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Brief Report
24 September 2018

Impact of Antibiotic Treatment on the Burden of Nasal Staphylococcus aureus among Hospitalized Patients

ABSTRACT

We examined the impact of systemic antibiotics on the burden of nasal Staphylococcus aureus in hospitalized patients. Of 1,482 patients, 237 (16%) had nasal methicillin-susceptible S. aureus (MSSA) and 92 (6%) had nasal methicillin-resistant S. aureus (MRSA) on admission. Treatment regimens that included agents with inhibitory activity against MRSA or MSSA significantly reduced the burden of carriage, whereas regimens lacking anti-MRSA activity, including fluoroquinolones, promoted MRSA overgrowth.

TEXT

Systemic antibiotic treatment plays a major role in promotion of colonization by health care-associated pathogens and in determining the burden of carriage (1). Antibiotic-induced overgrowth of pathogens may increase the risk for transmission (25). For example, an increased nasal burden of methicillin-resistant Staphylococcus aureus (MRSA) has been associated with environmental contamination (35) and contamination of intact skin (5). In contrast, antibiotics with inhibitory activity against pathogens may suppress colonization if sufficient concentrations are achieved at the site of colonization (1, 6). Use of such antibiotics may reduce the risk for transmission.
Hospitalized patients with methicillin-susceptible S. aureus (MSSA) or MRSA colonization often receive systemic antibiotics, but relatively few studies have examined the impact of antibiotic therapy on the nasal burden of colonization. In the 1980s and early 1990s, systemic fluoroquinolones (ofloxacin and ciprofloxacin) and clindamycin were shown to be more effective than β-lactam antibiotics and erythromycin in eradicating susceptible strains of MSSA and MRSA from the nares (7, 8). However, in a facility where most MRSA isolates were resistant to ciprofloxacin, use of fluoroquinolones or β-lactams promoted nasal overgrowth of MRSA in colonized patients (3). Here, we examined the impact of systematic antibiotic therapy on the burden of nasal carriage of MSSA and MRSA in hospitalized patients.
We conducted a cohort study of all patients admitted to the Cleveland Veterans Affairs Medical Center during a 3-month period. The study protocol was approved by the facility's Institutional Review Board. Informed consent was waived because there was no interaction with the patients. For routine MRSA surveillance for clinical purposes, BBL CultureSwabs (Becton Dickinson, Cockeysville, MD) were used to sample the anterior nares of all patients on admission, ward transfer, and discharge. The swabs were tested for the presence of MRSA using a commercial PCR assay for the mecA gene. After being processed by the microbiology laboratory, the discarded swabs were obtained, and quantitative cultures were performed to determine the presence and burden of S. aureus. Swabs negative for MRSA by PCR were plated on BBL CHROMagar (Becton Dickinson) for isolation of MSSA; swabs positive for MRSA were plated on BBL CHROMagar containing cefoxitin 6 μg/ml for isolation of MRSA. Colonies consistent with S. aureus were tested for coagulase production using a Staphaurex kit (Remel, Lenexa, KS). The numbers of MSSA or MRSA CFUs per swab were counted. Medical records were reviewed to obtain information on demographics, antibiotic therapy, and medical conditions. For purposes of analysis, patients were included only if data from ≥2 swabs were available; a maximum of 3 swabs per patient was analyzed.
We examined the impact of antibiotic treatment regimens that did or did not include agents with anti-MSSA or anti-MRSA activity on the burden of carriage in comparison with colonized patients who were not receiving antibiotics. Antibiotic regimens were measured as days of therapy and were included in the analysis if the admission nasal swab was collected before or within 2 h after initiation of treatment and at least 24 h of treatment was administered. The timing of antibiotic administration and nasal swab collection was available in the electronic medical record. Based on the facility's antibiogram, antibiotics on formulary were classified as those with anti-MRSA and anti-MSSA activity (vancomycin, daptomycin, linezolid, ceftaroline, clindamycin, doxycycline, and trimethoprim-sulfamethoxazole), anti-MSSA but not anti-MRSA activity (dicloxacillin, amoxicillin-clavulanic acid, piperacillin-tazobactam, ampicillin-sulbactam, cefazolin, ceftriaxone, cefepime, imipenem-cilastatin, meropenem, and ertapenem), and no antistaphylococcal activity (aztreonam, penicillin, amoxicillin). Fluoroquinolones have variable activity against S. aureus in our facility. Therefore, we measured MICs for fluoroquinolones prescribed in the absence of other agents with anti-MRSA activity versus the colonizing S. aureus strain recovered using Clinical and Laboratory Standards Institute (CLSI) guidelines (9). Student's t test was used to compare the mean CFUs present before versus during or after antibiotic treatment for agents with versus those without anti-MRSA or anti-MSSA activity with the change in the burden of colonization for patients not receiving antibiotic treatment.
Of 1,482 patients screened on admission, 329 (22%) had positive nasal cultures for S. aureus, including 237 (16%) with MSSA and 92 (6%) with MRSA. Paired samples were available for 185 patients (56%) with MSSA or MRSA carriage, including 128 (54%) patients carrying MSSA and 57 (62%) carrying MRSA. The lack of more paired samples was primarily due to samples not being saved in the microbiology lab or failure to record the date of collection. For the 185 patients with paired nasal culture samples, the mean age was 66 years, and 169 (91%) were males. Twenty-nine patients (51%) with MRSA carriage received antibiotic regimens with anti-MRSA activity, 9 patients (16%) received regimens with no MRSA activity, and 19 patients (33%) received no antibiotics. Forty-four patients (34%) with MSSA received antibiotic regimens with anti-MSSA activity, and 84 (66%) did not receive these antibiotics. Of the 7 patients who received fluoroquinolone treatment alone or in combination with agents lacking anti-MRSA activity, 6 (86%) carried isolates that were resistant to the fluoroquinolone being used. None of the patients received intranasal mupirocin or povidone iodine or topical chlorhexidine during the study period.
Figure 1, top, shows the effect of antibiotic treatment on the burden of nasal MRSA in MRSA-colonized patients, stratified by regimens that included anti-MRSA antibiotics, antibiotic regimens that did not include MRSA activity, or no antibiotics. The median times between the baseline and the first follow-up swabs and between the first and second follow-up swabs were 6.8 days (range, 1 to 30 days) and 6 days (range, 1 to 30 days), respectively. There was no change in the nasal burden of MRSA in patients who did not receive antibiotics (P > 0.05). Treatment with antibiotic regimens that included anti-MRSA activity significantly reduced the burden of nasal carriage on both the initial and the second follow-up cultures (P < 0.01). Treatment with regimens that did not include anti-MRSA activity, including fluoroquinolones, resulted in a significant increase in the burden of MRSA (P < 0.05). Agents with anti-MRSA activity used to treat the MRSA carriers included vancomycin (23 treatment regimens), trimethoprim-sulfamethoxazole (4 regimens), doxycycline (3 regimens), and ciprofloxacin (1 regimen); 2 patients received >1 agent with anti-MRSA activity as part of an anti-MRSA regimen. The median durations of treatment with agents with and without anti-MRSA activity were 4 days (range, 1 to 29 days) and 4 days (range, 1 to 29 days), respectively. For regimens with or without anti-MRSA activity, there was no significant difference in nasal burden of MRSA for treatment durations of 1, 2 to 4, or >4 days (data not shown).
FIG 1
FIG 1 Effect of antibiotic treatment on the burden of nasal methicillin-resistant Staphylococcus aureus (MRSA) (top) and methicillin-susceptible S. aureus (MSSA) (bottom) in colonized patients. For MRSA carriers, regimens are stratified by those containing anti-MRSA antibiotics, those containing antibiotics with no anti-MRSA activity, and no antibiotic treatment. For MSSA carriers, regimens containing anti-MSSA antibiotics are compared with no antibiotic treatment.
Figure 1, bottom, shows the effect of antibiotic treatment on the burden of nasal MSSA in MSSA-colonized patients, stratified by those who received regimens that included anti-MSSA activity or no antibiotics; no MSSA-colonized patients received an antibiotic regimen that did not include activity against MSSA. The median times between the baseline and the first follow-up swabs and between the first and the second follow-up swabs were 5.6 days (range, 1 to 29 days) and 4 days (range, 1 to 23 days), respectively. Treatment with regimens that included anti-MSSA activity significantly reduced the burden of nasal carriage on both initial and second follow-up cultures (P < 0.01), whereas there was no reduction in the nasal MSSA burden in colonized patients not receiving antibiotics (P > 0.05). Agents with anti-MSSA activity that were used to treat the MSSA carriers during the study period included vancomycin (19 treatment regimens), piperacillin-tazobactam (17 regimens), amoxicillin-clavulanic acid (5 regimens), cefazolin (18 regimens), ceftriaxone (8 regimens), and carbapenems (2 regimens); 25 patients received >1 agent with anti-MSSA activity as part of an anti-MSSA regimen. The median duration of treatment with agents with anti-MSSA activity was 5 days (range, 1 to 30 days). For regimens with anti-MSSA activity, there was no significant difference in nasal burden of MSSA for treatment durations of 1, 2 to 4, or >4 days (data not shown).
Our findings are consistent with those of previous studies in demonstrating the major impact of systematic antibiotic treatment on the burden of MRSA and MSSA in the nares of colonized patients. In the absence of antibiotic treatment, the burden of S. aureus was similar on admission and during the hospital stay. Treatment regimens that included various agents with inhibitory activity against MRSA or MSSA significantly reduced the burden of carriage, suggesting that sufficient concentrations were achieved to inhibit colonization. Antibiotic regimens lacking anti-MRSA activity, including fluoroquinolones, promoted overgrowth of MRSA, presumably due to suppression of competing indigenous microorganisms that limit overgrowth of MRSA (3). Previous studies demonstrated that systemic antibiotics may impact the nasopharyngeal microbiota (10).
Our findings have important clinical implications. Antibiotic-induced overgrowth of S. aureus isolates may increase the risk for transmission by increasing environmental or skin contamination (35). Increased burden of carriage on skin may also increase the risk for infection by facilitating S. aureus contamination of wounds or devices. In contrast, treatment with antibiotic regimens that include inhibitory activity against MRSA or MSSA may reduce the risk for transmission or infection if the nasal burden and shedding of staphylococci are reduced. Our results may contribute to stewardship interventions to select agents that are less likely to promote overgrowth of MSSA and MRSA. Future efforts are needed to develop approaches that reduce the adverse effects of antibiotics on the nasal microbiota or that restore the microbiota after antibiotic treatment.
Our study has some limitations. We did not obtain data for several agents of interest (e.g., linezolid, daptomycin, and ceftaroline) because these antibiotics were not used in the study cohort. We only obtained data during the patients' hospital stay, which typically lasted only a few days. Additional studies are needed to obtain information on the duration of the effect of antibiotics on the nasal burden of S. aureus. Finally, paired samples were available for only 56% of patients with MSSA or MRSA carriage on admission.

ACKNOWLEDGMENTS

This study was supported by the Department of Veterans Affairs.
C.J.D. has received research grants from Merck, Synthetic Biologics, and Pfizer. We have no other conflicts of interest to declare.

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Information & Contributors

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Published In

cover image Antimicrobial Agents and Chemotherapy
Antimicrobial Agents and Chemotherapy
Volume 62Number 10October 2018
eLocator: 10.1128/aac.00609-18

History

Received: 27 March 2018
Returned for modification: 12 May 2018
Accepted: 4 July 2018
Published online: 24 September 2018

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Keywords

  1. Staphylococcus aureus
  2. antibiotics
  3. nasal burden

Contributors

Authors

Anubhav Kanwar
Division of Infectious Diseases and HIV Medicine, University Hospitals Case Medical Center, Cleveland, Ohio, USA
Geriatric Research Education and Clinical Center, Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA
Research Service, Louis Stokes Veterans Affairs Medical Center, Cleveland, Ohio, USA
Jennifer L. Cadnum
Geriatric Research Education and Clinical Center, Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA
Research Service, Louis Stokes Veterans Affairs Medical Center, Cleveland, Ohio, USA
Annette L. Jencson
Geriatric Research Education and Clinical Center, Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA
Curtis J. Donskey
Geriatric Research Education and Clinical Center, Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA
Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

Notes

Address correspondence to Anubhav Kanwar, [email protected].

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