in a single reaction. The assay displayed excellent sensitivity (100%) and specificity (100%) for identification of ST258 clone and blaKPC in a collection of 75 K. pneumoniae isolates comprising 41 sequence types. Our results suggest that this assay is an effective tool for surveillance of this clone among carbapenem-resistant K. pneumoniae clinical isolates.
doi:10.1128/AAC.00316-12
PMCID: PMC3370784  PMID: 22450983
13.  Correction: Endemic Acinetobacter baumannii in a New York Hospital 
PLoS ONE  2012;7(10):10.1371/annotation/22d2ce95-f6c5-46fa-9e32-0d0fd21e20df.
doi:10.1371/annotation/22d2ce95-f6c5-46fa-9e32-0d0fd21e20df
PMCID: PMC3502304
14.  Extended Spectrum Beta-Lactamase-Producing Enterobacteriaceae in International Travelers and Non-Travelers in New York City 
PLoS ONE  2012;7(9):e45141.
Background
We performed this study 1) to determine the prevalence of community-associated extended spectrum beta-lactamase producing Enterobacteriaceae (ESBLPE) colonization and infection in New York City (NYC); 2) to determine the prevalence of newly-acquired ESBLPE during travel; 3) to look for similarilties in contemporaneous hospital-associated bloodstream ESBLPE and travel-associated ESBLPE.
Methods
Subjects were recruited from a travel medicine practice and consented to submit pre- and post-travel stools, which were assessed for the presence of ESBLPE. Pre-travel stools and stools submitted for culture were used to estimate the prevalence of community-associated ESBLPE. The prevalence of ESBLPE-associated urinary tract infections was calculated from available retrospective data. Hospital-associated ESBLPE were acquired from saved bloodstream isolates. All ESBLPE underwent multilocus sequence typing (MLST) and ESBL characterization.
Results
One of 60 (1.7%) pre- or non-travel associated stool was colonized with ESBLPE. Among community-associated urine specimens, 1.3% of Escherichia coli and 1.4% of Klebsiella pneumoniae were identified as ESBLPE. Seven of 28 travelers (25.0%) acquired a new ESBLPE during travel. No similarities were found between travel-associated ESBLPE and hospital-associated ESBLPE. A range of imported ESBL genes were found, including CTX-M-14 and CTX-15.
Conclusion
ESBL colonization and infection were relatively low during the study period in NYC. A signficant minority of travelers acquired new ESBLPE during travel.
doi:10.1371/journal.pone.0045141
PMCID: PMC3447858  PMID: 23028808
15.  Predicting Risk for Death from MRSA Bacteremia1 
Emerging Infectious Diseases  2012;18(7):1072-1080.
Methicillin-resistant Staphylococcus aureus (MRSA) in the bloodstream is often fatal. Vancomycin is the most frequently prescribed drug for treatment of MRSA infections with demonstrated efficacy. Recently, however, some MRSA infections have not been responding to vancomycin, even those caused by strains considered susceptible. To provide optimal treatment and avoid vancomycin resistance, therapy should be tailored, especially for patients at highest risk for death. But who are these patients? A study that looked back at medical records and 699 frozen isolates found that risk for death from MRSA infection was highest among certain populations, including the elderly, nursing home residents, patients with severe sepsis, and patients with liver or kidney disease. Risk for death was not affected by the type of MRSA strain (vancomycin susceptible, heteroresistant, or intermediate resistant). Risk was lower among those who had consulted an infectious disease specialist. Thus, when choosing treatment for patients with MRSA infection, it is crucial to look at patient risk factors, not just MRSA strain type. For those at high risk, consultation with an infectious disease specialist is recommended.
Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is often fatal. To determine predictors of risk for death, we conducted a retrospective cohort study. We examined 699 episodes of MRSA bacteremia involving 603 patients admitted to an academic medical center in New York City during 2002–2007. Data came from chart reviews, hospital databases, and recultured frozen MRSA specimens. Among the 699 episodes, 55 were caused by vancomycin–intermediate resistant S. aureus strains, 55 by heteroresistant vancomycin-intermediate S. aureus strains, and 589 by non–vancomycin-resistant strains; 190 (31.5%) patients died. We used regression risk analysis to quantify the association between clinical correlates and death. We found that older age, residence in a nursing home, severe bacteremia, and organ impairment were independently associated with increased risk for death; consultation with an infectious disease specialist was associated with lower risk for death; and MRSA strain types were not associated with risk for death.
doi:10.3201/eid1807.101371
PMCID: PMC3376787  PMID: 22709685
MRSA; bacteremia; heteroresistant Staphylococcus aureus; hVISA; vancomycin intermediate Staphylococcus aureus; VISA; mortality; death; bacteria; antimicrobial resistance
16.  Comparative Effectiveness of Aminoglycosides, Polymyxin B, and Tigecycline for Clearance of Carbapenem-Resistant Klebsiella pneumoniae from Urine ▿ 
Antimicrobial Agents and Chemotherapy  2011;55(12):5893-5899.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an increasingly common cause of health care-associated urinary tract infections. Antimicrobials with in vitro activity against CRKP are typically limited to polymyxins, tigecycline, and often, aminoglycosides. We conducted a retrospective cohort study of cases of CRKP bacteriuria at New York-Presbyterian Hospital from January 2005 through June 2010 to compare microbiologic clearance rates based on the use of polymyxin B, tigecycline, or an aminoglycoside. We constructed three active antimicrobial cohorts based on the active agent used and an untreated cohort of cases that did not receive antimicrobial therapy with Gram-negative activity. Microbiologic clearance was defined as having a follow-up urine culture that did not yield CRKP. Cases without an appropriate follow-up culture or that received multiple active agents or less than 3 days of the active agent were excluded. Eighty-seven cases were included in the active antimicrobial cohorts, and 69 were included in the untreated cohort. The microbiologic clearance rate was 88% in the aminoglycoside cohort (n = 41), compared to 64% in the polymyxin B (P = 0.02; n = 25), 43% in the tigecycline (P < 0.001; n = 21), and 36% in the untreated (P < 0.001; n = 69) cohorts. Using multivariate analysis, the odds of clearance were lower for the polymyxin B (odds ratio [OR], 0.10; P = 0.003), tigecycline (OR, 0.08; P = 0.001), and untreated (OR, 0.14; P = 0.003) cohorts than for the aminoglycoside cohort. Treatment with an aminoglycoside, when active in vitro, was associated with a significantly higher rate of microbiologic clearance of CRKP bacteriuria than treatment with either polymyxin B or tigecycline.
doi:10.1128/AAC.00387-11
PMCID: PMC3232750  PMID: 21968368
18.  Endemic Acinetobacter baumannii in a New York Hospital 
PLoS ONE  2011;6(12):e28566.
Background
Acinetobacter baumannii is an increasingly multidrug-resistant (MDR) cause of hospital-acquired infections, often associated with limited therapeutic options. We investigated A. baumannii isolates at a New York hospital to characterize genetic relatedness.
Methods
Thirty A. baumannii isolates from geographically-dispersed nursing units within the hospital were studied. Isolate relatedness was assessed by repetitive sequence polymerase chain reaction (rep-PCR). The presence and characteristics of integrons were assessed by PCR. Metabolomic profiles of a subset of a prevalent strain isolates and sporadic isolates were characterized and compared.
Results
We detected a hospital-wide group of closely related carbapenem resistant MDR A. baumannii isolates. Compared with sporadic isolates, the prevalent strain isolates were more likely to be MDR (p = 0.001). Isolates from the prevalent strain carried a novel Class I integron sequence. Metabolomic profiles of selected prevalent strain isolates and sporadic isolates were similar.
Conclusion
The A. baumannii population at our hospital represents a prevalent strain of related MDR isolates that contain a novel integron cassette. Prevalent strain and sporadic isolates did not segregate by metabolomic profiles. Further study of environmental, host, and bacterial factors associated with the persistence of prevalent endemic A. baumannii strains is needed to develop effective prevention strategies.
doi:10.1371/journal.pone.0028566
PMCID: PMC3236744  PMID: 22180786
19.  Comparison of Polymyxin B, Tigecycline, Cefepime, and Meropenem MICs for KPC-Producing Klebsiella pneumoniae by Broth Microdilution, Vitek 2, and Etest▿ 
Journal of Clinical Microbiology  2011;49(5):1795-1798.
We report MIC agreement and error rates between broth microdilution (BMD), Vitek 2, and Etest against 48 clinical KPC-producing Klebsiella pneumoniae isolates for polymyxin B, tigecycline, cefepime, and meropenem. Both commercial testing methods were useful for tigecycline testing; Etest provided a conservative estimate of polymyxin B susceptibility. We suggest that laboratories consider the supplemental use of reference BMD or Etest for cefepime and meropenem for susceptibility testing of KPC-producing K. pneumoniae, as Vitek 2 did not provide reliable results.
doi:10.1128/JCM.02534-10
PMCID: PMC3122677  PMID: 21367993
20.  Comparison of Meropenem MICs and Susceptibilities for Carbapenemase-Producing Klebsiella pneumoniae Isolates by Various Testing Methods▿  
Journal of Clinical Microbiology  2010;48(7):2402-2406.
We describe the levels of agreement between broth microdilution, Etest, Vitek 2, Sensititre, and MicroScan methods to accurately define the meropenem MIC and categorical interpretation of susceptibility against carbapenemase-producing Klebsiella pneumoniae (KPC). A total of 46 clinical K. pneumoniae isolates with KPC genotypes, all modified Hodge test and blaKPC positive, collected from two hospitals in NY were included. Results obtained by each method were compared with those from broth microdilution (the reference method), and agreement was assessed based on MICs and Clinical Laboratory Standards Institute (CLSI) interpretative criteria using 2010 susceptibility breakpoints. Based on broth microdilution, 0%, 2.2%, and 97.8% of the KPC isolates were classified as susceptible, intermediate, and resistant to meropenem, respectively. Results from MicroScan demonstrated the most agreement with those from broth microdilution, with 95.6% agreement based on the MIC and 2.2% classified as minor errors, and no major or very major errors. Etest demonstrated 82.6% agreement with broth microdilution MICs, a very major error rate of 2.2%, and a minor error rate of 2.2%. Vitek 2 MIC agreement was 30.4%, with a 23.9% very major error rate and a 39.1% minor error rate. Sensititre demonstrated MIC agreement for 26.1% of isolates, with a 3% very major error rate and a 26.1% minor error rate. Application of FDA breakpoints had little effect on minor error rates but increased very major error rates to 58.7% for Vitek 2 and Sensititre. Meropenem MIC results and categorical interpretations for carbapenemase-producing K. pneumoniae differ by methodology. Confirmation of testing results is encouraged when an accurate MIC is required for antibiotic dosing optimization.
doi:10.1128/JCM.00267-10
PMCID: PMC2897473  PMID: 20484603
21.  Characterization of blaKPC-containing Klebsiella pneumoniae isolates detected in different institutions in the Eastern USA 
Background
The emergence of blaKPC-containing Klebsiella pneumoniae (KPC-Kp) isolates is attracting significant attention. Outbreaks in the Eastern USA have created serious treatment and infection control problems. A comparative multi-institutional analysis of these strains has not yet been performed.
Methods
We analysed 42 KPC-Kp recovered during 2006–07 from five institutions located in the Eastern USA. Antimicrobial susceptibility tests, analytical isoelectric focusing (aIEF), PCR and sequencing of bla genes, PFGE and rep-PCR were performed.
Results
By in vitro testing, KPC-Kp isolates were highly resistant to all non-carbapenem β-lactams (MIC90s ≥ 128 mg/L). Among carbapenems, MIC50/90s were 4/64 mg/L for imipenem and meropenem, 4/32 mg/L for doripenem and 8/128 for ertapenem. Combinations of clavulanate or tazobactam with a carbapenem or cefepime did not significantly lower the MIC values. Genetic analysis revealed that the isolates possessed the following bla genes: blaKPC-2 (59.5%), blaKPC-3 (40.5%), blaTEM-1 (90.5%), blaSHV-11 (95.2%) and blaSHV-12 (50.0%). aIEF of crude β-lactamase extracts from these strains supported our findings, showing β-lactamases at pIs of 5.4, 7.6 and 8.2. The mean number of β-lactamases was 3.5 (range 3–5). PFGE demonstrated that 32 (76.2%) isolates were clonally related (type A). Type A KPC-Kp isolates (20 blaKPC-2 and 12 blaKPC-3) were detected in each of the five institutions. rep-PCR showed patterns consistent with PFGE.
Conclusions
We demonstrated the complex β-lactamase background of KPC-Kp isolates that are emerging in multiple centres in the Eastern USA. The prevalence of a single dominant clone suggests that interstate transmission has occurred.
doi:10.1093/jac/dkn547
PMCID: PMC2640158  PMID: 19155227
carbapenemases; ESBLs; Enterobacteriaceae; PFGE; rep-PCR
23.  Presence of Plasmid-Mediated Quinolone Resistance in Klebsiella pneumoniae Isolates Possessing blaKPC in the United States▿  
The presence of plasmid-mediated quinolone resistance genes [i.e., qnrA, qnrB, qnrS, aac(6′)-Ib-cr, and qepA] was evaluated among 42 blaKPC-containing Klebsiella pneumoniae isolates collected in the eastern United States. One isolate carried the blaKPC-3 and qnrB19 genes on the same conjugative plasmid, whereas another carried the blaKPC-3 and qnrA1 genes on separate plasmids.
doi:10.1128/AAC.00158-08
PMCID: PMC2443894  PMID: 18426899
24.  Trends in antibacterial resistance among Streptococcus pneumoniae isolated in the USA: update from PROTEKT US Years 1–4 
Background
The increasing prevalence of resistance to established antibiotics among key bacterial respiratory tract pathogens, such as Streptococcus pneumoniae, is a major healthcare problem in the USA. The PROTEKT US study is a longitudinal surveillance study designed to monitor the susceptibility of key respiratory tract pathogens in the USA to a range of commonly used antimicrobials. Here, we assess the geographic and temporal trends in antibacterial resistance of S. pneumoniae isolates from patients with community-acquired respiratory tract infections collected between Year 1 (2000–2001) and Year 4 (2003–2004) of PROTEKT US.
Methods
Antibacterial minimum inhibitory concentrations were determined centrally using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method; susceptibility was defined according to CLSI interpretive criteria. Macrolide resistance genotypes were determined by polymerase chain reaction.
Results
A total of 39,495 S. pneumoniae isolates were collected during 2000–2004. The percentage of isolates resistant to erythromycin, penicillin, levofloxacin, and telithromycin were 29.3%, 21.2%, 0.9%, and 0.02%, respectively, over the 4 years, with marked regional variability. The proportion of isolates exhibiting multidrug resistance (includes isolates known as penicillin-resistant S. pneumoniae and isolates resistant to ≥ 2 of the following antibiotics: penicillin; second-generation cephalosporins, e.g. cefuroxime; macrolides; tetracyclines; and trimethoprim-sulfamethoxazole) remained stable at ~30% over the study period. Overall mef(A) was the most common macrolide resistance mechanism. The proportion of mef(A) isolates decreased from 68.8% to 62.3% between Year 1 and Year 4, while the percentage of isolates carrying both erm(B) and mef(A) increased from 9.7% to 18.4%. Over 99% of the erm(B)+mef(A)-positive isolates collected over Years 1–4 exhibited multidrug resistance. Higher than previously reported levels of macrolide resistance were found for mef(A)-positive isolates.
Conclusion
Over the first 4 years of PROTEKT US, penicillin and erythromycin resistance among pneumococcal isolates has remained high. Although macrolide resistance rates have stabilized, the prevalence of clonal isolates, with a combined erm(B) and mef(A) genotype together with high-level macrolide and multidrug resistance, is increasing, and their spread may have serious health implications. Telithromycin and levofloxacin both showed potent in vitro activity against S. pneumoniae isolates irrespective of macrolide resistance genotype.
doi:10.1186/1476-0711-7-1
PMCID: PMC2262084  PMID: 18190701
25.  Prevalence and Antibacterial Susceptibility of mef(A)-Positive Macrolide-Resistant Streptococcus pneumoniae over 4 Years (2000 to 2004) of the PROTEKT US Study▿  
Journal of Clinical Microbiology  2006;45(2):290-293.
In the United States, approximately 30% of Streptococcus pneumoniae isolates are macrolide (erythromycin [ERY]) resistant (ERSP), most commonly due to expression of the mef(A) gene previously associated with lower-level ERY resistance (ERYr; MIC = 1 to 4 μg/ml). The data from the PROTEKT US surveillance study were analyzed to evaluate the prevalence and antibacterial susceptibility of mef(A)-positive ERSP. In all, 26,634 isolates of S. pneumoniae were collected in the United States between 2000 and 2004 from centers common to all years. ERYr was stable at approximately 29% over the 4 years, but the proportion of ERSP isolates positive for mef(A) alone decreased (year 1 [2000 to 2001], 69.0%; year 4 [2003 to 2004], 60.7%), with the sharpest declines seen in isolates from patients from 0 to 2 years of age. Conversely, the proportion isolates positive for both erm(B) and mef(A) increased over the duration of the present study (year 1, 9.3%; year 4, 19.1%), a change that was again most marked in patients aged ≤2 years. The majority of ERSP isolates expressing mef(A) alone exhibited higher than previously reported levels of ERYr (MIC90 = 16 μg/ml). However, the ketolide antibacterial telithromycin consistently demonstrated in vitro activity against these isolates over the 4 years of the study (MIC90 = 0.5 to 1 μg/ml).
doi:10.1128/JCM.01653-06
PMCID: PMC1829018  PMID: 17093012

Results 1-25 (27)