Nasal decolonization of Staphylococcus aureus with mupirocin: strengths, weaknesses and future prospects

Staphylococcus aureus in the nose is a risk factor for endogenous staphylococcal infection. UK guidelines recommend the use of mupirocin for nasal decolonization in certain groups of patients colonized with methicillin-resistant S. aureus (MRSA). Mupirocin is effective at removing S. aureus from the nose over a few weeks, but relapses are common within several months. There are only a few prospective randomized clinical trials that have been completed with sufficient patients, but those that have been reported suggest that clearance of S. aureus from the nose is beneficial in some patient groups for the reduction in the incidence of nosocomial infections. There is no convincing evidence that mupirocin treatment reduces the incidence of surgical site infection. New antibiotics are needed to decolonize the nose because bacterial resistance to mupirocin is rising, and so it will become less effective. Furthermore, a more bactericidal antibiotic than mupirocin is needed, on the grounds that it might reduce the relapse rate, and so clear the patient of MRSA for a longer period of time than mupirocin

Bacterial infections in neonates following mupirocin-based MRSA decolonization: A multicenter cohort study

OBJECTIVETo characterize the risk of infection after MRSA decolonization with intranasal mupirocin.DESIGNMulticenter, retrospective cohort study.SETTINGTertiary care neonatal intensive care units (NICUs) from 3 urban hospitals in the United States ranging in size from 45 to 100 beds.METHODSMRSA-colonized neonates were identified from NICU admissions occurring from January 2007 to December 2014, during which a targeted decolonization strategy was used for MRSA control. In 2 time-to-event analyses, MRSA-colonized neonates were observed from the date of the first MRSA-positive surveillance screen until (1) the first occurrence of novel gram-positive cocci in sterile culture or discharge or (2) the first occurrence of novel gram-negative bacilli in sterile culture or discharge. Mupirocin exposure was treated as time varying.RESULTSA total of 522 MRSA-colonized neonates were identified from 16,144 neonates admitted to site NICUs. Of the MRSA-colonized neonates, 384 (74%) received mupirocin. Average time from positive culture to mupirocin treatment was 3.5 days (standard deviation, 7.2 days). The adjusted hazard of gram-positive cocci infection was 64% lower among mupirocin-exposed versus mupirocin-unexposed neonates (hazard ratio, 0.36; 95% confidence interval [CI], 0.17–0.76), whereas the adjusted hazard ratio of gram-negative bacilli infection comparing mupirocin-exposed and -unexposed neonates was 1.05 (95% CI, 0.42–2.62).CONCLUSIONSIn this multicentered cohort of MRSA-colonized neonates, mupirocin-based decolonization treatment appeared to decrease the risk of infection with select gram-positive organisms as intended, and the treatment was not significantly associated with risk of subsequent infections with organisms not covered by mupirocin’s spectrum of activity.Infect Control Hosp Epidemiol2017;38:930–936</jats:sec

A Natural Plasmid Uniquely Encodes Two Biosynthetic Pathways Creating a Potent Anti-MRSA Antibiotic

Background Understanding how complex antibiotics are synthesised by their producer bacteria is essential for creation of new families of bioactive compounds. Thiomarinols, produced by marine bacteria belonging to the genus Pseudoalteromonas, are hybrids of two independently active species: the pseudomonic acid mixture, mupirocin, which is used clinically against MRSA, and the pyrrothine core of holomycin. Methodology/Principal Findings High throughput DNA sequencing of the complete genome of the producer bacterium revealed a novel 97 kb plasmid, pTML1, consisting almost entirely of two distinct gene clusters. Targeted gene knockouts confirmed the role of these clusters in biosynthesis of the two separate components, pseudomonic acid and the pyrrothine, and identified a putative amide synthetase that joins them together. Feeding mupirocin to a mutant unable to make the endogenous pseudomonic acid created a novel hybrid with the pyrrothine via “mutasynthesis” that allows inhibition of mupirocin-resistant isoleucyl-tRNA synthetase, the mupirocin target. A mutant defective in pyrrothine biosynthesis was also able to incorporate alternative amine substrates. Conclusions/Significance Plasmid pTML1 provides a paradigm for combining independent antibiotic biosynthetic pathways or using mutasynthesis to develop a new family of hybrid derivatives that may extend the effective use of mupirocin against MRSA

Prevalence of qacA/B genes and mupirocin resistance among methicillin-resistant Staphylococcus aureus (MRSA) isolates in the setting of chlorhexidine bathing without mupirocin

OBJECTIVE: We aimed to determine the frequency of qacA/B chlorhexidine tolerance genes and high-level mupirocin resistance among MRSA isolates before and after the introduction of a chlorhexidine (CHG) daily bathing intervention in a surgical intensive care unit (SICU). DESIGN: Retrospective cohort study (2005–2012) SETTING: A large tertiary-care center PATIENTS: Patients admitted to SICU who had MRSA surveillance cultures of the anterior nares METHODS: A random sample of banked MRSA anterior nares isolates recovered during (2005) and after (2006–2012) implementation of a daily CHG bathing protocol was examined for qacA/B genes and high-level mupirocin resistance. Staphylococcal cassette chromosome mec (SCCmec) typing was also performed. RESULTS: Of the 504 randomly selected isolates (63 per year), 36 (7.1%) were qacA/B positive ( + ) and 35 (6.9%) were mupirocin resistant. Of these, 184 (36.5%) isolates were SCCmec type IV. There was a significant trend for increasing qacA/B (P= .02; highest prevalence, 16.9% in 2009 and 2010) and SCCmec type IV (P< .001; highest prevalence, 52.4% in 2012) during the study period. qacA/B( + ) MRSA isolates were more likely to be mupirocin resistant (9 of 36 [25%] qacA/B( + ) vs 26 of 468 [5.6%] qacA/B(−); P= .003). CONCLUSIONS: A long-term, daily CHG bathing protocol was associated with a change in the frequency of qacA/B genes in MRSA isolates recovered from the anterior nares over an 8-year period. This change in the frequency of qacA/B genes is most likely due to patients in those years being exposed in prior admissions. Future studies need to further evaluate the implications of universal CHG daily bathing on MRSA qacA/B genes among hospitalized patients

A five year outbreak of methicillin-susceptible Staphylococcus aureus phage type 53,85 in a regional neonatal unit

We identified a 5-year outbreak of a methicillin-susceptible Staphylococcus aureus (MSSA) strain, affecting 202 babies on a neonatal unit, by routine weekly phage typing all S. aureus isolates. Multiple staged control measures including strict emphasis on hand hygiene, environmental and staff surveillance sampling, and application of topical hexachlorophane powder failed to end the outbreak. S. aureus PT 53,85 (SA5385) was found on opened packs of Stomahesive®, used as a neonatal skin protectant. Only following the implementation of aseptic handling of Stomahesive®, and the use of topical mupirocin for staff nasal carriers of SA5385, and for babies colonized or infected with S. aureus, did the isolation rate of SA5385 decline. DNA fingerprinting indicated that [gt-or-equal, slanted]95% of SA5385 isolates were clonal. In vitro death rates of SA5385 on Stomahesive® with human serum were significantly lower than on Stomahesive® alone (P = 0·04), and on cotton sheet with serum (P = 0·04), highlighting the potential of this material as a survival niche. Phage typing remains a valuable, inexpensive and simple method for monitoring nosocomial MSSA infection

Risk Factors Associated with Mupirocin Resistance in Methicillin-Resistant Staphylococcus aureus

Implementation of meticillin-resistant Staphylococcus aureus (MRSA) decolonisation programmes has been increasing and the emergence of mupirocin resistance has been reported. However, the patient-level risk factors associated with mupirocin resistance are not clear. In this study, independent predictors of mupirocin resistance in MRSA among Providence Veterans Affairs Medical Center patients with MRSA-positive culture dates between 1 July 2004 and 30 June 2008 were identified using a frequency-matched case–control study. Forty cases (mupirocin-resistant) were matched on culture date quarter and year to 270 controls (mupirocin-susceptible). The adjusted conditional logistic regression model identified three significant independent predictors associated with mupirocin resistance in MRSA: (1) exposure to mupirocin in the year prior to the culture date [odds ratio (OR): 9.84; 95% confidence interval (CI): 2.93–33.09]; (2) Pseudomonas aeruginosa infection in the year before the culture-related admission (4.85; 1.20–19.61); and (3) cefepime use in the year prior to culture (2.80; 1.03–7.58). In sensitivity analyses, previous mupirocin exposure was associated with low-level [minimum inhibitory concentration (MIC) 8–128 mg/L; 23 cases, 202 controls; OR: 6.32; 95% CI: 1.58–25.33] and high-level (MIC ≥256 mg/L; 17 cases, 151 controls; OR: 11.18; 95% CI: 1.89–66.30) mupirocin resistance. To our knowledge, this is the first case–control study to reveal a strong association between previous mupirocin exposure and subsequent mupirocin resistance in MRSA, with demonstrated robustness in low- and high-level mupirocin resistance. Mupirocin susceptibility monitoring is critical for facilities instituting decolonisation with mupirocin as increased use may reduce effectiveness through resistance

Susceptibility of staphylococci isolated from a burns unit to mupirocin and other antimicrobial agents

The activity of mupirocin (Bactroban) against coagulase-positive and coagulase-negative staphylococci isolated in a burns unit was tested to ascertain its effectiveness, and to detect any resistant isolates after continuous use of mupirocin for 2.5 years. A total of 395 staphylococci, consisting of 330 Staphylococcus aureus and 65 coagulase-negative staphylococci, were tested for resistance to mupirocin and other antimicrobial agents. The results showed that 94.5% of the isolates were fully susceptible to mupirocin (MIC ≤4 mg/l), and 5.3% expressed low-level resistance (MIC 8-128 mg/l). One Staphylococcus haemolyticus isolate expressed high-level resistance (MIC >1,024 mg/l). It transferred high-level mupirocin resistance to other staphylococci in conjugation experiments, which indicated a capacity to transmit mupirocin resistance between species. The results demonstrated that mupirocin was still highly effective against staphylococci in the burns unit. However, the demonstration that the resistant S. haemolyticus isolate could transfer high-level mupirocin resistance to other staphylococci was of concern. There is a compelling need to test staphylococci from clinical materials for mupirocin resistance. Early detection of resistance can prevent the establishment and spread of the mupirocin-resistant strains in the unit

Stability of bacteriophages in burn wound care products

Bacteriophages could be used along with burn wound care products to enhance antimicrobial pressure during treatment. However, some of the components of the topical antimicrobials that are traditionally used for the prevention and treatment of burn wound infection might affect the activity of phages. Therefore, it is imperative to determine the counteraction of therapeutic phage preparations by burn wound care products before application in patients. Five phages, representatives of two morphological families (Myoviridae and Podoviridae) and active against 3 common bacterial burn wound pathogens (Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus) were tested against 13 different products commonly used in the treatment of burn wounds. The inactivation of the phages was quite variable for different phages and different products. Majority of the anti-infective products affected phage activity negatively either immediately or in the course of time, although impact was not always significant. Products with high acidity had the most adverse effect on phages. Our findings demonstrate that during combined treatment the choice of phages and wound care products must be carefully defined in advance

Theoretical Study of the Pseudomonic and Monic Acids

The drug Mupirocin has shown positive effects against both Gram-negative and Gram-positive bacteria with varying levels of success. It has been shown to be effective against Methicillin-Resistant Staphylococcus Aureas (MRSA) as a topical treatment in high concentrations. Mupirocin is comprised of pseudomonic acids. The monic acids are structurally similar to the pseudomonic acids and thus function as a good model to better understand the chemical characteristics of the drug. This work presents results of DFT (B3LYP) calculations with an accurate basis set on monic acid A and related species with focus on internal rotation barriers, optimal geometries, IR and Raman spectra, and electrostatic potentials to identify the differences between the monic and pseudomonic acids with an eye towards potential antibacterial treatments

Mupirocin and chlorhexidine resistance in Staphylococcus aureus in patients with community-onset skin and soft tissue infections

Decolonization measures, including mupirocin and chlorhexidine, are often prescribed to prevent Staphylococcus aureus skin and soft tissue infections (SSTI). The objective of this study was to determine the prevalence of high-level mupirocin and chlorhexidine resistance in S. aureus strains recovered from patients with SSTI before and after mupirocin and chlorhexidine administration and to determine whether carriage of a mupirocin- or chlorhexidine-resistant strain at baseline precluded S. aureus eradication. We recruited 1,089 patients with community-onset SSTI with or without S. aureus colonization. In addition to routine care, 483 patients were enrolled in a decolonization trial: 408 received intranasal mupirocin (with or without antimicrobial baths), and 258 performed chlorhexidine body washes. Patients were followed for up to 12 months with repeat colonization cultures. All S. aureus isolates were tested for high-level mupirocin and chlorhexidine resistance. At baseline, 23/1,089 (2.1%) patients carried a mupirocin-resistant S. aureus strain and 10/1,089 (0.9%) patients carried chlorhexidine-resistant S. aureus. Of 4 patients prescribed mupirocin, who carried a mupirocin-resistant S. aureus strain at baseline, 100% remained colonized at 1 month compared to 44% of the 324 patients without mupirocin resistance at baseline (P = 0.041). Of 2 patients prescribed chlorhexidine, who carried a chlorhexidine-resistant S. aureus strain at baseline, 50% remained colonized at 1 month compared to 48% of the 209 patients without chlorhexidine resistance at baseline (P = 1.0). The overall prevalence of mupirocin and chlorhexidine resistance is low in S. aureus isolates recovered from outpatients, but eradication efforts were less successful in patients carrying a mupirocin-resistant S. aureus strain at baseline