How long hospitalized for sepsis

Because both facility-level and patient-level data in the HDD are nonidentifiable, it was determined this work did not constitute research involving human subjects. All data were analyzed using SAS software, version 9.

Among hospitals, we identified randomly selected index stays among adults. Of those patients, 8. Of the remaining patients with index stays, 0.

Patients with severe sepsis within 90 days of an index stay had a mean length of stay of For patients with an infection or CDI diagnosis for the index stay, the unadjusted proportion of patients with subsequent severe sepsis was higher than that of patients without infection or a CDI diagnosis 0.

Among patients with exposure to a high-risk antibiotic agent during the index stay, the proportion of patients with severe sepsis after discharge was 0. Exposure to low-risk or control antibiotic agents was not associated with an increased risk of sepsis compared with patients not exposed to any antibiotics in the unadjusted analysis Table 1. In the multivariable logistic model, exposure to a high-risk antibiotic was associated with a higher risk of severe sepsis within 90 days of discharge than in our referent group odds ratio [OR], 1.

Exposure to low-risk and control antibiotic agents was not as strongly associated with severe sepsis OR, 1. Furthermore, both the number of unique antibiotics classes and total days of antibacterial therapy demonstrated a significant dose-response association with postdischarge severe sepsis. Similar results were found for our secondary outcome Table 3. In contrast, when using any readmission within 90 days as the outcome, the association between a high-risk antibiotic and readmission was close to 1 OR, 1.

We also limited the analysis to those with an infection-related primary discharge code during the index stay. Dose responses were observed when our analysis was limited to one of these groups Table 3. We found a significant association between antibiotic exposure in the hospital and severe sepsis and septic shock either as the cause of or occurring during a subsequent hospitalization within 90 days of discharge.

Furthermore, significant dose-response effects were observed for the number of antibiotic classes a patient received during the index hospitalization as well as the total duration of therapy. In contrast, the risk of postdischarge sepsis for exposure to low-risk antibiotics was diminished.

Our findings support, but do not prove, the hypothesis that microbiota disruption is associated with an increased risk of severe sepsis and septic shock within 90 days of discharge from a hospital stay. Prescott et al [ 16 ] previously demonstrated that the rate of sepsis 90 days after hospitalization was 3-fold greater than during other observation periods; they also found that hospital events, such as infection or CDI, further increased this rate.

Our study further supports this hypothesis by showing that increased antibiotic exposure or exposure to specific antibacterial agents more likely to disrupt the microbiota is associated with an increased risk in severe sepsis in the 90 days after hospital discharge. Unlike Prescott et al [ 16 ], we were able to include hospital pharmacy data, which was previously shown to be consistent with other estimates of hospital antibiotic usage and a representative sample of hospitals in the US [ 12 ].

In addition, we determined a priori the antibiotic exposure categories based on their epidemiologic association with clinically important microbiome disruption ie, CDI risk. Although the types of antibiotic-mediated disruptions that predispose to sepsis may ultimately be determined to be different from those that predispose to CDI, hypothesis-driven a priori analyses based on a theoretical framework may lessen the risk for unmeasured bias or spurious associations based on chance alone.

We were also able to control for a number of demographic and clinical characteristics, including certain chronic conditions likely to be associated with antibiotic use and hospital readmission in our multivariable models. In sensitivity analyses, we found estimates similar to those of Prescott et al [ 16 ], comparing infection-related or CDI-related hospitalizations with non—infection-related hospitalizations without adjustment for our antimicrobial exposures.

We also eliminated patients with an ICDCM code for CDI during either the index visit or the postdischarge sepsis visit and found consistent results with our primary model, suggesting that our association was not confounded by the well-described relationship between antibiotics and CDI.

However, additional epidemiologic and biologic studies may further explore this hypothesis. Antibiotic-mediated gut microbiota disruptions may increase the risk of sepsis via any one or a combination of 3 broad pathways. The first of these is loss of direct inhibition and competitive nutrient utilization, leading to loss of colonization resistance against more virulent and potentially pathogenic microbiota members [ 9 ]. Another pathway emphasizes the loss of immune-regulatory dampening functions of the gut microbiota itself, whereby, at least theoretically, antibiotic effects on the gut microbiota may contribute to a more pronounced septic response from even a non—gut-related site of primary infection [ 5 ].

A third pathway is loss of integrity of the gut mucosal barrier function, largely due to loss of short-chain fatty acids normally produced by a healthy microbiota that serve as the main nutrient source for large intestinal enterocytes [ 26 ]. Direct adverse drug events, such as allergic reactions and toxic effects like tendon rupture or renal toxicity, as well as the microbiota-mediated effects of antibiotic-associated diarrhea and especially CDI, are long-recognized forms of patient harm resulting from antibiotics [ 13 , 21 , 27 ].

Although the exact mechanisms remain under investigation, there is now a small but increasing body of human observational evidence and animal data suggesting broader detrimental effects on patient outcomes rooted in microbiota disruptions that result from antibiotic use, among other environmental insults [ 28 , 8 , 11 ].

Taur et al [ 29 ] showed that, even after controlling for confounders, 3-year mortality rates in bone marrow transplant recipients were associated with gut microbiota diversity at engraftment. In adult patients, the population evaluated in our study, poorer outcomes in patients with the systemic inflammatory response are associated with greater microbiota disruption [ 31 ].

One hope from our findings is that future innovations focused on restoring or protecting the lower intestinal microbiota from antibiotic-mediated disruption might become a possible approach for preventing sepsis [ 32 ]. Recent studies have established fecal microbiota transplantation as a front-line therapy for multiply recurrent CDI [ 33 ]. Despite at least 2 case reports of fecal microbiota transplantation apparently used successfully to treat sepsis [ 34 , 35 ], this remains highly experimental and carries unknown risk.

Although animal data suggest that a defined probiotic consortia could be developed to restore the barrier function of the gut and thereby possibly prevent antibiotic-mediated sepsis on that account [ 36 ], there are examples where probiotics administered in the throes of severe illness, specifically acute pancreatitis, have increased mortality risk [ 37 ].

Protecting the lower intestinal microbiota from antibiotic-mediated disruption may be another strategy available soon. However, another currently available prevention strategy is improved antibiotic stewardship.

In addition, recent studies suggest that certain common, serious infections may not need to be treated with broad-spectrum agents or with as many agents [ 44 ] or for as long a duration as previously thought [ 45 ]. The current study has several limitations.

First, administrative data such as the HDD are not collected for research purposes, and misclassification in the pharmacy, clinical, and facility data, including the use of ICDCM diagnostic codes, can lead to bias. However, this bias is probably nondifferential and would typically bias the results toward null values. Moreover, this type of pharmacy charge data was previously validated in small samples, with excellent agreement [ 46 , 47 ].

In addition, our outcome was based on ICDCM diagnostic codes, but this definition of sepsis was previously validated [ 24 ]. Although we controlled for several demographic and clinical characteristics in the multivariable analysis, residual confounding from unknown factors could affect our findings, particularly the presence of underlying conditions or characteristics that increase antibiotic use in the index hospitalization and the risk of subsequent infection.

However, in an analysis restricted to patients with no discharge diagnosis codes indicating an infection during the index hospitalization, our findings were similar, suggesting that an underlying predisposition to infection is less likely to confound our observed association.

Furthermore, when we included any readmission within 90 days as our outcome, instead of sepsis, we observed that the OR for our high-risk antibiotic group was reduced to nearly 1, providing additional support for our hypothesis, rather than underlying disease as the explanation for the association. In addition, we could include only postdischarge cases of sepsis in which patients returned to the same hospital, because patients in the HDD cannot be followed longitudinally across different hospitals.

As such, our estimate of the proportion of sepsis cases after hospitalization was smaller than that in the previous study, and death outside the same hospital was not detectable [ 16 ]. Finally, our study did not include any exposure data from healthcare encounters outside the hospital or antibiotics prescribed at discharge.

Given that a significant proportion of inpatient antimicrobial use may be unnecessary [ 14 , 48 ], this study builds on a growing evidence base suggesting that increased stewardship efforts in hospitals may not only prevent antimicrobial resistance, CDI, and other adverse effects, but may also reduce other unwanted outcomes potentially related to disruption of the microbiota, including sepsis.

The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention CDC. Financial support. This work was supported by the CDC. Potential conflicts of interest. All authors: No reported conflicts of interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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Share on: Facebook Twitter. Show references AskMayoExpert. Sepsis and septic shock. Mayo Clinic; Pomerantz WJ. Systemic inflammatory response syndrome SIRS and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis. Accessed Dec. Singer M, et al. The third international consensus definitions for sepsis and septic shock Sepsis Bennett JE, et al.

Elsevier; Neviere R. Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis. Page last reviewed: 18 July Next review due: 18 July Treatment for sepsis Sepsis needs treatment in hospital straight away because it can get worse quickly.

You should get antibiotics within 1 hour of arriving at hospital. You may need other tests or treatments depending on your symptoms, including: treatment in an intensive care unit a machine to help you breathe ventilator surgery to remove areas of infection You may need to stay in hospital for several weeks.

Recovering from sepsis Most people make a full recovery from sepsis.