Sarah A. Clock

Contact precautions for multidrug-resistant organisms: Current recommendations and actual practice

BACKGROUND Contact precautions are recommended for interactions with patients colonized/infected with multidrug-resistant organisms; however, actual rates of implementation of contact precautions are unknown. METHODS Observers recorded the availability of supplies and staff/visitor adherence to contact precautions at rooms of patients indicated for contact precautions. Data were collected at 3 sites in a New York City hospital network. RESULTS Contact precautions signs were present for 85.4% of indicated patients. The largest proportions were indicated for isolation for vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus cultures. Isolation carts were available outside 93.7% to 96.7% of rooms displaying signs, and personal protective equipment was available at rates of 49.4% to 72.1% for gloves (all sizes: small, medium, and large) and 91.7% to 95.2% for gowns. Overall adherence rates on room entry and exit, respectively, were 19.4% and 48.4% for hand hygiene, 67.5% and 63.5% for gloves, and 67.9% and 77.1% for gowns. Adherence was significantly better in intensive care units (P < .05) and by patient care staff (P < .05), and patient care staff compliance with one contact precautions behavior was predictive of adherence to additional behaviors (P < .001). CONCLUSIONS Our findings support the recommendation that methods to monitor contact precautions and identify and correct nonadherent practices should be a standard component of infection prevention and control programs.

Outer membrane components of the Tad (tight adherence) secreton of Aggregatibacter actinomycetemcomitans.

Prokaryotic secretion relies on proteins that are widely conserved, including NTPases and secretins, and on proteins that are system specific. The Tad secretion system in Aggregatibacter actinomycetemcomitans is dedicated to the assembly and export of Flp pili, which are needed for tight adherence. Consistent with predictions that RcpA forms the multimeric outer membrane secretion channel (secretin) of the Flp pilus biogenesis apparatus, we observed the RcpA protein in multimers that were stable in the presence of detergent and found that rcpA and its closely related homologs form a novel and distinct subfamily within a well-supported gene phylogeny of the entire secretin gene superfamily. We also found that rcpA-like genes were always linked to Aggregatibacter rcpB- or Caulobacter cpaD-like genes. Using antisera, we determined the localization and gross abundances of conserved (RcpA and TadC) and unique (RcpB, RcpC, and TadD) Tad proteins. The three Rcp proteins (RcpA, RcpB, and RcpC) and TadD, a putative lipoprotein, localized to the bacterial outer membrane. RcpA, RcpC, and TadD were also found in the inner membrane, while TadC localized exclusively to the inner membrane. The RcpA secretin was necessary for wild-type abundances of RcpB and RcpC, and TadC was required for normal levels of all three Rcp proteins. TadC abundance defects were observed in rcpA and rcpC mutants. TadD production was essential for wild-type RcpA and RcpB abundances, and RcpA did not multimerize or localize to the outer membrane without the expression of TadD. These data indicate that membrane proteins TadC and TadD may influence the assembly, transport, and/or function of individual outer membrane Rcp proteins.

Comparison of Polymyxin B, Tigecycline, Cefepime, and Meropenem MICs for KPC-Producing Klebsiella pneumoniae by Broth Microdilution, Vitek 2, and Etest

ABSTRACT 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.

Colistin susceptibility testing: evaluation of reliability for cystic fibrosis isolates of Pseudomonas aeruginosa and Stenotrophomonas maltophilia

OBJECTIVES Antibiotic susceptibility methods that are commonly used to test bacterial isolates from patients with cystic fibrosis are of uncertain reliability for the polymyxins. To assess the reliability of four standard testing methods, this pilot study used a challenge set that included polymyxin-resistant isolates of Pseudomonas aeruginosa and Stenotrophomonas maltophilia. METHODS Twenty-five P. aeruginosa and 12 S. maltophilia isolates were tested for susceptibility to colistin (polymyxin E). Repeatability (concordance of replicates performed concurrently), reproducibility (concordance of replicates performed over time) and comparability (concordance of different methods) of agar dilution, broth microdilution, Etest and disc diffusion were assessed through the use of descriptive statistics and scatterplot analyses. RESULTS All four methods displayed excellent repeatability (overall concordance rate of 99%). However, analysis of reproducibility revealed substantially lower rates of concordance (74% for agar dilution, 84% for broth microdilution and Etest, and 91% for disc diffusion). In addition, comparability to agar dilution of the three other methods was generally poor, with overall rates of very major error ranging from 12% for broth microdilution to 18% for Etest and disc diffusion. CONCLUSIONS Compared with agar dilution, other susceptibility testing methods give high rates of apparent false polymyxin susceptibility for cystic fibrosis isolates of P. aeruginosa and S. maltophilia. Prospective study of the correlation between in vitro susceptibility and clinical response is needed to clarify whether these discrepancies reflect oversensitivity of the agar dilution method or insensitivity of the other methods.

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 health care-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 (odds ratio [OR], 1.55; P = .047) and exposure to amikacin (OR, 13.81; P < .001), levofloxacin (OR, 2.05; P = .005), or trimethoprim-sulfamethoxazole (OR, 3.42; P = .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 [HR], 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 1-year increase), liver disease (HR, 3.34), immunocompromised state (HR, 2.03), and hospitalization in a medical ICU (HR, 1.85) predicted mortality. CONCLUSION 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.

In vitro activity of doripenem alone and in multi-agent combinations against extensively drug-resistant Acinetobacter baumannii and Klebsiella pneumoniae

Carbapenems are increasingly needed to treat infections caused by drug-resistant gram-negative bacilli (GNB), but carbapenem resistance is increasing. We evaluated the activity of doripenem by broth microdilution against 96 extensively drug-resistant (XDR) Acinetobacter baumannii and Klebsiella pneumoniae isolates from patients with hospital-associated infections. All isolates were non-susceptible to doripenem, but ≥ 1 doripenem combination demonstrated synergy (fractional inhibitory concentration index: ≤ 0.5 for 2 agents, ≤ 0.75 for 3 agents) against 7 (15%) A. baumannii and 23 (48%) K. pneumoniae isolates; doripenem with rifampin and/or polymyxin B were most active. As doripenem has unique potential for use in prolonged infusions, suggested pharmacodynamic (PD) breakpoints range from 2-8 μg/mL; synergistic activity was found for higher proportions of XDR-GNB at higher PD breakpoints with doripenem with amikacin or with rifampin. The clinical utility of these observations requires further study, as treatment options for XDR-GNB infections are limited.

The product of tadZ, a new member of the parA/minD superfamily, localizes to a pole in Aggregatibacter actinomycetemcomitans

Aggregatibacter actinomycetemcomitans establishes a tenacious biofilm that is important for periodontal disease. The tad locus encodes the components for the secretion and biogenesis of Flp pili, which are necessary for the biofilm to form. TadZ is required, but its function has been elusive. We show that tadZ genes belong to the parA/minD superfamily of genes and that TadZ from A. actinomycetemcomitans (AaTadZ) forms a polar focus in the cell independent of any other tad locus protein. Mutations indicate that regions in AaTadZ are required for polar localization and biofilm formation. We show that AaTadZ dimerizes and that all TadZ proteins are predicted to have a Walker‐like A box. However, they all lack the conserved lysine at position 6 (K6) present in the canonical Walker‐like A box. When the alanine residue (A6) in the atypical Walker‐like A box of AaTadZ was converted to lysine, the mutant protein remained able to dimerize and localize, but it was unable to allow the formation of a biofilm. Another essential biofilm protein, the ATPase (AaTadA), also localizes to a pole. However, its correct localization depends on the presence of AaTadZ. We suggest that the TadZ proteins mediate polar localization of the Tad secretion apparatus.

Colonization With Antimicrobial-Resistant Gram-Negative Bacilli at Neonatal Intensive Care Unit Discharge

Background The epidemiology of the colonization of infants with antimicrobial-resistant Gram-negative bacilli (GNB) at discharge from the neonatal intensive care unit (NICU) is not well understood. Methods A multicenter study in which rectal surveillance samples for culture were obtained at NICU discharge from infants hospitalized ≥14 days was performed. Factors associated with colonization with GNB resistant to gentamicin, third/fourth-generation cephalosporin agents, or carbapenem agents were assessed by using a fixed-effects model. Results Of these infants, 9% (119 of 1320) were colonized with ≥1 antimicrobial-resistant GNB. Prolonged treatment (≥10 days) with meropenem or third/fourth-generation cephalosporin agents or treatment for ≥5 days with a β-lactam/β-lactamase combination agent were associated with an increased risk of colonization with GNB resistant to gentamicin. Surgery and ≥5 days of treatment with third/fourth-generation cephalosporin agents, a β-lactam/β-lactamase combination agent, or metronidazole were associated with an increased risk of colonization with GNB resistant to third/fourth-generation cephalosporin agents. Female sex and prolonged treatment (≥10 days) with meropenem were associated with colonization with GNB resistant to carbapenem agents. Conclusions Prolonged treatment with broad-spectrum antibiotics was associated with the colonization of infants with antimicrobial-resistant GNB within 7 days of NICU discharge. These findings suggest the potential for dissemination of resistant GNB from colonized infants to other NICUs, the community, or pediatric long-term care facilities. Antimicrobial stewardship efforts aimed at improving appropriate antibiotic use could have a beneficial effect on the emergence of antimicrobial-resistant GNB in the NICU population.

Documentation of Contact Precautions in an Electronic Health Record

Contact precautions are implemented to reduce transmission of multidrug-resistant organisms but may also increase hospital costs and patient complications. The goal of this study was to determine the prevalence of documentation of contact precautions (provider orders and nursing flowsheet documentation) in an electronic health record. Orders and nursing documentation were simultaneously present for only 42.3% of patient rooms with contact precaution signs, and 17.8% of rooms with signs had neither orders nor nursing documentation.

Multicenter Study of Hand Carriage of Potential Pathogens by Neonatal ICU Healthcare Personnel.

A multicenter surveillance study was performed to determine the rates of hand carriage of potential pathogens among healthcare personnel in four neonatal intensive care units. Staphylococcus aureus, enterococci, and gram-negative bacilli were recovered from 8%, 3%, and 2% of 1000 hand culture samples, respectively.