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Do piperacillin/tazobactam and other antibiotics with inhibitory activity against Clostridium difficile reduce the risk for acquisition of C. difficile colonization?

Kundrapu S, Sunkesula VC, Jury LA, Cadnum JL, Nerandzic MM, Musuuza JS, Sethi AK, Donskey CJ - BMC Infect. Dis. (2016)

Bottom Line: For a subset of patients, in vitro inhibition of C. difficile (defined as a reduction in concentration after inoculation of vegetative C. difficile into fresh stool suspensions) was compared among antibiotic treatment groups.Patients receiving other inhibitory antibiotics were not less likely to be asymptomatic carriers than those receiving non-inhibitory antibiotics.Our findings suggest that piperacillin/tazobactam achieves sufficient concentrations in the intestinal tract to inhibit C. difficile colonization during therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Infectious Diseases Division, Case Western Reserve, University School of Medicine, Cleveland, Ohio, USA.

ABSTRACT

Background: Systemic antibiotics vary widely in in vitro activity against Clostridium difficile. Some agents with activity against C. difficile (e.g., piperacillin/tazobactam) inhibit establishment of colonization in mice. We tested the hypothesis that piperacillin/tazobactam and other agents with activity against C. difficile achieve sufficient concentrations in the intestinal tract to inhibit colonization in patients.

Methods: Point-prevalence culture surveys were conducted to compare the frequency of asymptomatic rectal carriage of toxigenic C. difficile among patients receiving piperacillin/tazobactam or other inhibitory antibiotics (e.g. ampicillin, linezolid, carbapenems) versus antibiotics lacking activity against C. difficile (e.g., cephalosporins, ciprofloxacin). For a subset of patients, in vitro inhibition of C. difficile (defined as a reduction in concentration after inoculation of vegetative C. difficile into fresh stool suspensions) was compared among antibiotic treatment groups.

Results: Of 250 patients, 32 (13 %) were asymptomatic carriers of C. difficile. In comparison to patients receiving non-inhibitory antibiotics or prior antibiotics within 90 days, patients currently receiving piperacillin/tazobactam were less likely to be asymptomatic carriers (1/36, 3 versus 7/36, 19 and 15/69, 22 %, respectively; P = 0.024) and more likely to have fecal suspensions with in vitro inhibitory activity against C. difficile (20/28, 71 versus 3/11, 27 and 4/26, 15 %; P = 0.03). Patients receiving other inhibitory antibiotics were not less likely to be asymptomatic carriers than those receiving non-inhibitory antibiotics.

Conclusions: Our findings suggest that piperacillin/tazobactam achieves sufficient concentrations in the intestinal tract to inhibit C. difficile colonization during therapy.

No MeSH data available.


Related in: MedlinePlus

In vitro growth of Clostridium difficile in stool suspensions of hospitalized patients, stratified by level of in vitro inhibitory activity against C. difficile based on a modification of the classification of Owens et al. (1). A total of 141 stool specimens from 98 patients were analyzed (1–3 per patient). Specimens were considered inhibitory if the concentration of C. difficile decreased or remained unchanged compared to the baseline concentration. The non-inhibitory antibiotics that were administered at the time stool specimens were collected included ciprofloxacin (N = 6), ceftriaxone (N = 5), and cephalexin (N = 1). The agents classified as other inhibitory antibiotics that were administered included imipenem (N = 6), meropenem (N = 5), ertapenem (N = 6), linezolid (N = 4), ampicillin/sulbactam (N = 3), and metronidazole (N = 2). SE, standard error. CFU, colony-forming unit
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Fig2: In vitro growth of Clostridium difficile in stool suspensions of hospitalized patients, stratified by level of in vitro inhibitory activity against C. difficile based on a modification of the classification of Owens et al. (1). A total of 141 stool specimens from 98 patients were analyzed (1–3 per patient). Specimens were considered inhibitory if the concentration of C. difficile decreased or remained unchanged compared to the baseline concentration. The non-inhibitory antibiotics that were administered at the time stool specimens were collected included ciprofloxacin (N = 6), ceftriaxone (N = 5), and cephalexin (N = 1). The agents classified as other inhibitory antibiotics that were administered included imipenem (N = 6), meropenem (N = 5), ertapenem (N = 6), linezolid (N = 4), ampicillin/sulbactam (N = 3), and metronidazole (N = 2). SE, standard error. CFU, colony-forming unit

Mentions: Figure 2 provides a comparison of the proportions of fecal suspensions that were inhibitory to in vitro growth of C. difficile strain VA 17 and the mean (+/− standard error) change in C. difficile concentration, stratified by the type of antibiotic treatment. One-hundred forty-one stool specimens collected from 98 total patients were analyzed (1–3 per patient). In comparison to suspensions from patients on non-inhibitory antibiotics or with prior antibiotic exposure within 90 days, current piperacillin/tazobactam therapy was associated with more frequent inhibition of C. difficile growth (71 versus 27 and 44 %, respectively; P = 0.03). In contrast, only 30 % of stool suspensions from patients with prior rather than current piperacillin/tazobactam therapy were inhibitory to C. difficile growth; the time of collection of the specimens after discontinuation of piperacillin/tazobactam ranged from 1 to 7 days. Suspensions from patients on other inhibitory antibiotics were associated with more frequent inhibition in comparison to suspensions from patients with prior antibiotic exposure (P = 0.004), but not in comparison to suspensions from patients on non-inhibitory antibiotics (P = 0.14). Suspensions from patients on moxifloxacin were not associated with more frequent inhibition than suspensions from patients with prior antibiotic exposure or on non-inhibitory antibiotics (P = 0.07).Fig. 2


Do piperacillin/tazobactam and other antibiotics with inhibitory activity against Clostridium difficile reduce the risk for acquisition of C. difficile colonization?

Kundrapu S, Sunkesula VC, Jury LA, Cadnum JL, Nerandzic MM, Musuuza JS, Sethi AK, Donskey CJ - BMC Infect. Dis. (2016)

In vitro growth of Clostridium difficile in stool suspensions of hospitalized patients, stratified by level of in vitro inhibitory activity against C. difficile based on a modification of the classification of Owens et al. (1). A total of 141 stool specimens from 98 patients were analyzed (1–3 per patient). Specimens were considered inhibitory if the concentration of C. difficile decreased or remained unchanged compared to the baseline concentration. The non-inhibitory antibiotics that were administered at the time stool specimens were collected included ciprofloxacin (N = 6), ceftriaxone (N = 5), and cephalexin (N = 1). The agents classified as other inhibitory antibiotics that were administered included imipenem (N = 6), meropenem (N = 5), ertapenem (N = 6), linezolid (N = 4), ampicillin/sulbactam (N = 3), and metronidazole (N = 2). SE, standard error. CFU, colony-forming unit
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835867&req=5

Fig2: In vitro growth of Clostridium difficile in stool suspensions of hospitalized patients, stratified by level of in vitro inhibitory activity against C. difficile based on a modification of the classification of Owens et al. (1). A total of 141 stool specimens from 98 patients were analyzed (1–3 per patient). Specimens were considered inhibitory if the concentration of C. difficile decreased or remained unchanged compared to the baseline concentration. The non-inhibitory antibiotics that were administered at the time stool specimens were collected included ciprofloxacin (N = 6), ceftriaxone (N = 5), and cephalexin (N = 1). The agents classified as other inhibitory antibiotics that were administered included imipenem (N = 6), meropenem (N = 5), ertapenem (N = 6), linezolid (N = 4), ampicillin/sulbactam (N = 3), and metronidazole (N = 2). SE, standard error. CFU, colony-forming unit
Mentions: Figure 2 provides a comparison of the proportions of fecal suspensions that were inhibitory to in vitro growth of C. difficile strain VA 17 and the mean (+/− standard error) change in C. difficile concentration, stratified by the type of antibiotic treatment. One-hundred forty-one stool specimens collected from 98 total patients were analyzed (1–3 per patient). In comparison to suspensions from patients on non-inhibitory antibiotics or with prior antibiotic exposure within 90 days, current piperacillin/tazobactam therapy was associated with more frequent inhibition of C. difficile growth (71 versus 27 and 44 %, respectively; P = 0.03). In contrast, only 30 % of stool suspensions from patients with prior rather than current piperacillin/tazobactam therapy were inhibitory to C. difficile growth; the time of collection of the specimens after discontinuation of piperacillin/tazobactam ranged from 1 to 7 days. Suspensions from patients on other inhibitory antibiotics were associated with more frequent inhibition in comparison to suspensions from patients with prior antibiotic exposure (P = 0.004), but not in comparison to suspensions from patients on non-inhibitory antibiotics (P = 0.14). Suspensions from patients on moxifloxacin were not associated with more frequent inhibition than suspensions from patients with prior antibiotic exposure or on non-inhibitory antibiotics (P = 0.07).Fig. 2

Bottom Line: For a subset of patients, in vitro inhibition of C. difficile (defined as a reduction in concentration after inoculation of vegetative C. difficile into fresh stool suspensions) was compared among antibiotic treatment groups.Patients receiving other inhibitory antibiotics were not less likely to be asymptomatic carriers than those receiving non-inhibitory antibiotics.Our findings suggest that piperacillin/tazobactam achieves sufficient concentrations in the intestinal tract to inhibit C. difficile colonization during therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Infectious Diseases Division, Case Western Reserve, University School of Medicine, Cleveland, Ohio, USA.

ABSTRACT

Background: Systemic antibiotics vary widely in in vitro activity against Clostridium difficile. Some agents with activity against C. difficile (e.g., piperacillin/tazobactam) inhibit establishment of colonization in mice. We tested the hypothesis that piperacillin/tazobactam and other agents with activity against C. difficile achieve sufficient concentrations in the intestinal tract to inhibit colonization in patients.

Methods: Point-prevalence culture surveys were conducted to compare the frequency of asymptomatic rectal carriage of toxigenic C. difficile among patients receiving piperacillin/tazobactam or other inhibitory antibiotics (e.g. ampicillin, linezolid, carbapenems) versus antibiotics lacking activity against C. difficile (e.g., cephalosporins, ciprofloxacin). For a subset of patients, in vitro inhibition of C. difficile (defined as a reduction in concentration after inoculation of vegetative C. difficile into fresh stool suspensions) was compared among antibiotic treatment groups.

Results: Of 250 patients, 32 (13 %) were asymptomatic carriers of C. difficile. In comparison to patients receiving non-inhibitory antibiotics or prior antibiotics within 90 days, patients currently receiving piperacillin/tazobactam were less likely to be asymptomatic carriers (1/36, 3 versus 7/36, 19 and 15/69, 22 %, respectively; P = 0.024) and more likely to have fecal suspensions with in vitro inhibitory activity against C. difficile (20/28, 71 versus 3/11, 27 and 4/26, 15 %; P = 0.03). Patients receiving other inhibitory antibiotics were not less likely to be asymptomatic carriers than those receiving non-inhibitory antibiotics.

Conclusions: Our findings suggest that piperacillin/tazobactam achieves sufficient concentrations in the intestinal tract to inhibit C. difficile colonization during therapy.

No MeSH data available.


Related in: MedlinePlus