mupirocin and Pneumonia

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 preoperative intranasal application of mupirocin significantly decreases the rate of nosocomial S. aureus infections among patients who are S. aureus carriers. However, it remains unclear whether the routine preoperative use of mupirocin would reduce postoperative S. aureus infections, especially methicillin-resistant Staphylococcus aureus (MRSA) infections, and who would benefit from the prophylactic use of mupirocin. Ninety-six consecutive patients who had undergone elective radical esophagectomy with right thoracotomy and laparotomy were evaluated. Fifty-one patients were given 2% mupirocin calcium ointment 3 times daily over 3 consecutive days before surgery. Uni- and multivariate analyses were performed to identify factors affecting the following three issues: postoperative MRSA infection, postoperative pneumonia, and the length of postoperative hospital stay. In univariate analyses, the preoperative application of mupirocin significantly reduced MRSA infection, postoperative pneumonia, and length of postoperative hospital stay. Multivariate analyses indicated significant associations between mupirocin administration and reductions in both MRSA infection and postoperative pneumonia, but not in length of postoperative hospital stay. Radical esophagectomy with right thoracotomy and laparotomy for esophageal carcinoma warranted the preoperative prophylactic administration of mupirocin in order to reduce postoperative infectious complications from MRSA. Its routine use for such a high-risk procedure is entirely reasonable.

Topics: Administration, Intranasal; Aged; Antibiotic Prophylaxis; Cross Infection; Esophagectomy; Female; Humans; Length of Stay; Male; Methicillin Resistance; Middle Aged; Mupirocin; Pneumonia; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus