Episode 348: De-escalating anti-MRSA therapy in culture-negative nosocomial pneumonia, should low serum calcium be replaced by protocol in the ICU, and a tip for responding to inpatient medical emergencies

In this episode I’ll:

1. Discuss an article about de-escalating anti-MRSA therapy in culture-negative nosocomial pneumonia.

2. Answer the drug information question “Should low serum calcium be replaced by protocol in the ICU?”

3. Share a tip for responding to inpatient medical emergencies.

Article
Outcomes associated with de-escalating anti-MRSA therapy in culture-negative nosocomial pneumonia

Lead author: Maren C. Cowley

Currently in press with the journal Chest

Background

Prior studies of patients with culture-positive nosocomial pneumonia have demonstrated that antibiotic de-escalation from broad-spectrum empiric antimicrobials to narrower-spectrum agents decreases broad-spectrum antibiotic use without any effect on patient outcomes. However, in patients with culture-negative nosocomial pneumonia uncertainty exists regarding the safety of anti-MRSA agent de-escalation. The authors of this study sought to determine if anti-MRSA agent de-escalation in culture-negative nosocomial pneumonia affects 28-day and hospital mortality, ICU and hospital length of stay (LOS), treatment failure, and patient safety.

Methods

This study was a single-center retrospective cohort which included adult patients admitted over a 5 year period with nosocomial pneumonia and a negative respiratory culture. The authors defined de-escalation as anti-MRSA agent discontinuation within four days of initiation. The secondary outcomes included hospital mortality, hospital and ICU length of stay, treatment failure, and the occurrence of acute kidney injury (AKI).

Results

Of 279 patients included, 187 were in the de-escalation (DE) group and 92 were in the no de-escalation (NDE) group. Patients who were not de-escalated received 5 more days of MRSA coverage than patients who were de-escalated; however, there was no difference in 28-day mortality (NDE 28% vs DE 23%). Patients who were de-escalated had a shorter hospital (DE 15 days vs NDE 20 days) and ICU length of stay (DE 10 days vs NDE 13 days). The incidence of AKI was significantly higher in patients who were not de-escalated (DE 36% vs NDE 50%).

Conclusion

The authors concluded:

While anti-MRSA agent de-escalation in culture-negative nosocomial pneumonia did not affect 28-day mortality, it was associated with a shorter hospital stay and lower incidence of(AKI).

 

Discussion

This is an important study that helps to demonstrate the safety of anti-MRSA agent de-escalation in culture-negative nosocomial pneumonia.  Although mortality was unchanged, shorter length of stays and less AKI are clinically relevant outcomes.  The lack of effect on mortality actually strengthens the findings, in that less antibiotic use, shorter length of stay and less AKI can be achieved all without an adverse effect on patient mortality.   To qualify as de-escalation according to the study protocol, anti-MRSA therapy needed to be discontinued within 4 days.  This is a realistic time frame given the length of time it takes to determine if cultures are negative and suggests the study results are applicable to everyday practice.

Drug information question

Q: Should low serum calcium be replaced by protocol in the ICU?
A: I would consider not replacing calcium by protocol based on two articles:
An article in the journal CHEST concludes:

Dramatic curtailment of ionized calcium (iCa) measurement and calcium administration in several studies was not associated with worsening outcomes. The absence of high-quality data to guide practice allows for a spectrum of approaches to the measurement and treatment of iCa, but these approaches should be guided by basic principles of rational clinical decision-making. Widespread, protocolized measurement and administration with the simple goal of normalizing values in the name of “euboxia” should be discouraged.

And an article in Pharmacotherapy concludes:

Calcium administration correlated with adverse outcomes in critically ill patients receiving PN. The data suggest that administration of parenteral calcium to critically ill patients may be harmful.

Specific scenarios where monitoring and replacement of calcium are warranted include hypomagnesemia, massive transfusion (due to the citrate anticoagulants in the transfused blood which chelate calcium), parathyroid disease, and drug effect (such as from cisplatin).

Tip for responding to inpatient medical emergencies

When a patient with status epilepticus does not respond to the first treatment that can be expected to stop the seizure, they are in refractory status epilepticus.

In this scenario, midazolam, propofol, pentobarbital, or ketamine are possible options to terminate the seizure.

With any of these options, respiratory failure is a real possibility and the patient will likely need to be intubated for protection of their airway.

If using midazolam, I give 0.2 mg/kg IV bolus followed by an infusion of 0.1 mg/kg/hr.  Beware of tachyphylaxis.

If using propofol, I give a 1 or 2 mg/kg IV bolus followed by an infusion titrated as high as necessary to stop the seizures.  Beware of propofol infusion syndrome & don’t use very high doses any longer than necessary.

If using pentobarbital, I give 5mg/kg IV over 10 minutes, followed by 1mg/kg/hr.  Beware of severe hypotension.

If using ketamine, I give a 2 or 3 mg/kg IV bolus followed by an infusion of at least 1 mg/kg/hr.

midazolam
propofol
pentobarbital
ketamine

To learn how to manage this and other inpatient medical emergencies, read my book, A Pharmacist’s Guide to Inpatient Medical Emergencies available at clinicalpharmacybooks.com.

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