Infectious Disease Updates
January 1, 2025
By Carol A. Kemper, MD, FIDSA
MDRO Colonization Increases Risk of Infection
Source: Alshubaily AM, Alosaimi AS, Alhothli BI, et al. Risk of invasive MDRO infection in MDRO-colonized patients. Infect Control and Hosp Epidemiol. 2024;Oct 14:1-5. doi:10.1017/ice.2024.156 [Online ahead of print].
These authors retrospectively examined the risk of clinically significant infection developing in patients with confirmed colonization with multi-drug resistant organisms (MDRO) at a large specialty hospital in Riyadh, Saudi Arabia, in 2021. This facility provides active surveillance for MDRO using rectal screening for carbapenemase-producing gram-negative organisms (CPO) and vancomycin-resistant Enterococci (VRE), and nasal and skin swabs for methicillin-resistant Staphylococcus aureus (MRSA), either on admission or at transfer to a higher level of care after seven days of hospitalization. Screening was performed using the GeneXpert polymerase chain reaction (PCR) system. A positive result automatically triggered contact isolation precautions in the electronic medical record. The positive result remains with the chart, and the patient remains in isolation during subsequent admissions until such time as cleared by infection prevention personnel based on discontinuation criteria. The risk of clinically significant infection was tracked for 365 days following a positive screening test result.
A total of 19,134 screening tests were included in the analysis (4,919 CPO, 8,303 MRSA, and 5,912 VRE). Among those tested for CPO, 445 patients (9%) had a positive PCR, sometimes for more than one carbapenemase-producing gene. The most commonly identified organism was OXA-48/NDM Klebsiella pneumoniae. Among those tested for MRSA and VRE, 10% and 14% were PCR positive, respectively. Patients with CPO and VRE were considerably older, whereas the mean age of MRSA PCR-positive patients was 38 years.
In the group screened for CPO, the risk of developing a clinically significant gram-negative infection in the next 365 days was significantly higher in those with a positive PCR result than in those without evidence of colonization (31% vs. 20.3%) (risk ratio, 1.5; confidence interval [CI], 1.3-1.8). The risk of developing a CPO-related infection also was significantly higher (10% vs. 2%; risk ratio, 4.6). Bloodstream infections were more likely in those with CPO colonization, and urine infections were more likely in those without recognized colonization. Gene testing demonstrated that 88% of the CPO infections in patients with colonization were the same organism as identified by rectal screening.
Colonization with VRE was 22 times more likely to result in active infection with VRE compared with patients without positive PCR rectal screens. Most of these were urine infections. The risk of MRSA infection was 8.2 times more likely in those with MRSA colonization compared to those with negative screening, and most of these were bloodstream infections. The risk of MRSA infection in those with colonization compared to those without was 2.8% vs. 0.3%.
Active screening for MDRO provides an opportunity for preemptive isolation of colonized patents, which may reduce transmission rates in hospital. It also allows for real-time antimicrobial stewardship, with improved antibiotic selection in patients with CPO colonization. During a one-year observation period, the risk of subsequent gram-negative infection in those with CPO rectal colonization was 31%, at least one-third of which was due to CPO — and this increased risk appears to be ongoing and long-term. Keep in mind that the sensitivity of rectal PCR screening for extended-spectrum beta-lactamase (ESBL)/carbapenem-resistant Enterobacterales (CRE) is variously reported from 67% to 94%, indicating failure to detect up to one-third of cases of MDRO colonization.
Peri-Operative Ertapenem
Source: Hostler CJ, Krishnan J, Parish A, et al. Postoperative outcomes after receipt of ertapenem antimicrobial prophylaxis for colon surgery: A multicenter retrospective cohort study. Infect Control Hosp Epidemiol. 2024;45:1-6.
Several regimens are currently recommended for peri-operative surgical prophylaxis of colon surgeries, including ertapenem, ampicillin-sulbactam, cefotetan, cefoxitin, ceftriaxone plus clindamycin or metronidazole, or a fluoroquinolone plus clindamycin or metronidazole for penicillin-allergic patients. Concerns have been raised about the risks of using a carbapenem agent for peri-operative purposes, since it is somewhat broader than the other agents and may have a greater effect on bowel flora as well as potential for inducing carbapenem resistance.
A retrospective multicenter cohort study was conducted to examine the use of ertapenem vs. alternate agents for peri-operative colon surgeries at seven academic and community hospitals in 2010-2015. Outcomes included the cumulative risk of surgical site infection (SSI) within 30 days of the procedure, the cumulative risk of developing Clostridioides difficile infection (CDI) within 30 days, and the risk of a positive culture for a carbapenem-resistant gram-negative organism (CRE).
A total of 2,109 surgical colon procedures were tracked, including 1,313 (62%) patients who received ertapenem for peri-operative prophylaxis and 796 (38%) who received alternate agents. These latter patients included those receiving either a first- or second-generation cephalosporin (17.8%), a fluoroquinolone plus clindamycin (16.3%), an anti-pseudomonal penicillin (11.5%), a third- or fourth-generation cephalosporin (0.8%), or ampicillin-sulbactam (0.2%). Significant differences were observed between the group receiving ertapenem and the group receiving alternate agents. Ertapenem was more likely to be used in patients with penicillin allergy, undergoing laparoscopy, having non-emergent procedures, with longer durations of surgery, and with clean contaminated wounds. Non-ertapenem agents were more likely to be used in patients undergoing emergent surgery and who had a higher risk of mortality.
In non-weighted analysis, a trend in increased SSI within 30 days was observed with the peri-operative use of ertapenem compared with alternate agents. SSI occurred in 46 patients (3.5%) receiving ertapenem vs. 20 patients (2.5%) receiving non-ertapenem agents. However, in various weighted analysis of risk, the risk of SSI was higher in the ertapenem group compared with the non-ertapenem group (odds ratio [OR], 1.56; confidence interval [CI], 1.08- 2.26; P = 0.02). Forty patients developed CDI (1.8%), including 1.8% of those receiving ertapenem and 2.0% of those receiving alternate agents. Initial analysis suggested no statistically significant difference in CDI risk between the two groups, but when inverse probability weights were added to the models, weighted analysis also found an increased risk of CDI in those receiving ertapenem compared with alternate agents (OR, 2.31; CI, 1.05-5.10; P = 0.04). The incidence of CRE was too low for comparison (two cases occurred in patients receiving ertapenem, and four cases occurred in patients receiving alternate agents).
Ertapenem for peri-operative prophylaxis may be an inferior choice to alternative agents. These data suggested an increased risk of SSI in weighted analysis, despite the fact that the ertapenem group was more likely to have non-emergent procedures compared with alternate group. One complicating factor to this analysis is the comment that 2% to 2.5% of patients received multiple agents, and another 3% to 6% received antibiotic treatment in the post-operative period. Although of interest, it is not clear whether this older retrospective data (from 2010-2015) can be generalized to 2025.
Whole-Genome Sequencing Shows Negligible Transmission of Clostridioides difficile in the ICU
Source: Miles-Jay A, Snitkin ES, Lin MY, et al. Longitudinal genomic surveillance of carriage and transmission of Clostridioides difficile in an intensive care unit. Nat Med 2023;29;2526-2534.
To gauge the risk of transmission of Clostridioides difficile (CD) organisms from patients with recognized colonization in the intensive care unit (ICU) setting, these authors performed peri-rectal swab or stool cultures for CD using enrichment media for all admissions during a nine-month period. Whole-genome sequencing (WGS) was performed on all recovered isolates. A total of 3,952 rectal swabs or culture specimens were obtained from 1,289 unique ICU admissions. A median of two samples were collected per ICU admission with a median length of stay of three days. The mean age was 62.7 years, most patients had a high comorbidity index, and 71.8% were exposed to antibiotics.
CD was found in at least one sample from 9.3% of admissions, for a total of 448 CD isolates. WGS was successfully performed on 425 of these. There were 32 culture-positive new events in non-colonized patients (“acquirers”). Seven (21.9%) of these appeared to be genetically linked to another patient isolate. While on the surface this suggested a possible linkage for a small number of acquired cases, only one (3%) could be clearly linked to a patient with recognized colonization. On further analysis, one of these events occurred 142 days following the index case and was believed to be unrelated. Two cases were acquired from other “acquirers” who were initially culture negative (but may have had occult colonization) and three cases were genomically linked to patients not captured by screening methods on admission.
These data suggest that most patients who develop active CD infection in the ICU setting do not acquire infection as the result of transmission from a recognized patient but are likely to have previous but unrecognized colonization. In other words, it was believed the risk of a falsely negative culture likely explained the majority of these new cases.
In our facility in Mountain View, CA, we have been tracking CD colonization in at-risk admissions (~12%) using real-time polymerase chain reaction (PCR). Less than 3% of colonized patients go on to develop active CD infection, although ~25% of our patients with hospital-onset CD were known to be recognized carriers. This suggests that the greatest opportunity for reducing hospital-onset CD infection may be on improved recognition of colonized cases and to focus interventions on reducing the risk of conversion to active infection for those patients with known carriage.
Carol A. Kemper, MD, FIDSA, is Medical Director, Infection Prevention, El Camino Hospital, Palo Alto Medical Foundation.
MDRO Colonization Increases Risk of Infection; Peri-Operative Ertapenem; Whole-Genome Sequencing Shows Negligible Transmission of Clostridioides difficile in the ICU
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