Interest in Home Birth During the COVID-19 Pandemic: Analysis of Google Trends Data.

INTRODUCTION: Nearly all (94%-99%) pregnant persons in developed countries search for pregnancy-related information online. The advent of the novel coronavirus disease 2019 (COVID-19) and the associated restrictions in hospital policies may have pushed pregnant persons in the United States to consider giving birth at home to achieve their desired birth experience. METHODS: Google Trends is an open, rich source of real-time, anonymized, relative data on disease patterns and population behavior that provides data in the form of search volume index (SVI): the search volume for a queried term relative to overall search volume for a given time frame and geographic location. The SVI is normalized to a scale of 0 to 100. After the World Health Organization declared COVID-19 a pandemic on March 11, 2020, Google Trends was queried on February 21, 2021, for the search term home birth with location set to the United States and the time frame March 11, 2019 to February 21, 2021. RESULTS: The median SVI for home birth during nominally pre-COVID-19 baseline (weeks of March 17, 2019 to March 8, 2020) was relatively constant at 43 (range, 25-56) and increased sharply to 77 during the week of March 15, to 86 during the week of March 22, and peaked at 100 during the week of March 29, 2020. The SVI declined substantially in the following weeks but remained significantly elevated compared with baseline levels. During the approximate 2-year period of query, the states with the highest SVI values (≥80) were Arkansas, Washington, Montana, and Georgia. DISCUSSION: Interest in home birth spiked in the United States immediately after COVID-19 was declared a pandemic and remained significantly elevated thereafter. These results have implications for caregivers and health systems to ensure safe pregnancies and childbirths through the resolution of the ongoing pandemic.

Comparison of the bacterial etiology of early-onset and late-onset ventilator-associated pneumonia in subjects enrolled in 2 large clinical studies.

BACKGROUND: Ventilator-associated pneumonia (VAP) is classified as early-onset or late-onset, in part, to identify subjects at risk for infection with resistant pathogens. We assessed differences in the bacterial etiology of early-onset versus late-onset VAP. METHODS: Subjects enrolled in 2004-2006 in 2 clinical studies of doripenem versus imipenem or piperacillin/tazobactam, with a diagnosis of VAP (n = 500) were included in the analysis. Subjects were classified by ventilator status: early-onset VAP (< 5 d of ventilation) or late-onset VAP (≥ 5 d of ventilation). Baseline demographics and bacterial etiology were analyzed by VAP status. RESULTS: Late-onset VAP subjects had higher Acute Physiology and Chronic Health Evaluation (APACHE II) scores (mean 16.6 versus 15.5, P = .008). There were no significant differences in Clinical Pulmonary Infection Score, sex, age, or presence of bacteremia between the groups. A total of 496 subjects had a baseline pathogen, and 50% of subjects in each group had ≥ 2 pathogens. With the exception of Staphylococcus aureus, which was common in early-onset VAP, the pathogens (including potentially multidrug-resistant (MDR) pathogens) isolated from early-onset versus late-onset VAP were not significantly different between groups. Acinetobacter baumannii or Pseudomonas aeruginosa with decreased susceptibility to any study drug was observed in early-onset and late-onset VAP subjects. CONCLUSIONS: There were no significant differences in the prevalence of potential MDR pathogens associated with early-onset or late-onset VAP, even in subjects with prior antibiotics. Empiric therapy for early-onset VAP should also include agents likely to be effective for potential MDR pathogens. Further prospective studies should evaluate microbiology trends in subjects with VAP.

Extended-release/long-acting opioid REMS may fill the need for prescribers' appropriate use education.

The Food and Drug Administration (FDA) is requiring manufacturers of long-acting and extended-release opioids to have a class-wide Risk Evaluation and Mitigation Strategy (REMS). The comprehensive risk management plan will include training for prescribers on the appropriate and safe use of these pain medications. The letter dated April 19, 2011 from FDA to manufacturers outlining the REMS requirements describes voluntary training that should be certified education "where practicable." The current report includes data from a recent comprehensive study of healthcare professionals and patients and highlights key insights that can guide the development of the opioid REMS training.

A randomised, double-blind trial comparing ceftobiprole medocaril with ceftriaxone with or without linezolid for the treatment of patients with community-acquired pneumonia requiring hospitalisation.

Community-acquired pneumonia (CAP) is a serious infection requiring hospitalisation in 20% of cases. The novel cephalosporin ceftobiprole has microbiological activity against the major bacterial pathogens causing CAP, including Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae, as well as against Staphylococcus aureus, including meticillin-resistant S. aureus (MRSA). This was a multicentre, double-blind study in which 706 patients with CAP severe enough to require hospitalisation were randomised to ceftobiprole or to an expert-recommended course of ceftriaxone ± linezolid (comparator group). Clinical and microbiological outcomes were determined 7-14 days after completion of therapy (test-of-cure visit). For the 469 clinically evaluable patients, cure rates were 86.6% vs. 87.4% for ceftobiprole and comparator, respectively [95% confidence interval (CI) of the difference, -6.9% to 5.3%]; in the intention-to-treat (ITT) analysis of 638 CAP patients, these cure rates were 76.4% vs. 79.3%, respectively (95% CI of the difference, -9.3% to 3.6%). A typical bacterial pathogen was identified in 29% of the ITT population. Microbiological eradication rates in the 144 microbiologically evaluable patients were 88.2% and 90.8% for the respective treatment groups (95% CI of the difference, -12.6% to 7.5%). Both study drugs were well tolerated, with but a minority of patients requiring premature discontinuation due to an adverse event (6% in the ceftobiprole group and 4% in the comparator group). The overall incidence of treatment-related adverse events was higher in the ceftobiprole group, primarily owing to differences in rates of self-limited nausea (7% vs. 2%) and vomiting (5% vs. 2%). In summary, ceftobiprole was non-inferior to the comparator (ceftriaxone ± linezolid) in all clinical and microbiological analyses conducted, suggesting that ceftobiprole has a potential role in treating hospitalised patients with CAP. [ClinicalTrials.gov identifier: NCT00326287].

Risk evaluation and mitigation strategies (REMS): educating the prescriber.

The US FDA Amendments Act of 2007 was signed into law on 27 September 2007. A provision of this law granted the FDA new powers to enhance drug safety by requiring the pharmaceutical industry to develop Risk Evaluation and Mitigation Strategies (REMS). REMS are deemed necessary when a question exists as to whether the benefits of a drug outweigh its risks. REMS constitute a safety plan with several potential components, including a medication guide, a communication plan, elements to ensure safe use and an implementation system to help guide the prescribers, pharmacists and patients. This applies to existing drugs on the market, new drug applications (NDAs), abbreviated NDAs (generics) and biologics licence applications. REMS represent an 'upgrade' from previously required risk minimization action plans, based on the strengthening of FDA powers of authority and enforceability to incur monetary penalties against individuals representing the pharmaceutical industry who fail to comply. For illustrative purposes, we chose the drug romiplostim (Nplate®) to present an REMS, as all components were utilized to help assuage risks associated with the drug. Romiplostim is an FDA-approved drug used to treat thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura that has a significant adverse safety profile based on the risk of changes in bone marrow reticulin formation and bone marrow fibroses, and other associated risks. This review of current REMS policy is intended to provide the prescriber with a better understanding of current modalities in FDA-mandated drug safety programmes, which will impact day-to-day healthcare provider practices.

Safety and efficacy of levofloxacin 750 mg for 2 weeks or 3 weeks compared with levofloxacin 500 mg for 4 weeks in treating chronic bacterial prostatitis.

OBJECTIVE: To compare the safety and efficacy of levofloxacin 750 mg QD for 2 weeks or levofloxacin 750 mg QD for 3 weeks to levofloxacin 500 mg QD for 4 weeks in treating chronic bacterial prostatitis (CBP). RESEARCH DESIGN AND METHODS: This was a randomized, multicenter, double-blind, noninferiority study. The primary efficacy end point was investigator assessment of clinical success in the modified intent-to-treat (mITT) population at post-therapy. National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) scores were utilized to evaluate subject-reported responses post-therapy. RESULTS: A total of 241 subjects were enrolled. At post-therapy (test of cure [TOC]), clinical success rates for levofloxacin-treated subjects (750 mg QD for 3 weeks [64.9%, 48/74]) were noninferior to 500 mg QD for 4 weeks (69.3%, 52/75: 95% CI, -19.5%, 10.6%). Success rates with levofloxacin 750 mg QD for 2 weeks (63.0%, 46/73) were not noninferior to therapy with levofloxacin 500 mg QD for 4 weeks (95% CI, -21.5%, 8.9%) at TOC. At 3 and 6 months post-therapy, clinical success rates were clinically higher for the 500-mg, 4-week treatment group, and statistical analysis demonstrated both groups were not noninferior to standard therapy with levofloxacin 500 mg (95% CI, -32.5%, -0.6% for both 750-mg groups at 6 months). NIH-CPSI scores showed similar trends. Overall, adverse event (AE) rates were similar for the three treatment groups; however, discontinuation of therapy due to AEs was higher with the 750-mg dose (p = 0.02, and p = 0.13 for 750 mg, 2 weeks and 750 mg, 3 weeks versus 500 mg for 4 weeks, respectively). The main limitation of this study was that no bacterial cultures were required. CONCLUSIONS: Higher doses for shorter durations were determined to be no worse than standard therapy with levofloxacin 500 mg for a longer duration at the TOC visit. However, at the 6-month follow-up visit, the levofloxacin 750-mg dose administered for either 2 weeks or 3 weeks was inferior to the standard therapy, suggesting that a longer duration of treatment may help extend the relapse-free interval in patients with CBP. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, nct00402688.

Meta-analysis of doripenem vs comparators in patients with pseudomonas infections enrolled in four phase III efficacy and safety clinical trials.

OBJECTIVE: Pseudomonas aeruginosa is a difficult-to-treat bacterial pathogen often isolated from patients with serious nosocomial infections. The goal of this analysis is to present the clinical and microbiologic effectiveness of doripenem in the treatment of infections due to P. aeruginosa. RESEARCH DESIGN AND METHODS: A meta-analysis was conducted on the subset of subjects enrolled in four randomized phase III clinical trials of doripenem in subjects with complicated intra-abdominal infections (cIAI) and nosocomial pneumonia/ventilator-associated pneumonia (NP/VAP) due to P. aeruginosa. Clinical and microbiologic success was determined by infection and across the two infections. RESULTS: Clinical success rates for modified intent-to-treat (mITT) subjects with P. aeruginosa in the cIAI and NP/VAP groups were 78.7% (37/47) and 59.6% (31/52), respectively, following treatment with doripenem versus 74.3% (26/35) and 32.8% (19/58), respectively, for subjects in the comparator groups (p < 0.05 for difference in success rates across infection types). Microbiologic eradication rates also favored doripenem, although the differences did not achieve statistical significance. The weighted difference (doripenem minus comparator) for the mITT population in clinical success rates between doripenem and the comparator agents was 16.0% (95% CI: 3.1%, 29.0%) and for microbiologic eradication rates was 9.1% (95% CI: -4.2%, 22.3%). The proportion of subjects reporting one or more treatment-emergent adverse events or serious adverse events was similar for doripenem and the comparator agents. Fourteen doripenem and 14 comparator subjects died during the study. Limitations of this retrospective meta-analysis also include the qualitative heterogeneity of the data, and a selected, narrow population of moderately ill clinical trial subjects included in the analysis. Due to limitations, these data may not be generalizable to all populations and should be considered hypothesis generating. CONCLUSION: The weighted difference in clinical success rates for subjects with cIAI and NP/VAP infections caused by P. aeruginosa was in favor of doripenem, with the relative benefit of doripenem compared with the comparator agents similar across the two infections.

Oral gatifloxacin in outpatient community-acquired pneumonia: results from TeqCES, a community-based, open-label, multicenter study.

Gatifloxacin is an 8-methoxy fluoroquinolone with broad activity against respiratory tract pathogens, including those commonly associated with community-acquired pneumonia (CAP). To evaluate the efficacy and safety of oral gatifloxacin 400 mg once daily for seven to 14 days, community-based physicians enrolled adult outpatients with confirmed or suspected CAP in a prospective, single-arm, open-label, noncomparative study. Of 1488 clinically evaluable patients with radiographically confirmed or clinically suspected CAP, 1417 (95.2%) were cured. All strains of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, the most commonly isolated pathogens, were susceptible to gatifloxacin. Penicillin nonsusceptibility was seen in 32.6% of S. pneumoniae isolates, and beta-lactamase production was detected in H. influenzae (26.9%) and M. catarrhalis (88%) isolates. Clinical cure rates of 91%, 94%, and 92% were achieved in patients with S. pneumoniae, H. influenzae, and M. catarrhalis, respectively. All seven patients with fully penicillin-resistant S. pneumoniae (MIC > or =2 micro g/ml) were cured. Gatifloxacin was well tolerated, with the most common drug-related adverse events being nausea (2.8%) and diarrhea (1.7%). Gatifloxacin is effective and well tolerated as empiric therapy for CAP in the outpatient community setting.

Gatifloxacin used for therapy of outpatient community-acquired pneumonia caused by Streptococcus pneumoniae.

Gatifloxacin is an advanced-generation fluoroquinolone with demonstrated efficacy and safety as therapy for community-acquired pneumonia (CAP). As part of a phase IV postmarketing surveillance program (TeqCES), 136 outpatients with CAP whose sputum was culture-positive for Streptococcus pneumoniae were enrolled in an open-label trial of oral gatifloxacin 400 mg daily for 7 to 14 days. An antibiogram of isolates showed 100% susceptibility to gatifloxacin (MIC(90) 0.5 micro g/mL) and respective susceptibilities of 67%, 70%, and 80% to penicillin, erythromycin, and tetracycline. Clinical cure was achieved in 95.3% of evaluable patients, including seven patients infected with penicillin-resistant S. pneumoniae (MIC > or =2 micro g/mL). The bacteriologic eradication rate for S. pneumoniae was 94.5%. Diarrhea, nausea, and dizziness, the most common adverse events in CAP patients (<3%), were generally mild to moderate; no serious adverse events were recorded. These results support recommendations to treat CAP, particularly due to S. pneumoniae including multidrug-resistant strains, with the newer 8-methoxy-fluoroquinolone, gatifloxacin.

Haemophilus influenzae in respiratory tract infections in community-based clinical practice: therapy with gatifloxacin.

In this community-based safety surveillance study, the advanced-generation fluoroquinolone gatifloxacin was administered empirically to 15625 adults with community-acquired respiratory tract infections (RTIs), including 1562 clinically evaluable patients with community-acquired pneumonia (CAP) and 2391 with acute exacerbations of chronic bronchitis (AECB). Haemophilus influenzae was the most common pathogen isolated in AECB (40.1%) and the second most common in CAP (36.8%). In vitro susceptibility to gatifloxacin and other fluoroquinolones, amoxicillin/clavulanate, ceftriaxone, cefuroxime axetil, tetracycline, and azithromycin ranged from 95.8% to 100%. In comparison, a significant percentage of the isolates were not susceptible to clarithromycin ( approximately 41%), ampicillin (22% to 28%), and trimethoprim/sulfamethoxazole (14% to 18%). The susceptibility pattern was generally independent of exposure to another antimicrobial in the previous 30 days. CAP and AECB patients infected with H. influenzae had signs and symptoms similar to those infected with Streptococcus pneumoniae. Among clinically evaluable patients with H. influenzae, gatifloxacin cured 159 of 166 (95.8%) with AECB and 112 of 118 (94.9%) with CAP. The cure rate was independent of the beta-lactamase status or serotype of the H. influenzae strain. H. influenzae is not a more benign pathogen in community-acquired RTIs but causes signs and symptoms that are indistinguishable from those caused by other pathogens, notably S. pneumoniae.

Gatifloxacin in community-based treatment of acute respiratory tract infections in the elderly.

The elderly are at increased risk for respiratory tract infections. To evaluate the safety and efficacy of gatifloxacin in adults of any age with community-acquired respiratory tract infections, this open-label, multicenter, noncomparative study in community-based practices enrolled male and female outpatients at least 18 years old with a clinical diagnosis of community-acquired pneumonia (CAP), acute-bacterial exacerbation of chronic bronchitis (AECB), or acute uncomplicated maxillary sinusitis. Gatifloxacin 400 mg was administered once daily for seven to 14 days. Of 14781 clinically evaluable patients, 2505 were at least 65 years old, 499, at lest 80. Cure rates for CAP, AECB, and sinusitis ranged from 91.6% to 95.5% for patients less than 65 years old, 91.1% to 96.2% for those 65 to 79 years of age, and 89.5% to 94.8% for those at least 80 years old. Each age group, including patients with concomitant cardiovascular or diabetic conditions, tolerated treatment well. Gatifloxacin is efficacious and well tolerated in adult outpatients of any age with respiratory tract infections and is an important therapeutic option, particularly in communities with a high prevalence of resistant pathogens.

Efficacy and safety of gatifloxacin in elderly outpatients with community-acquired pneumonia.

To evaluate the safety and efficacy of gatifloxacin in adults <65, 65 to 79, or > or =80 years old with community-acquired pneumonia, adult male and female outpatients from general community-based practices were enrolled in an open-label, multicenter, noncomparative study. Gatifloxacin 400 mg once daily was administered for seven to 14 days. Medical history, physical examination, signs and symptoms of infection, Gram stain and culture if specimen available, clinical response, and safety were determined. Of 1655 treated patients, 1103 were at least 65 years old, 405 were 65 to 79, and 147 were at least 80. Patients > or =80 years old presented with chills, chest pain, fever, or headache less often than younger patients. Cure rates were 95.5% for patients <65 years old, 96.2% for those 65 to 79, and 90.2% for those at least 80 years old. Neither the frequency nor susceptibility of isolated pathogens appeared to differ with age. Between 93.7% and 100% of subsets of the two younger groups with verified Streptococcus pneumoniae or Hemophilus influenzae were cured. All oldest-group patients in the subset with verified S. pneumoniae and 71.4% (7) of patients with H. influenzae were cured. Each age group, including current or past smokers and patients receiving medications for concomitant conditions, tolerated treatment well. Gatifloxacin is safe and efficacious in adults of any age with community-acquired pneumonia, including the elderly up to 100 years old and patients with S. pneumoniae including penicillin-resistant strains.

Community-based treatment of acute uncomplicated bacterial rhinosinusitis with gatifloxacin.

OBJECTIVE: We sought to evaluate gatifloxacin in adults with acute uncomplicated bacterial rhinosinusitis. STUDY DESIGN: TeqCES was an open-label, multicenter, noncomparative study of the safety and efficacy of gatifloxacin. More than 11,000 adult patients with acute uncomplicated rhinosinusitis received gatifloxacin 400 mg once daily for 10 days. RESULTS: Moraxella catarrhalis (91% beta-lactamase producers), Haemophilus influenzae (28% beta-lactamase producers), Streptococcus pneumoniae (18% intermediately resistant and 14% fully resistant to penicillin), and Staphylococcus aureus were the predominant pathogens isolated from purulent nasal discharge. More than 99% of rhinosinusitis pathogens isolated from the nasopharynx of patients meeting the clinical criteria for rhinosinusitis were susceptible to gatifloxacin. Among 10,353 patients whose clinical response could be determined, 91.6% were cured. Clinical cure rates exceeded 90% for the major pathogens. Gatifloxacin was well tolerated; drug-related adverse events that occurred in 1% or more of patients were nausea (4.4%), dizziness (1.8%), diarrhea (1.4%), and headache (1.0%). CONCLUSION: Gatifloxacin is effective for patients with acute bacterial rhinosinusitis in the community.

Efficacy and tolerability of gatifloxacin in community treatment of acute exacerbations of chronic bronchitis.

BACKGROUND: Recognizing acute exacerbations of chronic bronchitis (AECB) and selecting appropriate antibiotic treatment for patients who would benefit most is a challenge for community-based physicians. OBJECTIVE: The Tequin Clinical Experience Study, an open-label, noncomparative, postmarketing trial, assessed the efficacy and tolerability of gatifloxacin, an 8-methoxy fluoroquinolone, in the treatment of AECB in the community-practice setting. METHODS: Consecutive patients with respiratory tract infections in community-based settings were eligible for participation. Treated patients (N = 2512) included 1107 men (44.1%) and 1405 women (55.9%) aged > or =18 years with a clinical diagnosis of chronic bronchitis. All participants received oral gatifloxacin 400 mg once daily for 7 to 10 days. Clinical response was determined via telephone contact conducted by the investigator or study coordinator using case-report forms or during an office visit after the last dose. The investigator or coordinator collected expectorated or induced sputum specimens that were then smeared on a microscope slide, stored in a tube, and transported to a central reference laboratory for Gram-staining and culture. Of 1388 pretreatment sputum specimens submitted, pathogens were isolated from 424. RESULTS: The most frequently detected pathogens were Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. All H. influenzae and 99% of S. pneumoniae isolates tested were susceptible to gatifloxacin. Of the 2267 patients with a determinable clinical response, 2084 (91.9% [95% CI, 90.8%-93.0%]) were cured (all acute symptoms improved or returned to baseline level, no new symptoms present, no additional antibiotic required). The 95.8% cure rate in 166 patients with H. influenzae included 100% of those with beta-lactamase-positive strains. Overall, 89.2% of 111 patients with M. catarrhalis were cured; rates were similar regardless of beta-lactamase production. The clinical cure rate in 74 patients with S. pneumoniae was 98.6% and was independent of the degree of penicillin resistance (minimum inhibitory concentration > or =2.0 microg/ mL). All 6 patients infected with S. pneumoniae fully resistant to penicillin were cured. Gatifloxacin was generally well tolerated, and the majority of adverse events were mild to moderate; only 11 drug-related adverse events in 10 patients (0.4%) were serious. Drug-related nausea (3.0%), dizziness (1.5%), diarrhea (1.2%), and vomiting (0.9%) were the most common adverse events. CONCLUSIONS: The high clinical cure rate and favorable tolerability support gatifloxacin as a rational choice for the treatment of AECB in patients such as those in this community-based study.

Antimicrobial-associated acute hepatitis.

Recently, the case history of a 44-year-old woman who experienced acute hepatitis subsequent to therapy for chronic sinusitis was reviewed. The patient sequentially was administered clarithromycin, levofloxacin, amoxicillin-clavulanate, and gatifloxacin. Her adverse events were attributed definitively to gatifloxacin, a surprising conclusion because many other possible causes of hepatitis existed in this case. Not ruled out as potential causes of the clinical and laboratory adverse events were hepatitis other than hepatitis A or B. Other antimicrobials administered were dismissed. In particular, extended treatment with amoxicillin-clavulanate has been clearly linked to hepatotoxic effects that may occur long after therapy begins. Thus, while we agree that physicians must be aware of the potential for antimicrobial hepatotoxicity, we believe that this case study is not a solidly documented case of hepatitis attributable to gatifloxacin and overlooks other possible causes of acute hepatitis of which prescribers should be aware.