Antimicrobial Peptide Novicidin Synergizes with Rifampin, Ceftriaxone, and Ceftazidime against Antibiotic-Resistant Enterobacteriaceae In Vitro

The spread of antibiotic resistance among Gram-negative bacteria is a serious clinical threat, and infections with these organisms are a leading cause of mortality worldwide. Traditional novel drug development inevitably leads to the emergence of new resistant strains, rendering the new drugs ineffective. Therefore, reviving the therapeutic potentials of existing antibiotics represents an attractive novel strategy. Novicidin, a novel cationic antimicrobial peptide, is effective against Gram-negative bacteria. Here, we investigated novicidin as a possible antibiotic enhancer. The actions of novicidin in combination with rifampin, ceftriaxone, or ceftazidime were investigated against 94 antibiotic-resistant clinical Gram-negative isolates and 7 strains expressing New Delhi metallo-β-lactamase-1. Using the checkerboard method, novicidin combined with rifampin showed synergy with >70% of the strains, reducing the MICs significantly. The combination of novicidin with ceftriaxone or ceftazidime was synergistic against 89.7% of the ceftriaxone-resistant strains and 94.1% of the ceftazidime-resistant strains. Synergistic interactions were confirmed using time-kill studies with multiple strains. Furthermore, novicidin increased the postantibiotic effect when combined with rifampin or ceftriaxone. Membrane depolarization assays revealed that novicidin alters the cytoplasmic membrane potential of Gram-negative bacteria. In vitro toxicology tests showed novicidin to have low hemolytic activity and no detrimental effect on cell cultures. We demonstrated that novicidin strongly rejuvenates the therapeutic potencies of ceftriaxone or ceftazidime against resistant Gram-negative bacteria in vitro. In addition, novicidin boosted the activity of rifampin. This strategy can have major clinical implications in our fight against antibiotic-resistant bacterial infections

Attempts to eradicate methicillin-resistant Staphylococcus aureus from a long-term-care facility with the use of mupirocin ointment

: To assess the impact of the use of mupirocin ointment on colonization, transmission, and infection with methicillin-resistant Staphylococcus aureus (MRSA) in a long-termcare facility.: All 321 residents of a Veterans Affairs long-term-care facility from June 1990 through June 1991 were studied for MRSA colonization and infection. MRSA-colonized patients received mupirocin ointment to nares in the first 7 months and to nares and wounds in the second 5 months. The effect of mupirocin use on MRSA colonization and infection was monitored. All S. aureus strains isolated were tested for the development of resistance to mupirocin.: A total of 65 patients colonized with MRSA received mupirocin ointment. Mupirocin rapidly eliminated MRSA at the sites treated in most patients by the end of 1 week. Weekly maintenance mupirocin was not adequate to prevent recurrences--40% of patients had recurrence of MRSA. Overall, MRSA colonization in the facility, which was 22.7% +/- 1% prior to the use of mupirocin, did not change when mupirocin was used in nares only (22.2% +/- 2.1%), but did decrease to 11.5% +/- 1.8% when mupirocin was used in nares and wounds. Although colonization decreased, roommate-to-roommate transmission and MRSA infection rates, low to begin with, did not change when mupirocin was used. Mupirocin-resistant MRSA strains were isolated in 10.8% of patients.: Mupirocin ointment is effective at decreasing colonization with MRSA. However, constant surveillance was required to identify patients colonized at admission or experiencing recurrence of MRSA during maintenance treatment. Long-term use of mupirocin selected for mupirocin-resistant MRSA strahis. Mupirocin should be saved for use in outbreak situations, and not used over the long term in facilities with endemic MRSA colonization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30882/1/0000548.pd

Antimicrobial Drug Use and Methicillin-resistant Staphylococcus aureus, Aberdeen, 1996–2000

Relationships between antimicrobial use and MRSA prevalence are analyzed in Aberdeen, Scotland

Methicillin-resistant Staphylococcus aureus (MRSA) in rehabilitation and chronic-care-facilities: what is the best strategy?

BACKGROUND: The risk associated with methicillin-resistant Staphylococcus aureus (MRSA) has been decreasing for several years in intensive care departments, but is now increasing in rehabilitation and chronic-care-facilities (R-CCF). The aim of this study was to use published data and our own experience to discuss the roles of screening for MRSA carriers, the type of isolation to be implemented and the efficiency of chemical decolonization. DISCUSSION: Screening identifies over 90% of patients colonised with MRSA upon admission to R-CCF versus only 50% for intensive care units. Only totally dependent patients acquire MRSA. Thus, strict geographical isolation, as opposed to "social reinsertion", is clearly of no value. However, this should not lead to the abandoning of isolation, which remains essential during the administration of care. The use of chemicals to decolonize the nose and healthy skin appeared to be of some value and the application of this procedure could make technical isolation unnecessary in a non-negligible proportion of cases. SUMMARY: Given the increase in morbidity associated with MRSA observed in numerous hospitals, the emergence of a community-acquired disease associated with these strains and the evolution of glycopeptide-resistant strains, the voluntary application of a strategy combining screening, technical isolation and chemical decolonization in R-CCF appears to be an urgent matter of priority

PRImary care Streptococcal Management (PRISM) study:In vitro study, diagnostic cohorts and a pragmatic adaptive randomised controlled trial with nested qualitative study and cost-effectiveness study

Background: Antibiotics are still prescribed to most patients attending primary care with acute sore throat, despite evidence that there is modest benefit overall from antibiotics. Targeting antibiotics using either clinical scoring methods or rapid antigen detection tests (RADTs) could help. However, there is debate about which groups of streptococci are important (particularly Lancefield groups C and G), and uncertainty about the variables that most clearly predict the presence of streptococci. Objective: This study aimed to compare clinical scores or RADTs with delayed antibiotic prescribing. Design: The study comprised a RADT in vitro study; two diagnostic cohorts to develop streptococcal scores (score 1; score 2); and, finally, an open pragmatic randomised controlled trial with nested qualitative and cost-effectiveness studies. Setting: The setting was UK primary care general practices. Participants: Participants were patients aged ≥ 3 years with acute sore throat. Interventions: An internet program randomised patients to targeted antibiotic use according to (1) delayed antibiotics (control group), (2) clinical score or (3) RADT used according to clinical score. Main outcome measures: The main outcome measures were self-reported antibiotic use and symptom duration and severity on seven-point Likert scales (primary outcome: mean sore throat/difficulty swallowing score in the first 2-4 days). Results: The IMI TestPack Plus Strep A (Inverness Medical, Bedford, UK) was sensitive, specific and easy to use. Lancefield group A/C/G streptococci were found in 40% of cohort 2 and 34% of cohort 1. A five-point score predicting the presence of A/C/G streptococci [FeverPAIN: Fever; Purulence; Attend rapidly (≤ 3 days); severe Inflammation; and No cough or coryza] had moderate predictive value (bootstrapped estimates of area under receiver operating characteristic curve: 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection. In total, 38% of cohort 1 and 36% of cohort 2 scored ≤ 1 for FeverPAIN, associated with streptococcal percentages of 13% and 18%, respectively. In an adaptive trial design, the preliminary score (score 1; n = 1129) was replaced by FeverPAIN (n = 631). For score 1, there were no significant differences between groups. For FeverPAIN, symptom severity was documented in 80% of patients, and was lower in the clinical score group than in the delayed prescribing group (-0.33; 95% confidence interval -0.64 to -0.02; p = 0.039; equivalent to one in three rating sore throat a slight rather than moderately bad problem), and a similar reduction was observed for the RADT group (-0.30; -0.61 to 0.00; p = 0.053). Moderately bad or worse symptoms resolved significantly faster (30%) in the clinical score group (hazard ratio 1.30; 1.03 to 1.63) but not the RADT group (1.11; 0.88 to 1.40). In the delayed group, 75/164 (46%) used antibiotics, and 29% fewer used antibiotics in the clinical score group (risk ratio 0.71; 0.50 to 0.95; p = 0.018) and 27% fewer in the RADT group (0.73; 0.52 to 0.98; p = 0.033). No significant differences in complications or reconsultations were found. The clinical score group dominated both other groups for both the cost/quality-adjusted life-years and cost/change in symptom severity analyses, being both less costly and more effective, and cost-effectiveness acceptability curves indicated the clinical score to be the most likely to be cost-effective from an NHS perspective. Patients were positive about RADTs. Health professionals' concerns about test validity, the time the test took and medicalising self-limiting illness lessened after using the tests. For both RADTs and clinical scores, there were tensions with established clinical experience. Conclusions: Targeting antibiotics using a clinical score (FeverPAIN) efficiently improves symptoms and reduces antibiotic use. RADTs used in combination with FeverPAIN provide no clear advantages over FeverPAIN alone, and RADTs are unlikely to be incorporated into practice until health professionals' concerns are met and they have experience of using them. Clinical scores also face barriers related to clinicians' perceptions of their utility in the face of experience. This study has demonstrated the limitation of using one data set to develop a clinical score. FeverPAIN, derived from two data sets, appears to be valid and its use improves outcomes, but diagnostic studies to confirm the validity of FeverPAIN in other data sets and settings are needed. Experienced clinicians need to identify barriers to the use of clinical scoring methods. Implementation studies that address perceived barriers in the use of FeverPAIN are needed

Prospective Study of Infection, Colonization and Carriage of Methicillin-Resistant Staphylococcus Aureus in an Outbreak Affecting 990 Patients

In the three years between November 1989 and October 1992, an outbreak of methicillin-resistantStaphylococcus aureus (MRSA) affected 990 patients at a university hospital. The distribution of patients with carriage, colonization or infection was investigated prospectively. Nosocomial acquisition was confirmed in at least 928 patients, 525 of whom were identified from clinical specimens as being infected (n=418) or colonized (n=107) by MRSA. An additional 403 patients were identified from screening specimens, of whom 58 subsequently became infected and 18 colonized. Screening of the nose, throat and perineum detected 98 % of all carriers. Of the 580 infections in 476 patients, surgical wound, urinary tract and skin infections accounted for 58 % of the infections. Of the 476 infected patients, death was attributable to MRSA infection in 13 %. Colonization with MRSA was found in 127 patients and 42 % of 165 colonized sites were the skin. Auto-infection from nasal carriage or cross-infection, probably via staff hands, seemed to be the most common mode of acquisition of MRSA infections