Steckelberg, James M.

ABSTRACT The activity of electrical current against planktonic bacteria has previously been demonstrated. The short-term exposure of the bacteria in biofilms to electrical current in the absence of antimicrobials has been shown to have no substantial effect; however, longer-term exposure has not been studied. A previously described in vitro model was used to determine the effect of prolonged exposure (i.e., up to 7 days) to low-intensity (i.e., 20-, 200-, and 2,000-microampere) electrical direct currents on Pseudomonas aeruginosa , Staphylococcus aureus , and Staphylococcus epidermidis biofilms. Dose- and time-dependent killing was observed. A maximum of a 6-log 10 -CFU/cm 2 reduction was observed when S. epidermidis biofilms were exposed to 2,000 microamperes for at least 2 days. A 4- to 5-log 10 -CFU/cm 2 reduction was observed when S. aureus biofilms were exposed to 2,000 microamperes for at least 2 days. Finally, a 3.5- to 5-log 10 -CFU/cm 2 reduction was observed when P. aeruginosa biofilms were exposed to electrical current for 7 days. A higher electrical current intensity correlated with greater decreases in viable bacteria at all time points studied. In conclusion, low-intensity electrical current substantially reduced the numbers of viable bacteria in staphylococcal or Pseudomonas biofilms, a phenomenon we have labeled the “electricidal effect.”

ABSTRACT Bacterial biofilms are resistant to conventional antimicrobial agents. Prior in vitro studies have shown that electrical current (EC) enhances the activities of aminoglycosides, quinolones, and oxytetracycline against Pseudomonas aeruginosa , Klebsiella pneumoniae , Staphylococcus epidermidis , Escherichia coli , and Streptococcus gordonii . This phenomenon, known as the bioelectric effect, has been only partially defined. The purpose of this work was to study the in vitro bioelectric effect on the activities of 11 antimicrobial agents representing a variety of different classes against P. aeruginosa , methicillin-resistant Staphylococcus aureus (MRSA), and S. epidermidis . An eight-channel current generator/controller and eight chambers delivering a continuous flow of fresh medium with or without antimicrobial agents and/or EC to biofilm-coated coupons were used. No significant decreases in the numbers of log 10 CFU/cm 2 were seen after exposure to antimicrobial agents alone, with the exception of a 4.57-log-unit reduction for S. epidermidis and trimethoprim-sulfamethoxazole. We detected a statistically significant bioelectric effect when vancomycin plus 2,000 microamperes EC were used against MRSA biofilms ( P = 0.04) and when daptomycin and erythromycin were used in combination with 200 or 2,000 microamperes EC against S. epidermidis biofilms ( P = 0.02 and 0.0004, respectively). The results of these experiments indicate that the enhancement of the activity of antimicrobial agents against biofilm organisms by EC is not a generalizable phenomenon across microorganisms and antimicrobial agents.

ABSTRACT We tested the activity of anidulafungin against 30 Candida albicans isolates. The planktonic MICs for 50 and 90% of the isolates tested (MIC 50 and MIC 90 ) were ≤0.03 and 0.125 μg/ml, respectively (MIC range, ≤0.03 to 2 μg/ml). The sessile MIC 50 and MIC 90 were ≤0.03 and ≤0.03 μg/ml, respectively (MIC range, ≤0.03 to >16 μg/ml).

Background— The role of valve surgery in left-sided infective endocarditis has not been evaluated in randomized controlled trials. We examined the association between valve surgery and all-cause 6-month mortality among patients with left-sided infective endocarditis. Methods and Results— A total of 546 consecutive patients with left-sided infective endocarditis were included. To minimize selection bias, propensity score to undergo valve surgery was used to match patients in the surgical and nonsurgical groups. To adjust for survivor bias, we matched the follow-up time so that each patient in the nonsurgical group survived at least as long as the time to surgery in the respective surgically-treated patient. We also used valve surgery as a time-dependent covariate in different Cox models. A total of 129 (23.6%) patients underwent surgery within 30 days of diagnosis. Death occurred in 99 of the 417 patients (23.7%) in the nonsurgical group versus 35 deaths among the 129 patients (27.1%) in the surgical group. Eighteen of 35 (51%) patients in the surgical group died within 7 days of valve surgery. In the subset of 186 cases (93 pairs of surgical versus nonsurgical cases) matched on the logit of their propensity score, diagnosis decade, and follow-up time, no significant association existed between surgery and mortality (adjusted hazard ratio, 1.3; 95% confidence interval, 0.5 to 3.1). With a Cox model that incorporated surgery as a time-dependent covariate, valve surgery was associated with an increase in the 6-month mortality with an adjusted hazard ratio of 1.9 (95% confidence interval, 1.1 to 3.2). Because the proportionality hazard assumption was violated in the time-dependent analysis, we performed a partitioning analysis. After adjustment for early (operative) mortality, surgery was not associated with a survival benefit (adjusted hazard ratio, 0.92; 95% confidence interval, 0.48 to 1.76). Conclusions— The results of our study suggest that valve surgery in left-sided infective endocarditis is not associated with a survival benefit and could be associated with increased 6-month mortality, even after adjustment for selection and survivor biases as well as confounders. Given the disparity between the results of our study and those of other observational studies, well-designed prospective studies are needed to further evaluate the role of valve surgery in endocarditis management.

ABSTRACT The activity of garenoxacin was compared to that of levofloxacin or penicillin in a rabbit model of Streptococcus mitis group (penicillin MIC, 0.125 μg/ml) and Streptococcus sanguinis group (penicillin MIC, 0.25 μg/ml) endocarditis. Garenoxacin and levofloxacin had MICs of 0.125 and 0.5 μg/ml, respectively, for both study isolates. Rabbits with catheter-induced aortic valve endocarditis were given no treatment, penicillin at 1.2 × 10 6 IU/8 h intramuscularly, garenoxacin at 20 mg/kg of body weight/12 h intravenously, or levofloxacin at 40 mg/kg/12 h intravenously. For both isolates tested, garenoxacin area under the curve (AUC)/MIC and maximum concentration of drug in serum ( C max )/MIC ratios were 368 and 91, respectively. Rabbits were sacrificed after 3 days of treatment; cardiac valve vegetations were aseptically removed and quantitatively cultured. For S. mitis group experimental endocarditis, all studied antimicrobial agents were more active than no treatment ( P < 0.001), whereas for S. sanguinis group endocarditis, no studied antimicrobial agents were more active than no treatment. We conclude that AUC/MIC and C max /MIC ratios may not predict activity of some quinolones in experimental viridans group endocarditis and that garenoxacin and levofloxacin may not be ideal choices for serious infections caused by some quinolone-susceptible viridans group streptococci.

ABSTRACT Explanted orthopedic implants from 54 patients with aseptic failure and 24 patients with prosthetic knee or hip infection were sonicated in polyethylene bags. The sensitivities of periprosthetic tissue and sonicate fluid cultures for the diagnosis of prosthetic joint infection were 54% and 75%, whereas the specificities were 98% and 87%, respectively. Sonication in bags improved bacterial recovery from the surface of orthopedic implants; however, it lacked specificity, due to bag leakage.

ABSTRACT Mupirocin MICs and mupA presence were determined in 108 staphylococci causing prosthetic joint infection. Zero of 35 isolates (0%) of methicillin-susceptible Staphylococcus aureus , 4/15 (27%) methicillin-resistant S. aureus isolates, 3/16 (19%) methicillin-susceptible coagulase-negative staphylococci, and 11/42 (26%) methicillin-resistant coagulase-negative staphylococci were mupirocin resistant. mupA was detected in all five high-level mupirocin-resistant staphylococci and one mupirocin-susceptible staphylococcus.

ABSTRACT Due to increasing mupirocin resistance, alternatives for Staphylococcus aureus nasal decolonization are needed. Lauric acid monoesters combined with lactic, mandelic, malic, or benzoic acid are being evaluated as possible alternatives. We determined the in vitro activity of 13 lauric acid monoester (LAM) formulations and mupirocin against 30 methicillin-susceptible S. aureus (MSSA) isolates and 30 methicillin-resistant S. aureus (MRSA) isolates. We then used a murine model of MRSA nasopharyngeal colonization to compare the in vivo activity of mupirocin with three LAM formulations. MSSA and MRSA MIC 90 values were 0.25 μg/ml for mupirocin and ≤4 μl/ml for all LAM formulations tested. Hsd:ICR mice were challenged with 10 8 CFU/naris MRSA. Five days later, S. aureus colonization was documented by culture. Treatment with bland, mupirocin, or one of three LAM ointments was then administered unblinded thrice daily for 2 days. Three days after treatment, both anterior nares were cultured for S. aureus . Administration of 128774-49E or 128774-53A was associated with greater eradication of MRSA carriage (24/34 [71%] or 33/40 [83%]) of animals, respectively) than bland ointment (12/38 [32%]) ( P < 0.005). 128774-53A administration resulted in greater MRSA carriage eradication than mupirocin (19/38 [50%]) ( P < 0.005) in this model. LAM formulations warrant evaluation for S. aureus nasal decolonization in humans.

ABSTRACT Exposure of ciprofloxacin- and cefepime-susceptible Pseudomonas aeruginosa isolates to increasing concentrations of ciprofloxacin selected for ciprofloxacin resistance in 26/27 and cefepime nonsusceptibility in 7/27 isolates. Exposure of the isolates to increasing concentrations of cefepime selected for cefepime nonsusceptibility in 20/27 isolates but not for ciprofloxacin resistance.