Less common bacterial, fungal and viral infections: review of management in the pregnant patient.

This review is a comprehensive summary of treatment options for pregnant patients with less common bacterial, fungal, and viral infections. It offers guidance to clinicians based on the most recently published evidence-based research and expert recommendations. A search of MEDLINE (inception to March 2021) and the CDC website was performed. Liposomal amphotericin B is the preferred therapy for cryptococcosis, histoplasmosis, oesophageal candidiasis, and coccidioidomycosis, especially during the first trimester due to teratogenic concerns with azole antifungals. For oral candidiasis, clotrimazole troches or miconazole mucoadhesive buccal tablets are recommended. A ß-lactam antimicrobial is preferred over doxycycline for various manifestations of Lyme disease and the drug of choice for Pneumocystis pneumonia is trimethoprim/sulfamethoxazole. Acyclovir is the preferred antiviral for varicella zoster virus. Fluoroquinolones, macrolides, and aminoglycosides should be avoided if possible and there are alternate agents available for an effective treatment regimen. There is a scarcity of clinical data in pregnant patients with less common bacterial, fungal and viral infections. This population lacks definitive recommendations in many clinical practice guidelines. The key to optimizing therapy is a comprehensive review of the available evidence and a careful balance of risks and benefits before final treatment decisions.

Use of continuous-infusion ceftolozane/tazobactam for resistant Gram-negative bacterial infections: a retrospective analysis and brief review of the literature.

Ceftolozane/tazobactam (C/T), a novel antipseudomonal cephalosporin plus ß-lactamase inhibitor, is used in multidrug-resistant Gram-negative infections. Continuous infusion (CI) of C/T is an attractive concept for aiding in transitions of care and maximising the pharmacodynamics of cephalosporins (T>MIC). This was a single-centre retrospective analysis of CI C/T use in adults from December 2016 to June 2019 in the inpatient or outpatient setting. Safety and effectiveness were assessed. When therapeutic drug monitoring (TDM) was performed, area under the concentration-time curve (AUC) and target attainment were calculated. Summary statistics were used to describe the data. CI C/T was used in seven unique regimens over the 31-month evaluation period. Patient age ranged from 23-70 years and the indication was primarily for treatment of deep-seated infections caused by multidrug-resistant Pseudomonas aeruginosa. Four regimens (57%) were used for outpatient transitions of care. The typical dose was 6 g every 24 h, although a renally adjusted dose was used in two instances (29%). TDM was performed in four uses (57%) and target attainment was confirmed in each. Ceftolozane AUC ranged from 365.7-818.2 µg•(h/mL). All patients had positive outcomes with no significant adverse events. One patient developed acute gout flares. One patient had recurrent infection with C/T-resistant P. aeruginosa after ~3 months of reduced dose for suppression. CI C/T was successfully utilised for deep-seated infections in inpatient and outpatient settings. TDM confirmed that CI C/T achieved pharmacodynamic targets for the entire dosing interval, suggesting an effective alternative dosing regimen applicable across the continuum of care.

Empirical fluoroquinolones versus broad-spectrum beta-lactams for Gram-negative bloodstream infections in the absence of antimicrobial resistance risk factors.

OBJECTIVES: Increasing antimicrobial resistance rates limit empirical antimicrobial treatment options for Gram-negative bloodstream infections (GN-BSI). However, antimicrobial resistance may be predicted based on patient-specific risk factors using precision medicine concepts. This retrospective, 1:2 matched cohort examined clinical outcomes in hospitalized adults without major risk factors for antimicrobial resistance receiving empirical fluoroquinolones or broad-spectrum beta-lactams (BSBL) for GN-BSI at Prisma Health-Midlands hospitals in Columbia, SC, USA from January 2010 through June 2015. METHODS: Multivariable logistic regression was used to examine early treatment failure at 72-96 h from GN-BSI. Cox proportional hazards regression was used to examine 28-day mortality and hospital length of stay (HLOS). RESULTS: Among 74 and 148 patients receiving empirical fluoroquinolones and BSBL for GN-BSI, respectively, median age was 68 years, 159 (72%) were women, and 152 (68%) had a urinary source of infection. Early treatment failure rates were comparable in fluoroquinolone and BSBL groups (27% vs. 30%, respectively, odds ratio 0.82, 95% confidence intervals [CI] 0.43-1.54, P = 0.53), as well as 28-day mortality (8.9% vs. 9.7%, respectively, hazards ratio [HR] 0.74, 95% CI 0.26-1.90, P = 0.54). Median HLOS was 6.1 days in the fluoroquinolone group and 7.1 days in the BSBL group (HR 0.73, 95% CI 0.54-0.99, P = 0.04). Transition from intravenous to oral therapy occurred sooner in the fluoroquinolone group than in the BSBL group (3.0 vs. 4.9 days, P < 0.001). CONCLUSIONS: In the absence of antimicrobial resistance risk factors, fluoroquinolones provide an additional empirical treatment option to BSBL for GN-BSI. Shorter HLOS in the fluoroquinolone group may be due to earlier transition from intravenous to oral antimicrobial therapy.

Use of continuous infusion ceftolozane-tazobactam with therapeutic drug monitoring in a patient with cystic fibrosis.

PURPOSE: The safe and effective use of ceftolozane-tazobactam delivered via continuous infusion in a cystic fibrosis (CF) patient with reduced body weight and presumed augmented renal clearance is reported. SUMMARY: A 30-year-old woman with CF was admitted for acute pulmonary exacerbations with positive respiratory cultures for Pseudomonas aeruginosa and extended-spectrum ß-lactamase-producing Escherichia coli. Susceptibility testing confirmed multidrug resistance, and the patient was transitioned to ceftolozane-tazobactam for definitive therapy. A novel strategy of administering ceftolozane-tazobactam 6 g by continuous i.v. infusion over 24 hours was initiated during hospitalization and continued at discharge for a total of 10 days. Therapeutic drug monitoring over the first 36 hours of the continuous infusion confirmed adequate exposure. The patient had clinical resolution with return to baseline of pulmonary function tests and no noted adverse drug events. CONCLUSION: A continuous infusion regimen of ceftolozane-tazobactam was successfully used in a CF patient with augmented renal clearance.

Restriction-free antimicrobial stewardship initiative targeting fluoroquinolone reduction across a regional health-system.

BACKGROUND: Fluoroquinolone (FQ) antibiotics have become a target of many antimicrobial stewardship programmes. Multiple post-marketing warnings from the Food and Drug Administration caution against use of this drug class for certain infections due to risk of harmful adverse effects outweighing benefit. Commonly employed strategies to affect antibiotic prescribing can be restrictive and without improvement in overall antibiotic appropriateness or decrease in collateral damage. AIM: To develop a strategy for sustainable optimization of FQ antibiotics. SETTING: Multi-state health-system of 14 hospitals and medical centers. METHODS: The health-system antimicrobial stewardship program identified the opportunity to improve FQ utilization. In collaboration with our data and analytics team, specific targets of FQ use in pneumonia and chronic obstructive pulmonary disease were established. Face-to-face provider education and prospective audit and feedback were the mainstays of the campaign. Enhancements to the electronic medical record to support the initiative were also implemented. FINDINGS: There was an overall decrease in FQ utilization by 56.9%. For pneumonia use of FQs decreased from 16.4% to 8.1% and in COPD changed from 29.6% to 9.7% over the same time period. CONCLUSIONS: A non-restrictive FQ optimization initiative based on education and feedback decreased both FQ consumption and total antibiotic use across a large multi-hospital health-system.

Common Bacterial and Viral Infections: Review of Management in the Pregnant Patient.

OBJECTIVE: To review the treatment of common bacterial and viral infections occurring in the pregnant patient. DATA SOURCES: A literature search of MEDLINE was performed (inception to October 2018). The Centers for Disease Control and Prevention website was utilized for additional information. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language studies and those conducted in humans were considered. DATA SYNTHESIS: ß-Lactams alone or in combination are the preferred treatment for many common infections in pregnancy, such as urinary tract infections, pelvic inflammatory disease (PID), gonococcal infections, syphilis, chancroid, upper- and lower-respiratory-tract infections, certain gastrointestinal infections, Group B Streptococcus, listeriosis, and intrauterine inflammation or infection. Macrolides, particularly azithromycin, are also utilized for the treatment of PID, chlamydia, gonococcal infections, chancroid, community-acquired pneumonia, and certain gastrointestinal infections. Other antibiotics or antivirals such as vancomycin, aminoglycosides, metronidazole, nitrofurantoin, fosfomycin, acyclovir, valacyclovir, and oseltamivir are included in the preferred therapy for some common bacterial and viral infections in pregnant patients as well. Relevance to Patient Care and Clinical Practice: This review synthesizes available evidence of treatments of common infections in pregnancy and provides a concise summary to guide clinicians on empirical treatment during pregnancy. CONCLUSIONS: There are limited data on clinical outcomes in pregnant patients with common bacterial and viral infections. Empirical management decisions require balance of benefit and risk to both mother and infant. Although few clinical practice guidelines have quality evidence for strong recommendations in this population, clinicians should weigh antimicrobial dosing, pharmacokinetics, safety, and established effectiveness to optimize antimicrobial therapy in pregnancy.