mupirocin and Sepsis

Topics: Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents, Local; Disease Transmission, Infectious; Germany; Gloves, Protective; Hand Disinfection; Hospitalization; Humans; Incidence; Infant, Newborn; Infection Control; Intensive Care Units; Intensive Care Units, Neonatal; Methicillin-Resistant Staphylococcus aureus; Mupirocin; Nose; Patient Isolation; Randomized Controlled Trials as Topic; Risk Factors; Sepsis; Staphylococcal Infections

Staphylococcus aureus is the pathogen most often isolated from blood during bacteraemic episodes in haemodialysis patients (42%). The pathophysiology of these infections is discussed and a prophylactic strategy is proposed. Nasal carriage of S. aureus, found in 42% of haemodialysis patients, plays a major role in its cutaneous dissemination and hence in the risk of infection by this microorganism. Long-term use of nasal mupirocin in haemodialysis patients with nasal carriage of S. aureus (t.i.d. for 3 to 5 days, followed by once a week) led to a decrease in the yearly incidence of S. aureus bacteraemia from 0.097 to 0.024 (p < 0.01). Tolerance was excellent. This chemoprophylaxis results in substantial savings. When applied as proposed (only nasal application), the long-term use of mupirocin only very rarely leads to the emergence of mupirocin-resistance in S. aureus (1 case in 165 patient-years).

Topics: Arteriovenous Shunt, Surgical; Carrier State; Catheterization, Central Venous; Catheters, Indwelling; Humans; Incidence; Mupirocin; Nasal Cavity; Renal Dialysis; Sepsis; Skin; Staphylococcal Infections; Staphylococcus aureus

Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization.. To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing.. Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included.. Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline).. ICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%.. Among the 801 668 admissions in 233 ICUs, the participants' mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P < .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]).. Nasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin.. ClinicalTrials.gov Identifier: NCT03140423.

Topics: Administration, Intranasal; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Infective Agents, Local; Baths; Chlorhexidine; Cross Infection; Female; Humans; Intensive Care Units; Iodophors; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Mupirocin; Pragmatic Clinical Trials as Topic; Sepsis; Staphylococcal Infections; Staphylococcus aureus; United States

Carbapenem-resistant Klebsiella pneumoniae isolates classified as multilocus sequence type 258 (ST258) are a problem in health care settings in many countries globally. ST258 isolates are resistant to multiple classes of antibiotics and can cause life-threatening infections, such as pneumonia and sepsis, in susceptible individuals. Treatment strategies for such infections are limited. Understanding the response of K. pneumoniae to host factors in the presence of antibiotics could reveal mechanisms employed by the pathogen to evade killing in the susceptible host, as well as inform treatment of infections. Here, we investigated the ability of antibiotics at subinhibitory concentrations to alter K. pneumoniae capsular polysaccharide (CPS) production and survival in normal human serum (NHS). Unexpectedly, pretreatment with some of the antibiotics tested enhanced ST258 survival in NHS. For example, a subinhibitory concentration of mupirocin increased survival for 7 of 10 clinical isolates evaluated and there was increased cell-associated CPS for 3 of these isolates compared with untreated controls. Additionally, mupirocin pretreatment caused concomitant reduction in the deposition of the serum complement protein C5b-9 on the surface of these three isolates. Transcriptome analyses with a selected ST258 isolate (34446) indicated that genes implicated in the stringent response and/or serum resistance were upregulated following mupirocin treatment and/or culture in NHS. In conclusion, mupirocin and/or human serum causes changes in the K. pneumoniae transcriptome that likely contribute to the observed decrease in serum susceptibility via a multifactorial process. Whether these responses can be extended more broadly and thus impact clinical outcome in the human host merits further investigation.

Topics: Anti-Bacterial Agents; Humans; Klebsiella Infections; Klebsiella pneumoniae; Mupirocin; Pneumonia; Sepsis

The synthesis, antibacterial activities, murine pharmacokinetic and infection model data for a range of aryl and heteroaryl ketone derivatives of monic acid (2a) are reported. The best results were found for the 3-furyl and 2-methoxy thiazol-5-yl analogues.

Topics: Animals; Anti-Bacterial Agents; Humans; Ketones; Male; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Mupirocin; Sepsis; Staphylococcal Infections; Structure-Activity Relationship; Thiazoles

Semisynthetic analogues of pseudomonic acid A have been prepared containing a heterocyclyl substituted oxazole. Derivatives in which the heterocycle was thiophene, furan, pyridine, or isoxazole showed good antibacterial potency and were further evaluated in vivo. Both pharmacokinetic parameters and oral activity against an experimental intraperitoneal sepsis were superior to results obtained from previously described pseudomonic acid A derivatives.

Topics: Animals; Anti-Bacterial Agents; Furans; Humans; Isoxazoles; Mice; Mupirocin; Oxazoles; Pyrazoles; Pyridines; Sepsis; Staphylococcal Infections; Thiazoles; Thiophenes