An observational prospective study of topical acidified nitrite for killing methicillin-resistant Staphylococcus aureus (MRSA) in contaminated wounds

Background Endogenous nitric oxide (NO) kills bacteria and other organisms as part of the innate immune response. When nitrite is exposed to low pH, NO is generated and has been used as an NO delivery system to treat skin infections. We demonstrated eradication of MRSA carriage from wounds using a topical formulation of citric acid (4.5%) and sodium nitrite (3%) creams co-applied for 5 days to 15 wounds in an observational prospective pilot study of 8 patients. Findings Following treatment with topical citric acid and sodium nitrite, 9 of 15 wounds (60%) and 3 of 8 patients (37%) were cleared of infection. MRSA isolates from these patients were all sensitive to acidified nitrite in vitro compared to methicillin-sensitive S. aureus and a reference strain of MRSA. Conclusions Nitric oxide and acidified nitrite offer a novel therapy for control of MRSA in wounds. Wounds that were not cleared of infection may have been re-contaminated or the bioavailability of acidified nitrite impaired by local factors in the tissue

Integration of molecular characterization of microorganisms in a global antimicrobial resistance surveillance program

© 2001 by the Infectious Diseases Society of America. All rights reserved.The SENTRY Antimicrobial Surveillance Program has incorporated molecular strain typing and resistance genotyping as a means of providing additional information that may be useful for understanding pathogenic microorganisms worldwide. Resistance phenotypes of interest include multidrug-resistant pathogens, extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, and fluoroquinolone-resistant (FQR) strains of gram-negative bacilli and Streptococcus pneumoniae. Clusters of 2 isolates within a given resistance profile that are linked temporally and by hospital location are flagged for DNA fingerprinting. Further characterization of organisms with respect to resistance genotype is accomplished with use of polymerase chain reaction and DNA sequencing. This process has been highly successful in identifying clonal spread within clusters of multiresistant pathogens. Between 50% and 90% of MRSA clusters identified by phenotypic screening contained evidence of clonal spread. Among the Enterobacteriaceae, ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae are the most common pathogens causing clusters of infection, and 50% of recognized clusters demonstrate clonal spread. Clusters of Pseudomonas aeruginosa, Acinetobacter species, and Stenotrophomonas maltophilia have been noted with clonal spread among patients with urinary tract, respiratory, and bloodstream infections. Characterization of mutations in the FQR-determining region of phenotypically susceptible isolates of E. coli and S. pneumoniae has identified first-stage mutants among as many as 40% of isolates. The ability to characterize organisms phenotypically and genotypically is extremely powerful and provides unique information that is important in a global antimicrobial surveillance program.M. A. Pfaller, J. Acar, R. N. Jones, J. Verhoef, J. Turnidge, and H. S. Sade

Pharmacy sales data versus ward stock accounting for the surveillance of broad-spectrum antibiotic use in hospitals

<p>Abstract</p> <p>Background</p> <p>Antibiotic consumption in hospitals is commonly measured using the accumulated amount of drugs delivered from the pharmacy to ward held stocks. The reliability of this method, particularly the impact of the length of the registration periods, has not been evaluated and such evaluation was aim of the study.</p> <p>Methods</p> <p>During 26 weeks, we performed a weekly ward stock count of use of broad-spectrum antibiotics <b>- </b>that is second- and third-generation cephalosporins, carbapenems, and quinolones <b>- </b>in five hospital wards and compared the data with corresponding pharmacy sales figures during the same period. Defined daily doses (DDDs) for antibiotics were used as measurement units (WHO ATC/DDD classification). Consumption figures obtained with the two methods for different registration intervals were compared by use of intraclass correlation analysis and Bland-Altman statistics.</p> <p>Results</p> <p>Broad-spectrum antibiotics accounted for a quarter to one-fifth of all systemic antibiotics (ATC group J01) used in the hospital and varied between wards, from 12.8 DDDs per 100 bed days in a urological ward to 24.5 DDDs in a pulmonary diseases ward. For the entire study period of 26 weeks, the pharmacy and ward defined daily doses figures for all broad-spectrum antibiotics differed only by 0.2%; however, for single wards deviations varied from -4.3% to 6.9%. The intraclass correlation coefficient, pharmacy versus ward data, increased from 0.78 to 0.94 for parenteral broad-spectrum antibiotics with increasing registration periods (1-4 weeks), whereas the corresponding figures for oral broad-spectrum antibiotics (ciprofloxacin) were from 0.46 to 0.74. For all broad-spectrum antibiotics and for parenteral antibiotics, limits of agreement between the two methods showed, according to Bland-Altman statistics, a deviation of ± 5% or less from average mean DDDs at 3- and 4-weeks registration intervals. Corresponding deviation for oral antibiotics was ± 21% at a 4-weeks interval.</p> <p>Conclusions</p> <p>There is a need for caution in interpreting pharmacy sales data aggregated over short registration intervals, especially so for oral formulations. Even a one-month registration period may be too short.</p

Pharmacological Investigations of the Dissociative ‘Legal Highs’ Diphenidine, Methoxphenidine and Analogues

1,2-Diarylethylamines including lanicemine, lefetamine, and remacemide have clinical relevance in a range of therapeutic areas including pain management, epilepsy, neurodegenerative disease and depression. More recently 1,2-diarylethylamines have been sold as ‘legal highs’ in a number of different forms including powders and tablets. These compounds are sold to circumvent governmental legislation regulating psychoactive drugs. Examples include the opioid MT-45 and the dissociative agents diphenidine (DPH) and 2-methoxy-diphenidine (2-MXP). A number of fatal and non-fatal overdoses have been linked to abuse of these compounds. As with many ‘legal highs’, little is known about their pharmacology. To obtain a better understanding, the effects of DPH, 2-MXP and its 3- and 4-MeO- isomers, and 2-Cl-diphenidine (2-Cl-DPH) were investigated using binding studies at 46 central nervous system receptors including the N-methyl-D-aspartate receptor (NMDAR), serotonin, dopamine, norepinephrine, histamine, and sigma receptors as well as the reuptake transporters for serotonin, dopamine and norepinephrine. Reuptake inhibition potencies were measured at serotonin, norepinephrine and dopamine transporters. NMDAR antagonism was established in vitro using NMDAR-induced field excitatory postsynaptic potential (fEPSP) experiments. Finally, DPH and 2-MXP were investigated using tests of pre-pulse inhibition of startle (PPI) in rats to determine whether they reduce sensorimotor gating, an effect observed with known dissociative drugs such as phencyclidine (PCP) and ketamine. The results suggest that these 1,2-diarylethylamines are relatively selective NMDAR antagonists with weak off-target inhibitory effects on dopamine and norepinephrine reuptake. DPH and 2-MXP significantly inhibited PPI. DPH showed greater potency than 2-MXP, acting with a median effective dose (ED50) of 9.5 mg/kg, which is less potent than values reported for other commonly abused dissociative drugs such as PCP and ketamine

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Quantifying antibiotic use in paediatrics: a proposal for neonatal DDDs

The defined daily dose (DDD) as defined by the World Health Organization (WHO) has been the most frequently used unit of measurement to measure antibiotic use. However, measuring antibiotic use in paediatrics is a problem as the WHO DDD methodology is not applicable in children (aged >1 month) due to the large variation in body weight within this population. Based on the narrow range of body weights in the neonatal population, we therefore aimed to develop a set of neonatal DDDs for antibiotics. Eight well-respected (inter)national sources for dosage recommendations of antibiotics in children and neonates were consulted for the assumed maintenance dose of the ten most frequently used antibiotics in neonatal intensive care units in its main indication for neonates. A set of neonatal DDDs for ten commonly used antibiotics in neonates based on an assumed neonatal weight of 2 kg was proposed. Primarily in children DDDs are not applicable to quantify antibiotic use since there is large variation in body weight. In the neonatal population, however, based on its narrow range of body weights and when access to patient level data is not available, neonatal DDDs can be used as a unit of measurement

Assessment of risk factors related to healthcare-associated methicillin-resistant Staphylococcus aureus infection at patient admission to an intensive care unit in Japan

<p>Abstract</p> <p>Background</p> <p>Healthcare-associated methicillin-resistant <it>Staphylococcus aureus </it>(HA-MRSA) infection in intensive care unit (ICU) patients prolongs ICU stay and causes high mortality. Predicting HA-MRSA infection on admission can strengthen precautions against MRSA transmission. This study aimed to clarify the risk factors for HA-MRSA infection in an ICU from data obtained within 24 hours of patient ICU admission.</p> <p>Methods</p> <p>We prospectively studied HA-MRSA infection in 474 consecutive patients admitted for more than 2 days to our medical, surgical, and trauma ICU in a tertiary referral hospital in Japan. Data obtained from patients within 24 hours of ICU admission on 11 prognostic variables possibly related to outcome were evaluated to predict infection risk in the early phase of ICU stay. Stepwise multivariate logistic regression analysis was used to identify independent risk factors for HA-MRSA infection.</p> <p>Results</p> <p>Thirty patients (6.3%) had MRSA infection, and 444 patients (93.7%) were infection-free. Intubation, existence of open wound, treatment with antibiotics, and steroid administration, all occurring within 24 hours of ICU admission, were detected as independent prognostic indicators. Patients with intubation or open wound comprised 96.7% of MRSA-infected patients but only 57.4% of all patients admitted.</p> <p>Conclusions</p> <p>Four prognostic variables were found to be risk factors for HA-MRSA infection in ICU: intubation, open wound, treatment with antibiotics, and steroid administration, all occurring within 24 hours of ICU admission. Preemptive infection control in patients with these risk factors might effectively decrease HA-MRSA infection.</p

Why do paediatricians prescribe antibiotics? Results of an Italian regional project

<p>Abstract</p> <p>Background</p> <p>To investigate determinants of antibiotic prescription in paediatric care, as a first step of a multilevel intervention to improve prescribing for common respiratory tract infections (RTIs) in a northern Italian region with high antibiotic prescription rate.</p> <p>Methods</p> <p>A two-step survey was performed: in phase I, knowledge, and attitudes were explored involving all family and hospital paediatricians of Emilia-Romagna and a sample of parents. In phase II, patient care practices were explored in a stratified random sample of visits, both in hospitals and family physician's clinics; parent expectations were investigated in a sub-sample of these visits.</p> <p>Results</p> <p>Out of overall 4352 visits for suspected RTIs, in 38% of children an antibiotic was prescribed. Diagnostic uncertainty was perceived by paediatricians as the most frequent cause of inappropriate prescription (56% of 633 interviewed paediatricians); but, rapid antigen detecting tests was used in case of pharyngitis/pharyngotonsillitis by 36% and 21% of family and hospital paediatricians only. More than 50% of paediatricians affirmed to not adopt a "wait and see strategy" in acute otitis. The perceived parental expectation of antibiotics was not indicated by paediatricians as a crucial determinant of prescription, but this perception was the second factor most strongly associated to prescription (OR = 12.8; 95% CI 10.4 - 15.8), the first being the presence of othorrea. Regarding parents, the most important identified factors, potentially associated to overprescribing, were the lack of knowledge of RTIs and antibiotics (41% of 1029 parents indicated bacteria as a possible cause of common cold), and the propensity to seek medical care for trivial infections (48% of 4352 children accessing ambulatory practice presented only symptoms of common cold).</p> <p>Conclusion</p> <p>A wide gap between perceived and real determinants of antibiotic prescription exists. This can promote antibiotic overuse. Inadequate parental knowledge can also induce inappropriate prescription. The value of this study is that it simultaneously explored determinants of antimicrobial prescribing in an entire region involving both professionals and parents.</p

Sequential introduction of single room isolation and hand hygiene campaign in the control of methicillin-resistant Staphylococcus aureus in intensive care unit

<p>Abstract</p> <p>Background</p> <p>After renovation of the adult intensive care unit (ICU) with installation of ten single rooms, an enhanced infection control program was conducted to control the spread of methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) in our hospital.</p> <p>Methods</p> <p>Since the ICU renovation, all patients colonized or infected with MRSA were nursed in single rooms with contact precautions. The incidence of MRSA infection in the ICU was monitored during 3 different phases: the baseline period (phase 1); after ICU renovation (phase 2) and after implementation of a hand hygiene campaign with alcohol-based hand rub (phase 3). Patients infected with extended spectrum beta-lactamase (ESBL)-producing <it>Escherichia coli </it>and <it>Klebsiella species </it>were chosen as controls because they were managed in open cubicles with standard precautions.</p> <p>Results</p> <p>Without a major change in bed occupancy rate, nursing workforce, or the protocol of environmental cleansing throughout the study period, a stepwise reduction in ICU onset nonbacteraemic MRSA infection was observed: from 3.54 (phase 1) to 2.26 (phase 2, p = 0.042) and 1.02 (phase 3, p = 0.006) per 1000-patient-days. ICU onset bacteraemic MRSA infection was significantly reduced from 1.94 (phase 1) to 0.9 (phase 2, p = 0.005) and 0.28 (phase 3, p = 0.021) per 1000-patient-days. Infection due to ESBL-producing organisms did not show a corresponding reduction. The usage density of broad-spectrum antibiotics and fluoroquinolones increased from phase 1 to 3. However a significant trend improvement of ICU onset MRSA infection by segmented regression analysis can only be demonstrated when comparison was made before and after the severe acute respiratory syndrome (SARS) epidemic. This suggests that the deaths of fellow healthcare workers from an occupational acquired infection had an overwhelming effect on their compliance with infection control measures.</p> <p>Conclusion</p> <p>Provision of single room isolation facilities and promotion of hand hygiene practice are important. However compliance with infection control measures relies largely on a personal commitment, which may increase when personal safety is threatened.</p