Evaluating the utility of procalcitonin and a clinical decision support tool to determine duration of antimicrobial therapy for respiratory tract infections.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Procalcitonin (PCT) levels may play a role in decreasing the duration of antimicrobial therapy in institutions that have long durations of therapy for management of community-acquired pneumonia. We assessed the impact of the combination of pharmacist stewardship interventions assisted by a clinical decision support (CDS) tool and PCT assessment on the antimicrobial days of therapy (DOT) prescribed for respiratory tract infections (RTIs). METHODS: We conducted a quasi-experimental study in which patients in the preintervention group were admitted between April and June 2021 and patients in the intervention group were admitted between April and June 2022. In the intervention phase, a CDS tool was utilized to alert clinical pharmacists when patients met specific criteria. This alert was programmed to activate for individual patients when a reported PCT level was less than 0.25 ng/mL and on antimicrobials prescribed for an RTI as indicated by providers in the electronic health record. Stewardship interventions were made by pharmacists via prospective audit and feedback. The primary endpoint was inpatient antimicrobial DOT for RTIs. RESULTS: There were 90 patients in the preintervention group and 104 patients in the intervention group. Although baseline characteristics were not well matched between the groups, favoring the preintervention group, the median DOT was lower in the intervention group at 3 days (interquartile range [IQR], 2-4 days), compared to 4 days (IQR, 2.8-5 days) in the preintervention group (P = 0.001). CONCLUSION: The results of our study demonstrate the utility of pharmacist interventions coupled with CDS and PCT in reducing antimicrobial DOT prescribed for RTIs. Antimicrobial stewardship programs may benefit from implementing a PCT bundle.

Evaluation of computerized clinical decision support system to reduce unnecessary nasal methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) testing.

Our health system implemented a novel clinical decision-support system to reduce unnecessary duplicate nasal methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) orders. In an 8-month period, the rate of duplicate MRSA PCR orders within 7 days declined from 4.7% (370 of 7,861) to 1.2% (120 of 9,833).

Comparison of antimicrobial utilization metrics: Food for thought for an antimicrobial stewardship programme.

Given the overuse of antimicrobials and increasing antimicrobial resistance, the World Health Organization and Centers for Disease Control and Prevention recommend antimicrobial stewardship programmes to measure and assess the use of antimicrobials. Several antimicrobial use metrics have been described, including days of therapy, defined daily doses and standardized antimicrobial administration ratio. Understanding these metrics, including the advantages and disadvantages, can help antimicrobial stewardship programmes to monitor antimicrobial use at their institution, and assess the impact of antimicrobial stewardship efforts. This review discusses the three commonly used antimicrobial use metrics, their pros and cons, and how antimicrobial stewardship programmes can use these metrics to help assess the use of antimicrobials.

Patient Case Report Daptomycin Holiday-A Daptomycin Dosing Strategy for Asymptomatic Increases in Creatine Phosphokinase Levels.

Daptomycin possesses excellent activity against many multidrug-resistant gram positive organisms. However, a side effect of concern with daptomycin is skeletal muscle injury, which is manifested in the form of elevated creatine phosphokinase (CPK). Management of such CPK elevations has traditionally been discontinuation of the offending agent, with many studies showing a resolution of a normal CPK level within 1 week of discontinuation and no long term adverse effects. Nevertheless, the question remains if daptomycin can be successfully restarted in such patients. Here, we present a case of a "daptomycin holiday" in which daptomycin was withheld upon CPK elevation and successfully reintroduced to the patient's regimen again after several days without further elevation of the CPK. The patient had a peak CPK of 2,557 U/L, and had no associated symptoms. A hypothesis for this holiday could be the adaptability of the skeletal muscle myocytes, in which the extra period between doses may allow for additional recovery of the membrane structure to further daptomycin exposure. Giving an asymptomatic patient with elevated CPK level, a short daptomycin holiday to allow for the CPK level to trend downward before resuming daptomycin therapy could be a potential strategy in patients for whom continuing daptomycin is still preferred.

Impact of Antimicrobial Stewardship Interventions on Antimicrobial Utilization in Asymptomatic Bacteriuria.

Background: Antimicrobial therapy for asymptomatic bacteriuria (ASB) is often unnecessary and is a common reason for inappropriate antimicrobial use in hospitalized patients. Unnecessary ASB treatment leads to collateral damage such as resistance, and Clostridium difficile infections. This study evaluated the impact of interdisciplinary antimicrobial stewardship interventions on antimicrobial utilization in ASB. Methods: This was a quasi-experimental institutional review board (IRB)-approved study evaluating the impact of antimicrobial stewardship on antibiotic utilization for ASB in a pilot medical-surgical unit. The control phase was from August-October 2017 and the postintervention phase was from December-March 2018. In the control phase, electronic medical records of patients with positive urine cultures were retrospectively reviewed. Patients were classified as either having ASB or urinary tract infection (UTI) based on the absence or presence of UTI symptoms documented in the medical record. The intervention phase consisted of educational in-services to providers, nurses, and pharmacists. Clinical pharmacists for the pilot unit utilized an electronic real-time surveillance system to identify patients with positive urine cultures. With nurses' collaboration, clinical pharmacists classified these patients as either having UTI or ASB. Stewardship interventions were made in real-time to discontinue antibiotics in patients with ASB. Results: There were 65 and 77 patients with bacteriuria in the pre- and postintervention phases. Among these, ASB was present in 29 (45%) and 27 (35%) patients, respectively. After excluding those receiving antibiotics for concurrent nonurinary indications, the combination of education with pharmacist and nursing interventions decreased unnecessary ASB treatment from 18 (62%) to 6 (22%) patients (relative risk: 0.36, 95% confidence interval: 0.16-0.72, P = .003). Conclusion: The findings of this study highlight the importance of interdisciplinary interventions in reducing unnecessary antimicrobial therapy for the treatment of ASB. With increasing antimicrobial resistance, healthcare institutions should evaluate the role of these interdisciplinary interventions to reduce unnecessary treatment for ASB.

Aztreonam, Ceftazidime/Avibactam, and Colistin Combination for the Management of Carbapenemase-Producing Klebsiella Pneumoniae Bacteremia: A Case Report.

PURPOSE: A case of a patient with sepsis from a urinary source due to carbapenemase-producing Klebsiella pneumoniae treated with a novel combination of aztreonam, ceftazidime/avibactam, and colistin is described. Summary: An 80-year-old South Asian male presented to the hospital with sepsis from a urinary source. Blood and urine cultures were positive for a carbapenemase-producing K pneumoniae sensitive only to colistin and tigecycline. Novel beta-lactamase inhibitor combinations ceftazidime/avibactam and meropenem/vaborbactam were resistant. Patient was initially on ceftazidime/avibactam and colistin combination followed by tigecycline and colistin with lack of improvement. Metallo-beta-lactamase (MBL)-producing K pneumoniae was suspected based on the sensitivity pattern and history of medical treatment in India. Patient was then initiated on novel combination of ceftazidime/avibactam, aztreonam, and colistin. Patient's white blood cell (WBC) count and fever curve normalized. Unfortunately, the patient failed to recover completely likely because of his multiple comorbidities and declining functional status, resulting in the family's decision to pursue hospice. CONCLUSION: The combination of ceftazidime/avibactam and aztreonam should be considered as a viable treatment option for patients with infections caused by MBL-producing Enterobacteriaceae.

First report of Tsukamurella endocarditis in an immunocompromised patient receiving chemotherapy.

Tsukamurella spp. are gram-positive rods that can be isolated from the environment in soil and moist areas. In rare instances, they are known to cause infections in immunocompromised hosts. We present the first reported case of Tsukamurella endocarditis in an immunocompromised patient who was successfully treated with a 6-week course of imipenem and trimethoprim-sulfamethoxazole.

Incorporation of rapid diagnostic tests to improve time to antimicrobial therapy for gram-positive bacteremia and candidemia.

PURPOSE: Even with rapid diagnostic technology to swiftly identify infectious organisms, prompt response is needed to translate results into appropriate actions. The purpose of this study was to determine if the introduction of real-time pharmacist response to positive rapid diagnostic test results would decrease time to antimicrobial therapy for gram-positive bacteremia and candidemia in a community hospital setting. METHODS: A quasi-experimental study was conducted in 2 community hospitals. The study comprised 2 cohorts of adult patients who tested positive for gram-positive bacteremia involving Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, or Candida species. The preintervention cohort consisted of patients admitted from November 2017 through May 2018. The intervention cohort consisted of patients admitted from July 2018 through January 2019, after the intervention went live. The primary outcomes were time to optimal antimicrobial therapy and time to effective antimicrobial therapy. RESULTS: A total of 140 patients were included in the preintervention group, with 124 patients included in the intervention group. The mean (SD) time to effective therapy decreased from 13.9 (21.6) hours in the preintervention group to 8.6 (12.5) hours in the intervention group (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.89-1.48; P = 0.29). The mean (SD) time to optimal therapy significantly decreased from 53.7 (57.7) hours in the preintervention group to 38.4 (31.5) hours in the intervention group (HR, 1.73; 95% CI, 1.33-2.26; P < 0.001). CONCLUSION: The introduction of real-time pharmacist response to positive rapid diagnostic test results led to a significant decrease in time to optimal antimicrobial therapy but did not significantly affect time to effective therapy. The results showed that the allocation of limited resources of a community hospital to such a stewardship program is justifiable.

Severe Plasmodium falciparum Malaria Treated With Investigational Artesunate in the United States.

PURPOSE: We describe here the case of a 40-year-old Nigerian male with severe Plasmodium falciparum malaria successfully treated with investigational intravenous (IV) artesunate. SUMMARY: A 40-year-old Nigerian male was admitted to the medical intensive care unit for the treatment of severe malaria. The patient presented with the classic malaria paroxysm and altered mental status and was in acute renal failure. A blood parasite, thick and thin smear was performed revealing positive ring forms on smear which are characteristic of Plasmodium falciparum, with an estimated parasitemia of 2%. Per the Centers for Disease Control and Prevention (CDC) guidelines, the recommended treatment for severe malaria is with IV quinidine, the only Food and Drug Administration (FDA)-approved medication available for the treatment of severe malaria in the United States. However, quinidine was not immediately available, including from surrounding hospitals. As a result, the infectious diseases physician and pharmacist decided to contact the CDC to initiate the process for obtaining IV artesunate, an investigational drug only available via a FDA-approved Investigational New Drug (IND) protocol. Artesunate was flown into Houston later that night, and this drug was administered successfully to the patient. Patient responded to treatment and was discharged from the hospital on day 4. CONCLUSION: A patient with severe falciparum malaria was successfully treated with investigational artesunate procured from the CDC.

A Case Report of Neurotoxicity After Prolonged Doses of Acyclovir in a Patient With Renal Dysfunction.

Renal dysfunction is a significant risk factor for acyclovir-induced neurotoxicity and altered mentation and myoclonic movements are the most common clinical symptoms observed. In majority of reported cases, neurological sequelae associated with acyclovir-induced neurotoxicity often mimic viral infections of the central nervous system and makes diagnosis of the former challenging. Although plasma concentrations of the drug may not always correlate with neurotoxic symptoms, obtaining serum levels of acyclovir may be helpful in confirming drug-induced neurotoxicity. Hemodialysis has been shown to significantly improve altered mentation in patients with suspected or confirmed acyclovir-induced neurotoxicity. Here, we report a definite case of acyclovir-induced neurotoxicity in a patient with end-stage renal disease. Clinical improvements in neurologic symptoms were observed following discontinuation of the drug and hemodialysis.

Frequency of troponin elevations in patients with influenza infection during the 2017-2018 influenza season.

BACKGROUND: With the increased number of influenza cases observed during the 2017 - 2018 season, patients may be at a greater risk of cardiac related complications as a sequela of viral illness. We described the frequency of troponin elevations in patients with influenza infection during the 2017 - 2018 influenza season. METHODS: This was a retrospective, single-center observational study. All patients aged 18 years or older and had laboratory confirmed influenza viral infection were included in the study. Troponins were considered elevated if greater than 0.3 ng/mL. Electronic health records were reviewed for demographics, laboratory values, coronary artery disease history, electrocardiography, echocardiography results, and incidence of inpatient mortality. RESULTS: A total of 1,131 patients had lab confirmed influenza infection. Majority of the influenza strains were influenza A, 76.2% (n = 863), and the rest of the influenza strains comprised of influenza B, 23.8% (n = 270). Thirty three (2.9%) patients had elevation of troponin levels greater than 0.3 ng/mL. Most of the patients with elevated troponin levels had influenza A infection (90.9%, n = 30), of which H3 subtype was the most common (48.5%, n = 16). Fifteen patients (45.5%) had a myocardial infarction, 20 (60.6%) had left ventricular abnormalities visualized on echocardiogram, and four (12.1%) died while inpatient. CONCLUSIONS: Our results describe the frequency of troponin elevations in patients with influenza infection at our institution during the 2017 - 2018 influenza season.

Pharmacotherapy for leishmaniasis in the United States: focus on miltefosine.

Leishmaniasis is a protozoan infection native to various countries, including those in South America and Southeast Asia. Although the incidence of leishmaniasis is low in the United States, it is an important cause of infection in individuals traveling to endemic areas. Various treatment modalities are available, depending on their availability in the geographic region. In the United States, the treatment of choice is considered to be liposomal amphotericin, although other therapies have been explored. In 2014, miltefosine became the first orally available medication approved for the treatment of leishmaniasis in the United States. Based on available data, miltefosine is a first-line option for the treatment of leishmaniasis. Miltefosine is equally efficacious to and may be as tolerable as liposomal amphotericin B. The most common adverse effects of miltefosine are vomiting, diarrhea, and transient liver enzyme level elevation. Miltefosine has not been readily available in the United States due to marketing delays and is expected to become available later this year. In the meantime, the drug may be obtained through the Centers for Disease Control and Prevention expanded-access investigational new drug protocol.

Role of intravenous immune globulin in streptococcal toxic shock syndrome and Clostridium difficile infection.

PURPOSE: The use of intravenous immune globulin (IVIG) in the management of streptococcal toxic shock syndrome (STSS) and Clostridium difficile infection (CDI) is reviewed. SUMMARY: IVIG has a wide range of uses in clinical practice, including STSS and CDI. It is an attractive option for these two infections because both infections are toxin mediated, and IVIG may contain antibodies that neutralize these toxins. For STSS and CDI, IVIG is often considered for use in critically ill patients who are not responding to traditional therapies. Several encouraging case reports and retrospective chart reviews have been published, highlighting the potential benefit of IVIG in such patients. However, its definitive role remains unclear, mainly due to the lack of high-level evidence. Data supporting its use have been extrapolated from retrospective chart reviews and case reports in which profound heterogeneity in patient populations and treatment modalities exist. The use of IVIG must be weighed carefully because it is not a benign product. As with the use of IVIG for STSS, the role of IVIG for CDI is unclear. Nonetheless, IVIG may serve as a useful adjunct therapy for patients suffering from severe complicated CDI (shock, ileus, or megacolon) who do not respond to conventional treatment. Adverse reactions to IVIG are mild and transitory and occur during or immediately after drug infusion. CONCLUSION: Although randomized, controlled trials supporting the use of IVIG for STSS and CDI are lacking, IVIG may be considered a last-line adjunct therapy in those patients for whom the clinical benefit outweighs the potential adverse effects of therapy.

Monitoring of Outpatient Parenteral Antimicrobial Therapy and Implementation of Clinical Pharmacy Services at a Community Hospital Infusion Unit.

BACKGROUND: In 2004, the Infectious Diseases Society of America (IDSA) published monitoring guidelines for outpatient parenteral antimicrobial therapy (OPAT), but no assessment of their utilization has been reported. We evaluated adherence to these recommendations by physicians at infusion centers and then piloted a program of supervision of monitoring by pharmacists. METHODS: Phase I: We performed a retrospective case-control study of patients who received OPAT over 1 year at 2 hospital infusion centers. Controls were patients treated by an infectious diseases (ID) physician, and cases were those without an ID physician. Patients were excluded if they received fewer than 3 days of OPAT. Clinical pharmacy monitoring services were then implemented for patients on OPAT prescribed by non-ID physicians at 1 hospital's infusion unit. Two outcomes were measured: adherence to guidelines on monitoring and attainment of goal vancomycin and aminoglycoside serum concentrations when appropriate. The results for non-ID physicians were compared to both ID physicians and subsequently a pharmacist. RESULTS: Ninety-nine patients were included in the retrospective study. Compared with patients who had ID physician supervision, the non-ID physicians who prescribed OPAT for 39 patients had lower adherence to monitoring recommendations (35.9% vs 68.3%, P = .003). No difference could be detected in achievement of goal vancomycin and aminoglycoside serum concentrations for the 14 cases and 19 controls requiring therapeutic drug monitoring (57.1% vs 68.4%, respectively, P = .765). Seven patients were enrolled in the study after pharmacy monitoring was implemented. Adherence to monitoring recommendations for these patients was significantly improved compared to the prior patients who lacked ID physician supervision (35.9% vs 100%, P = .0065). CONCLUSION: Non-ID physicians are less likely to monitor OPAT according to the IDSA guidelines than ID physicians; however, pharmacist oversight improves adherence to recommendations. Further studies of monitoring of OPAT by pharmacists should investigate the impact of pharmacist involvement on prevention of adverse events and hospital readmissions.

Evaluating the appropriate use of piperacillin/tazobactam in a community health system: a retrospective chart review.

Noting inappropriate uses of piperacillin/tazobactam at their institution, the authors emphasize the need for antimicrobial stewardship efforts, as well as infection-control practices, to curtail drug resistance, reduce costs, and minimize adverse events.