scholarly journals The Perfidious Effect of Topical Placebo: Calibration of Staphylococcus aureus Ventilator-Associated Pneumonia Incidence within Selective Digestive Decontamination Studies versus the Broader Evidence Base

2013 ◽  
Vol 57 (9) ◽  
pp. 4524-4531 ◽  
Author(s):  
James C. Hurley
Keyword(s):  
Staphylococcus Aureus ◽  
Observational Studies ◽  
Estimating Equation ◽  
Evidence Base ◽  
Selective Digestive Decontamination ◽  
Generalized Estimating Equation ◽  
Ventilator Associated Pneumonia ◽  
Control Groups ◽  
Content Type ◽  
The Mean

ABSTRACTAmong various methods for preventing ventilator-associated pneumonia (VAP), the evidence base for selective digestive decontamination (SDD) appears most compelling. However, the extent ofStaphylococcus aureusemergence with SDD use remains uncertain. Groups from 37 observational studies and component (control and intervention) groups from 58 studies of SDD and other methods of VAP prevention were sourced exclusively from 10 systematic reviews.S. aureusas a proportion of VAP isolates (S. aureusisolate proportion [S. aureusIP]) among component groups was calibrated versus that among observational groups (the benchmark). The influence of topical placebo used for blinding purposes and other group-level factors was estimated using generalized estimating equation methods (GEE). The meanS. aureusIP is 22% (95% confidence interval [CI], 19 to 25) for 37 observational groups versus 32% (24 to 41) and 20% (15 to 25) for 22 control groups from the SDD evidence base which did versus did not receive topical placebo, respectively. In GEE models including all 148 observational and component groups, membership of a control (P= 0.03) or intervention (P< 0.001) group of an SDD study that used topical placebo was associated with higherS. aureusIP, whereas, in contrast, membership of these groups was without effect onPseudomonas aeruginosa. Topical placebo is implicated as a vehicle for selective cross-infection withS. aureuswithin the specific context of the SDD evidence base. This effect of topical placebo is perfidious; it could contribute to the higher VAP incidence and inflate the apparent “effectiveness” of SDD. The SDD evidence base requires reappraisal.

scholarly journals Unusually High Incidences of Pseudomonas Bacteremias Within Topical Polymyxin–Based Decolonization Studies of Mechanically Ventilated Patients: Benchmarking the Literature

2018 ◽  
Vol 5 (11) ◽  
Author(s):  
James C Hurley
Keyword(s):  
Odds Ratio ◽  
Observational Studies ◽  
Prolonged Mechanical Ventilation ◽  
Estimating Equation ◽  
Generalized Estimating Equation ◽  
Control Groups ◽  
Intervention Component ◽  
Mechanically Ventilated ◽  
The Mean ◽  
Summary Odds Ratio

Abstract Background Topical polymyxin (PM)–based regimens to decolonize patients receiving prolonged mechanical ventilation (MV) have been widely studied. However, paradoxical bacteremia incidences remain unexplained. Methods The literature was searched for studies of topical PM–based regimens used to decontaminate MV patients reporting incidences of overall and Pseudomonas bacteremia data. In addition, observational groups without any intervention and trials of various interventions other than topical PM (non-PM studies) served to provide external benchmarks and additional points of reference, respectively. The bacteremia incidences were extracted from the control and intervention (component) groups of these studies and compared with metaregression using generalized estimating equation methods. Results The summary odds ratio derived from studies of topical PM–based interventions against overall bacteremia was 0.60 (95% confidence interval [CI], 0.53–0.69). Benchmark incidences per 100 MV patients for overall (mean, 8.9%; 95% CI, 6.9% to 10.9%) and Pseudomonas (mean, 0.7%; 95% CI, 0.5% to 1.1%) bacteremia were derived from 16 observational studies. By contrast, among 17 studies of topical PM, the mean incidences among control groups for overall (mean, 15.3%; 95% CI, 11.5% to 20.3%) and Pseudomonas (mean, 1.6%; 95% CI, 0.9% to 3.1%) bacteremia were both higher, whereas these incidences in the intervention groups for both topical PM and non-PM studies were in each case more similar to the respective benchmarks. These paradoxical incidences cannot readily be explained in metaregression models. Conclusions Paradoxically, despite an apparent prevention effect of topical PM–based methods against bacteremia overall, the incidences of Pseudomonas bacteremia within the component groups of these studies are unusually high vs literature-derived benchmarks.

scholarly journals Incidences ofPseudomonas aeruginosa-Associated Ventilator-Associated Pneumonia within Studies of Respiratory Tract Applications of Polymyxin: Testing the Stoutenbeek Concurrency Postulates

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
James C. Hurley
Keyword(s):  
Respiratory Tract ◽  
Estimating Equation ◽  
Ventilator Associated Pneumonia ◽  
Control Groups ◽  
Content Type ◽  
Mechanically Ventilated ◽  
Concurrent Control ◽  
Component Group ◽  
Funnel Plots ◽  
The Mean

ABSTRACTRegimens containing topical polymyxin appear highly effective at preventing ventilator-associated pneumonia (VAP) overall and, more so, VAP caused by Gram-negative bacteria. However, Stoutenbeek's postulates that VAP incidences within studies of topical antibiotics depend on the context of whether the component (control and intervention) groups of each study were concurrent versus nonconcurrent remain untested. The literature was searched for concurrent control (CC) versus nonconcurrent control (NCC) designed studies of respiratory tract applications of topical polymyxin to mechanically ventilated (MV) patients that reported incidences ofPseudomonas-associated ventilator-associated pneumonia (PsVAP). Studies of various interventions other than topical polymyxin (nonpolymyxin studies) served to provide additional points of reference. The PsVAP incidences within the component groups of all studies were benchmarked against groups from observational studies. This was undertaken by meta-regression using generalized estimating equation methods. Dot plots, caterpillar plots, and funnel plots enable visual benchmarking. The PsVAP benchmark (and 95% confidence interval [CI]) derived from 102 observational groups is 4.6% (4.0 to 5.3%). In contrast, the mean PsVAP within NCC polymyxin intervention groups (1.6%; CI, 1.0 to 4.5%) is lower than that of all other component group categories. The mean PsVAP within CC polymyxin control groups (9.9%; CI, 7.6 to 12.8%) is higher than that of all other component group categories. The PsVAP incidences of control and intervention groups of studies of respiratory tract applications of polymyxin are dependent on whether the groups were within a concurrent versus nonconcurrent study. Stoutenbeek's concurrency postulates are validated.

scholarly journals Ceftobiprole EfficacyIn Vitroagainst Panton-Valentine Leukocidin Production andIn Vivoagainst Community-Associated Methicillin-Resistant Staphylococcus aureus Osteomyelitis in Rabbits

2012 ◽  
Vol 56 (12) ◽  
pp. 6291-6297 ◽  
Author(s):  
Azzam Saleh-Mghir ◽  
Oana Dumitrescu ◽  
Aurélien Dinh ◽  
Yassine Boutrad ◽  
Laurent Massias ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
The Mean ◽  
Mrsa Strains ◽  
Time Kill ◽  
Panton Valentine Leukocidin ◽  
Valentine Leukocidin

ABSTRACTCommunity-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) can cause osteomyelitis with severe sepsis and/or local complications in which a Panton-Valentine leukocidin (PVL) role is suspected.In vitrosub-MIC antibiotic effects on growth and PVL production by 11 PVL+MRSA strains, including the major CA-MRSA clones (USA300, including the LAC strain; USA400; and USA1000), and 11 PVL+methicillin-susceptibleS. aureus(MSSA) strains were tested in microplate culture. Time-kill analyses with ceftobiprole at its MIC were also run with LAC. Efficacies of ceftobiprole (40 mg/kg of body weight subcutaneously [s.c.] four times a day [q.i.d.]) or vancomycin (60 mg/kg intramuscularly [i.m.] twice a day [b.i.d.]) alone or combined with rifampin (10 mg/kg b.i.d.) against rabbit CA-MRSA osteomyelitis, induced by tibial injection of 3.4 × 107CFU of LAC, were compared. Treatment, started 14 days postinoculation, lasted 14 days.In vitro, 6/11 strains cultured with sub-MICs of ceftobiprole produced 1.6- to 4.8-fold more PVL than did the controls, with no link to specific clones. Rifampin decreased PVL production by all tested strains. In time-kill analyses at the LAC MIC (0.75 mg/liter), PVL production rose transiently at 6 and 8 h and then declined 2-fold at 16 h, concomitant with a 2-log10-CFU-count decrease.In vivo, the mean log10CFU/g of bone for ceftobiprole (1.44 ± 0.40) was significantly lower than that for vancomycin (2.37 ± 1.22) (P= 0.034), with 7/10 versus 5/11 bones sterilized, respectively. Combination with rifampin enhanced ceftobiprole (1.16 ± 0.04 CFU/g of bone [P= 0.056], 11/11 sterile bones) and vancomycin (1.23 ± 0.06 CFU/g [P= 0.011], 11/11 sterile bones) efficacies. Ceftobiprole bactericidal activity and the rifampin anti-PVL effect could play a role in these findings, which should be of interest for treating CA-MRSA osteomyelitis.

scholarly journals ComparativeIn VivoEfficacies of Epithelial Lining Fluid Exposures of Tedizolid, Linezolid, and Vancomycin for Methicillin-Resistant Staphylococcus aureus in a Mouse Pneumonia Model

2012 ◽  
Vol 56 (5) ◽  
pp. 2342-2346 ◽  
Author(s):  
Pamela R. Tessier ◽  
Rebecca A. Keel ◽  
Mao Hagihara ◽  
Jared L. Crandon ◽  
David P. Nicolau
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bacterial Density ◽  
Epithelial Lining ◽  
Control Groups ◽  
Epithelial Lining Fluid ◽  
Methicillin Resistant ◽  
Content Type ◽  
Treatment Groups

ABSTRACTThe antibacterial efficacies of tedizolid phosphate (TZD), linezolid, and vancomycin regimens simulating human exposures at the infection site against methicillin-resistantStaphylococcus aureus(MRSA) were compared in anin vivomouse pneumonia model. Immunocompetent BALB/c mice were orally inoculated with one of three strains of MRSA and subsequently administered 20 mg/kg TZD every 24 hours (q24h), 120 mg/kg linezolid q12h, or 25 mg/kg vancomycin q12h over 24 h. These regimens produced epithelial lining fluid exposures comparable to human exposures observed following intravenous regimens of 200 mg TZD q24h, 600 mg linezolid q12h, and 1 g vancomycin q12h. The differences in CFU after 24 h of treatment were compared between control and treatment groups. Vehicle-dosed control groups increased in bacterial density an average of 1.1 logs. All treatments reduced the bacterial density at 24 h with an average of 1.2, 1.6, and 0.1 logs for TZD, linezolid, and vancomycin, respectively. The efficacy of TZD versus linezolid regimens against the three MRSA isolates was not statistically different (P> 0.05), although both treatments were significantly different from controls. In contrast, the vancomycin regimen was significantly different from TZD against one MRSA isolate and from linezolid against all isolates. The vancomycin regimen was less protective than either the TZD or linezolid regimens, with overall survival of 61.1% versus 94.7% or 89.5%, respectively. At human simulated exposures to epithelial lining fluid, vancomycin resulted in minimal reductions in bacterial counts and higher mortality compared to those of either TZD or linezolid. TZD and linezolid showed similar efficacies in this MRSA pneumonia model.

scholarly journals Prospective Investigation of Nasal Mupirocin, Hexachlorophene Body Wash, and Systemic Antibiotics for Prevention of Recurrent Community-Associated Methicillin-Resistant Staphylococcus aureus Infections

2011 ◽  
Vol 56 (2) ◽  
pp. 1084-1086 ◽  
Author(s):  
Loren G. Miller ◽  
Jennifer Tan ◽  
Samantha J. Eells ◽  
Esther Benitez ◽  
Allen B. Radner
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Skin Infections ◽  
Methicillin Resistant ◽  
Content Type ◽  
Nasal Mupirocin ◽  
The Mean ◽  
Systemic Antibiotics ◽  
Prospective Investigation

ABSTRACTRecurrent community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) skin infections are an increasingly common problem. However, there are no data on the efficacy of decolonization regimens. We prospectively evaluated 31 patients with recurrent CA-MRSA skin infections who received nasal mupirocin, topical hexachlorophene body wash, and an oral anti-MRSA antibiotic. The mean number of MRSA infections after the intervention decreased significantly from baseline (0.03 versus 0.84 infections/month,P= <0.0001). This regimen appears promising at preventing recurrent CA-MRSA infections.

scholarly journals Daptomycin versus Vancomycin in a Methicillin-Resistant Staphylococcus aureus Endophthalmitis Rabbit Model: Bactericidal Effect, Safety, and Ocular Pharmacokinetics

2012 ◽  
Vol 56 (5) ◽  
pp. 2485-2492 ◽  
Author(s):  
Sophie Lefèvre ◽  
Maher Saleh ◽  
Luc Marcellin ◽  
Audrey Subilia ◽  
Tristan Bourcier ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Rabbit Model ◽  
Bacterial Count ◽  
Ocular Inflammation ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Bactericidal Efficacy ◽  
The Mean

ABSTRACTStaphylococcus aureusis a frequent cause of acute endophthalmitis, and infection with this virulent bacterium is often associated with a poor visual outcome. In this study, we investigated the bactericidal efficacy and the safety of intravitreal daptomycin (DAP), a lipopeptide antibiotic with broad-spectrum activity against Gram-positive bacteria, compared with those of intravitreal vancomycin (VAN) in a methicillin-resistantS. aureusendophthalmitis rabbit model. The pharmacokinetics and pharmacodynamics of daptomycin in the infected eyes were also studied. Rabbits were randomly divided into three treatment groups (n= 8) and one untreated group (n= 4), to compare the effect of single intravitreal injections of 0.2 mg and 1 mg of daptomycin (DAP 0.2 and DAP 1 groups, respectively) with that of 1 mg of intravitreal vancomycin (VAN 1 group). Vitreal aspirates were regularly collected and grading of ocular inflammation was regularly performed until euthanasia on day 7. In the DAP 0.2 group, 62.5% of the eyes were sterilized and the mean bacterial count presented a reduction of 1 log unit. In the DAP 1 and VAN 1 groups, the infection was eradicated (100% and 87.5% of eyes sterilized, respectively), with a 4-log-unit reduction of the mean bacterial count. The bactericidal efficacy in the DAP 1 group was not inferior to that in the VAN 1 group and was superior to that of the other regimens in limiting the ocular inflammation and preserving the architecture of the ocular structures (P< 0.05). The elimination half-life (t1/2β) of daptomycin was independent of the administered dose (38.8 ± 16.5 h and 40.9 ± 6.7 h, respectively, for the DAP 0.2 and DAP 1 groups) and was significantly longer than thet1/2βof vancomycin (20.5 ± 2.0 h for the VAN 1 group) (P< 0.05). This antibiotic could therefore be considered for the treatment of intraocular infections caused by Gram-positive bacteria.

scholarly journals The Effect of Hollyhock (Althaea officinalis L) Leaf Compresses Combined With Warm and Cold Compress on Breast Engorgement in Lactating Women

2016 ◽  
Vol 22 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Shahla Khosravan ◽  
Hossein Mohammadzadeh-Moghadam ◽  
Fatemeh Mohammadzadeh ◽  
Samane Ajam Khames Fadafen ◽  
Malihe Gholami
Keyword(s):  
Significant Relationship ◽  
Intervention Group ◽  
Estimating Equation ◽  
Generalized Estimating Equation ◽  
Control Groups ◽  
Lactating Women ◽  
Significant Difference ◽  
Althaea Officinalis ◽  
And Control ◽  
Generalized Estimating

Breast engorgement affects lactation. The present study was conducted to determine the effect of hollyhock combined with warm and cold compresses on improving breast engorgement in lactating women. Participants included 40 women with breast engorgement divided into intervention and control groups, with participants in both groups being applied routine interventions and warm compress before nursing and a cold compress after nursing; however, the intervention group was also applied hollyhock compress. Both groups received these treatments 6 times during 2 days. The data collected were analyzed in SPSS-16 using a generalized estimating equation. According to the results, a significant difference was observed in the overall breast engorgement severity in the intervention group ( P < .001). The severity of breast engorgement was also found to have a significant relationship with time ( P < .001). According to the findings, hollyhock leaf compress combined with performing routine interventions for breast engorgement can improve breast engorgement.

scholarly journals Comparative Efficacies of Human Simulated Exposures of Tedizolid and Linezolid against Staphylococcus aureus in the Murine Thigh Infection Model

2012 ◽  
Vol 56 (8) ◽  
pp. 4403-4407 ◽  
Author(s):  
R. A. Keel ◽  
P. R. Tessier ◽  
J. L. Crandon ◽  
D. P. Nicolau
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Density ◽  
Infection Model ◽  
Immunocompetent Mouse ◽  
Time Curve ◽  
Free Concentration ◽  
Content Type ◽  
The Mean

ABSTRACTTedizolid (formally torezolid) is an expanded-spectrum oxazolidinone with enhancedin vitropotency against Gram-positive pathogens, including methicillin-susceptibleStaphylococcus aureus(MSSA) and methicillin-resistantS. aureus(MRSA). The efficacies of human simulated exposures of tedizolid and linezolid againstS. aureusin an immunocompetent mouse thigh model over 3 days were compared. Four strains of MRSA and one of MSSA with tedizolid and linezolid MICs ranging from 0.25 to 0.5 and from 2 to 4 μg/ml, respectively, were utilized. Tedizolid or linezolid was administered in a regimen simulating a human steady-state 24-h area under the free concentration-time curve of 200 mg every 24 h (Q24) or 600 mg Q12, respectively. Thighs were harvested after 4, 8, 12, 24, 36, 48, and 72 h, and efficacy was determined by the change in bacterial density. The mean bacterial density in control mice increased over the 3-day period. After 24 h of treatment, a reduction in bacterial density of ≥1 log CFU was observed for both the tedizolid and linezolid treatments. Antibacterial activity was enhanced for both agents with a reduction of ≥2.6 log CFU after 72 h of treatment. Any statistically significant differences (P≤ 0.05) in efficacy between the agents were transient and did not persist throughout the 72-h treatment period. The tedizolid and linezolid regimens demonstrated similarin vivoefficacies against theS. aureusisolates tested. Both agents were bacteriostatic at 24 h and bactericidal on the third day of treatment. These data support the clinical utility of tedizolid for skin and skin structure infections caused byS. aureus, as well as the bactericidal activity of the oxazolidinones after 3 days of treatment.

scholarly journals Treatment of experimental endocarditis due to methicillin-susceptible or methicillin-resistant Staphylococcus aureus with trimethoprim-sulfamethoxazole and antibiotics that inhibit cell wall synthesis.

1995 ◽  
Vol 39 (4) ◽  
pp. 953-957 ◽  
Author(s):  
M de Górgolas ◽  
P Avilés ◽  
C Verdejo ◽  
M L Fernández Guerrero
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Pneumocystis Carinii ◽  
Control Group ◽  
Cell Wall Synthesis ◽  
Control Groups ◽  
Methicillin Resistant ◽  
The Mean ◽  
High Concentrations ◽  
Overall Mortality

Using two strains of Staphylococcus aureus, one susceptible and one heterogeneously resistant to methicillin, for which MICs and MBCs of trimethoprim-sulfamethoxazole (TMP-SMX) were 0.06 and 0.06 micrograms/ml and 0.06 and 0.25 microgram/ml, respectively (concentrations are those of TMP), we studied the efficacies of TMP-SMX and cloxacillin, teicoplanin, and vancomycin for treatment of experimental staphylococcal endocarditis. Rabbits were treated with dosages of TMP-SMX selected to achieve concentrations in serum equivalent to that obtained in humans treated for Pneumocystis carinii pneumonia. The overall mortality rate of rabbits treated with TMP-SMX was 84% at day 3, not different from that of the control groups (P > 0.1). No sterile vegetations were observed to be present in control groups or in animals treated with TMP-SMX. However, 26, 60, and 75% of rabbits treated with teicoplanin, cloxacillin, and vancomycin, respectively, showed sterile vegetations. For methicillin-susceptible S. aureus (MSSA), the mean vegetation counts were not significantly different between the control group and the group treated with TMP-SMX (P > 0.1). For methicillin-resistant S. aureus (MRSA), treatment with TMP-SMX was more effective than no therapy, decreasing the number of organisms in vegetations (P < 0.01). For both strains, therapy with cloxacillin and therapy with teicoplanin or vancomycin were significantly more effective than therapy with TMP-SMX. Despite high concentrations of teicoplanin in serum which exceeded MBCs for staphylococci more than 50 times at the peak and 10 times at the trough, therapy with cloxacillin or vancomycin was superior to therapy with teicoplanin against both MSSA and MRSA. These data do not support the use of TMP-SMX in treatment of endocarditis and other severe staphylococcal infections with high bacterial counts.

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