Sepsis is a life-threatening condition that occurs when the body’s response to an infection damages its own tissues and organs. It leads to shock, multiple organ failure and death especially if not recognized early and treated promptly. Antibiotics are the first line of treatment for sepsis. However, sometimes antibiotics may not work well for sepsis due to various reasons.
Why antibiotics may not work for sepsis
There are a few key reasons why antibiotics may not work effectively for sepsis:
- Antibiotic resistance – The bacteria causing the infection may be resistant to the antibiotics being used. This resistance can develop through genetic changes in the bacteria or previous exposure to antibiotics.
- Delayed or inadequate antibiotic therapy – Antibiotics may not work if they are not started early or are not able to achieve adequate concentrations in the blood to kill the bacteria.
- Undrained infection source – Antibiotics cannot clear an infection if the source of infection such as an abscess is not drained.
- Impaired immune function – People who are immunocompromised may not be able to mount an effective immune response to clear the infection even with antibiotics.
- Presence of endotoxins – Even if bacteria are killed, endotoxins released from their cell walls can continue to drive the inflammatory response leading to organ damage.
What happens when antibiotics are ineffective for sepsis?
When antibiotics are not working effectively to treat sepsis, some key complications can develop:
- Progression of sepsis – Sepsis can worsen rapidly from sepsis to severe sepsis to septic shock as the infection spreads and the inflammatory response increases.
- Persistent fever – The fever from sepsis may continue despite antibiotics as the infection is not controlled.
- Ongoing organ dysfunction – Low blood pressure, kidney failure, respiratory failure can progress as sepsis continues unchecked.
- Worsening laboratory markers – Markers like C-reactive protein, procalcitonin and lactic acid may remain elevated showing uncontrolled infection.
- Deteriorating mental status – Confusion, delirium and eventually coma can develop as sepsis affects the brain.
Overall, inadequately treated sepsis spirals out of control with patients developing multi-organ failure, immune paralysis from excessive inflammation and eventually death.
How is sepsis treated when antibiotics are not working?
When antibiotics are ineffective against sepsis, the key steps in management include:
- Identify and treat the source of infection – It is critical to locate any untreated source of infection and intervene, such as draining abscesses or removing infected devices. This helps reduce the microbial load.
- Culture samples – Blood cultures, urine, sputum and other samples from potential sites of infection should be obtained to try to identify the pathogen and its antibiotic sensitivity profile.
- Add broad spectrum antibiotics – Broad spectrum antibiotics like carbapenems and vancomycin may be added to try to cover for resistant bacteria.
- Remove ineffective antibiotics – Antibiotics not working should be discontinued promptly after bacterial cultures identify resistant organisms.
- Consider alternative antibiotics – Options like linezolid, daptomycin or ceftaroline may be considered based on bacterial susceptibility.
- Control source of infection – This may involve surgery to debride infected dead tissue, remove infected medical devices, or divert infected fluids collections.
- Adjunctive therapies – Other therapies like intravenous immunoglobulin, corticosteroids, or colony stimulating factors may help modulate the immune response.
If all attempts to treat sepsis fail, the patient may require supportive care in an intensive care unit until either the infection clears or the patient dies from multiple organ failure. Palliative care may need to be considered if the chance of recovery is very low.
What are the chances of surviving if antibiotics are not working for sepsis?
The chances of surviving sepsis are significantly lower if antibiotics are not effective. Some key statistics on sepsis survival when antibiotics fail include:
- One study found only 10% survival in sepsis patients with pan-antibiotic resistance compared to 68% survival in those with susceptible bacteria.
- In septic shock, if appropriate antibiotics are delayed beyond the first hour, mortality increases by 7.6% for every hour of delay.
- Sepsis mortality ranges from 20-65% in general. With untreated drug resistance, mortality can approach 100%.
- Immunocompromised patients have a higher risk of unresponsive sepsis. One study found only 14% of neutropenic sepsis patients survived if antibiotics failed.
- Elderly patients above 65 years have higher mortality from sepsis especially if antibiotics are inadequate. They comprised 87% of deaths in one study.
Overall, lack of an effective antibiotic regimen sets the stage for an uncontrolled inflammatory response and high risk of mortality from sepsis. However, mortality is also affected by factors like how early sepsis was recognized, how quickly treatment was started, source control measures and supportive ICU care.
Preventing antibiotic resistant sepsis
To reduce the likelihood of antibiotic resistant sepsis where antibiotics may not work, some key prevention strategies include:
- Have Antibiotic Stewardship program in hospitals to optimize antibiotic prescribing. This prevents overuse of antibiotics which drives resistance.
- Develop new antibiotics effective against resistant gram-negative and gram-positive bacteria causing sepsis.
- Improve infection control practices during procedures, surgeries and in ICUs to prevent healthcare-acquired drug resistant infections.
- Rapidly diagnose and treat sepsis before it progresses to more severe stages. This may allow antibiotics to work before resistance develops.
- Increase public awareness to restrict over-the-counter antibiotic use, prevent self-medication and complete prescribed courses to minimize resistance.
- Advance research on alternative treatments like antibodies, probiotics, bacteriophages and antimicrobial peptides to treat or prevent sepsis.
With a multipronged approach, antibiotic resistance in sepsis-causing bacteria can be reduced. This would improve the effectiveness of antibiotics for treating sepsis and its outcomes. However, many new solutions are still needed given the ability of bacteria to rapidly develop resistance.
Case Studies
Case Study 1
John, a 52-year old accountant developed fever, chills and low blood pressure just two days after a routine dental cleaning. He was diagnosed with sepsis likely due to an infection introduced during the dental procedure. He was started on broad-spectrum antibiotics in the ICU but continued to deteriorate over the next few days.
Blood cultures eventually grew methicillin-resistant Staphylococcus aureus (MRSA) which was resistant to the initial antibiotics. The antibiotics were then changed to vancomycin and the infected heart valve was surgically replaced. After a prolonged ICU course, John recovered from the antibiotic-resistant sepsis though needed life-long antibiotics to prevent recurrence of MRSA infections.
Case Study 2
Mary, a 36-year old lawyer developed a high fever and confusion after a week-long course of antibiotics for pneumonia. She had low blood pressure and blood tests showed elevated white cell count, CRP and liver enzymes. She was diagnosed with sepsis likely from multidrug resistant hospital-acquired pneumonia.
Multiple broad-spectrum antibiotics were started but Mary continued to deteriorate over the next few days requiring pressors and mechanical ventilation. Antibiotics were escalated to meropenem and linezolid. However, the sepsis continued unabated. Mary ultimately passed away from multiple organ failure secondary to untreatable XDR bacterial sepsis.
Key Takeaways
- Antibiotics may not work in sepsis due to resistance, inadequate levels or undrained infection source. This leads to uncontrolled sepsis progression.
- Ineffective antibiotics in sepsis lead to persistent infection, worsening organ failure, difficult-to-treat shock and high mortality.
- Treating unresponsive sepsis involves identifying infection source, culturing samples, using alternate broad-spectrum antibiotics and controlling the source.
- Mortality rates from sepsis are significantly higher if antibiotics are unable to treat the infection ranging from 50% to near 100%.
- Preventing antibiotic resistance through stewardship and infection control is key to improve sepsis outcomes when antibiotics fail.
Conclusion
Sepsis can take a devastating course when antibiotics are ineffective against the causative bacteria. While some cases may still be salvaged by aggressive treatment, the prognosis is significantly worse compared to sepsis from antibiotic-susceptible organisms. Preventing overuse of antibiotics is crucial to reduce the development of antibiotic resistant sepsis where first-line antibiotics often fail leading to increased risk of mortality and morbidity. Continued research and development of novel agents and alternative therapies is also needed to improve clinical outcomes when antibiotics do not sufficiently treat sepsis.