Empiric Therapy Of Community-acquired Pneumonia Research Articles

Analysis of antibacterials for systemic use recommended for the treatment of patients with community-acquired pneumonia in Ukraine according to the modern approach to preventing the development of antimicrobial resistance

BACKGROUND. According to a 2019 epidemiological study, antibiotic resistance (AR) caused about 1.27 million deaths worldwide, with lower respiratory tract infections (particularly pneumonia) dominating the global disease burden caused by resistant microorganisms.
 OBJECTIVE. To determine the compliance of antibiotics (J01), which are recommended by the guidelines of the National Academy of Medical Sciences of Ukraine for the empiric therapy of community-acquired pneumonia (CAP) in adults, with World Health Organization (WHO) recommendations based on the prevention of the development of AR.
 MATERIALS AND METHODS. Objects – antibiotics (J01) recommended by the guideline and their belonging to the access, watch and reserve groups according to the WHO AWaRe classification of antibiotics. Methods: system overview, analytical, comparison and generalization.
 RESULTS AND DISCUSSION. In the guidelines for empiric therapy of CAP in adults, antibiotics of 7 groups are recommended, from which 36 international non-proprietary names (INNs) were selected and analyzed. Of these, 7 INNs belong to the access group, of which only 4 antibiotics (amoxicillin, amoxicillin / clavulanic acid, gentamicin, doxycycline) are recommended by WHO experts for empiric treatment of CAP in adults; 26 INNs belong to the watch group, but only 3 antibiotics (cefotaxime, ceftriaxone, clarithromycin) according to the WHO database are recommended as empiric therapy for the severe CAP in adults. Ceftaroline, according to the WHO AWaRe antibiotic classification, belongs to the reserve group and should be used to fight multiresistant microorganisms. No antibiotic of the reserve group is recommended by WHO for empiric therapy of CAP.
 CONCLUSIONS. The results of the analysis can be used in updating the recommendations for rational empiric antibiotic therapy of CAP, taking into account the mechanisms of resistance to the development and spread of AR.

Evaluation of the Efficacy and Safety of Initial Empirical Antibiotic Therapy for Community-Acquired Pneumonia in Middle-Aged People

β-lactam antibiotics, including cephalosporins, are the drugs of choice for empirical antibiotic therapy (ABT) in patients with community-acquired pneumonia. Unreasonable and irrational use of antibiotics leads to an increased risk of adverse reactions, contributes to the growth of antibiotic resistance.The aim of the study was to analyse data on the efficacy and safety of initial empirical ABT using cephalosporins for community-acquired pneumonia in middle-aged patients of multidisciplinary hospitals in Moscow.Materials and methods: the authors analysed 177 archived medical records of the patients admitted to three multidisciplinary hospitals (I.V. Davydovsky City Clinical Hospital, City Clinical Hospital 52 and City Clinical Hospital 4) in Moscow from 2017 to 2019 and prescribed mono- and/or combination therapy including a cephalosporin antibiotic as a starting therapy for community-acquired pneumonia. The initial ABT was considered effective if a patient’s body temperature normalised within 48–72 h following initiation of treatment and safe if no adverse reactions developed during the period of inpatient treatment.Results: the combination of ceftriaxone and azithromycin was the most frequently prescribed ABT regimen; its effectiveness was 71.9%. Ceftriaxone monotherapy was the second in frequency of prescription; its effectiveness amounted to 77.2%. The third regimen included cefotaxime and azithromycin and was effective in 70% of cases. The patients who needed a change in initial ABT had a significantly higher incidence of developing severe community-acquired pneumonia and complications. The study results indicate that the structure of comorbidity did not affect the effectiveness of initial empirical ABT. Streptococcus pneumoniae was found to be the most common causative agent of community-acquired pneumonia in the studied population (44.8% of cases). Only 13% of the patients faced adverse reactions associated with the use of antibiotics as part of the initial empirical ABT; the most common were leukopenia and diarrhoea.Сonclusions: the results of the study indicate the feasibility of mono- and/or combination ABT including a cephalosporin antibiotic as a starting empirical therapy for community-acquired pneumonia due to its effectiveness and favourable safety profile.

Evaluation of the Effect of Comorbidity on the Efficacy and Safety of β-Lactam Antibiotics in Patients with Community-Acquired Pneumonia

Lower respiratory tract infections, which include community-acquired pneumonia (CAP), are the most common cause of death among all infectious diseases. The presence of a comorbid pathology in a patient with CAP suggests a possibility of mutual influence and changes in the course of both the underlying disease and comorbidities, as well as changes in the effectiveness and safety of ongoing drug therapy. The aim of the study was to analyse literature data on the structure of comorbidity in CAP patients and its impact on the efficacy and safety of therapy with β-lactam antibiotics. It has been established that CAP most often occurs in patients with chronic obstructive pulmonary disease, cardiovascular diseases (ischemic heart disease, arterial hypertension, and chronic heart failure), cerebrovascular disease, chronic kidney disease, diabetes mellitus, bronchial asthma, leukemia, anemia, dementia, neurological disorders, and cancer. The most common causative agent of CAP, regardless of the patient’s age and comorbidity, is pneumococcus (Streptococcus pneumoniae), followed by intracellular pathogens (mycoplasmas, chlamydia) and Haemophilus influenzae, as well as respiratory viruses. With this in mind, the initial empiric therapy for CAP mainly includes β-lactam antibiotics, which are effective against pneumococcus. If patients with CAP have concomitant chronic diseases and conditions, the spectrum of pneumonia pathogens may differ from that in the general population and include rare pathogens and multidrug-resistant strains. The effectiveness of antibiotic therapy in such patients is reduced, which leads to a worsening of the course of both CAP and concomitant diseases. This patient population may require longer treatment with antibiotics, including β-lactams, or the use of antibiotics at doses that provide a higher minimum inhibitory concentration, which is associated with a high risk of adverse reactions and a decrease in the safety of antibiotic therapy.

Pharmacodynamic Evaluation of Ampicillin-sulbactam in Pediatric Patients Using Plasma and Urine Data.

We aimed to develop population pharmacokinetic (PK) models of ampicillin and sulbactam using pooled data analysis and to optimize dosing regimens of ampicillin-sulbactam (combination ratio of 2:1) in pediatric patients. Population PK models of ampicillin and sulbactam were separately developed by simultaneously fitting plasma and urine data from pediatric patients in 14 published studies. Based on these models, we estimated the probability of attaining a pharmacodynamic (PD) target [50% of time that free drug concentrations above the minimum inhibitory concentration, 50% fT > minimum inhibitory concentration (MIC)] against MIC90 [MIC that blocked the growth of 90% of the strains] of common bacteria in community-acquired pneumonia. The analysis included 54 pediatric patients (0.083-16.42 years of age, 4.0-77.0 kg of body weight). A total of 284 plasma concentrations and 90 urinary excretions from 0 to 6 hours after administration were used for population PK modeling. The data were adequately described by 2-compartment models for ampicillin and sulbactam. Age was not a statistically significant covariate in the PK of either drug. The PK/PD breakpoint MICs for 45 mg/kg 3 times daily and 75 mg/kg 4 times daily (q.i.d.) were 0.25 and 1 μg/mL, respectively. For empiric therapy of community-acquired pneumonia, because MIC90 values for the main target pathogens is high (MIC90 = 2 μg/mL for Streptococcus pneumoniae and MIC90 = 4 μg/mL for Haemophilus influenzae), 75 mg/kg q.i.d. (Food and Drug Administration-approved maximum dosage in United States) might be better than 45 mg/kg 3 times daily (within approved dosage in Japan) to cover many pathogens. From the results of this PK/PD approach, 75 mg/kg q.i.d. (Food and Drug Administration-approved maximum dosage) should be recommended in the empiric therapy of community-acquired pneumonia.

Etiology and efficacy of anti-microbial treatment for community-acquired pneumonia in adults requiring hospital admission in Ukraine.

Background and aim:Empiric therapy of community-acquired pneumonia (CAP) remains the standard care and guidelines are mostly based on published data from the United States or Europe. In this study, we determined the bacterial etiology of CAP and evaluated the clinical outcomes under antimicrobial treatment of CAP in Ukraine.Methods:A total of 98 adult subjects with CAP and PORT risk II-IV were recruited for the study. The sputum diagnostic samples were obtained from all patients for causative pathogen identification. Subjects were randomly assigned in a 1:1 ratio to receive delafloxacin 300 mg (n=51) or moxifloxacin 400 mg (n=47) with a blinding placebo. The switch to oral treatment was after a minimum of 6 IV doses according to clinical criteria. The total duration of antibacterial treatment was 5-10 days. In vitro susceptibility of pathogens to delafloxacin and other comparator antibiotics was determined.Results:The most frequently isolated pathogens in adults with CAP were S. pneumoniae – 19.5%, M. pneumoniae – 15.3%, H. influenzae – 13.2%, S. aureus – 10.5%, K. pneumoniae – 10.1%, and H. parainfluenzae – 6.4%. All isolates of S. pneumoniae, S. aureus, M. pneumoniae had sufficient susceptibility to appropriate antibiotics. 9.0% of H. influenzae strains were susceptible to azithromycin. 94.8 % of patients had a successful clinical response to delafloxacin at the end of treatment and 93.9 % – at test-of-cure.Conclusions:In Ukraine, the major bacterial agents that induced CAP in adults were S. pneumoniae, M. pneumoniae, H. influenzae, S. aureus, K. pneumoniae, H. parainfluenzae, E. cloacae, L. pneumophila. Delafloxacin is a promising effective antibiotic for monotherapy of CAP in adults and could be used in cases of antimicrobial-resistant strains. (www.actabiomedica.it)

Beta-Lactam Plus Macrolide for Patients Hospitalized With Community-Acquired Pneumonia: Difference Between Autumn and Spring.

The 2017 Korean guideline on community-acquired pneumonia (CAP) recommended beta-lactam plus macrolide combination therapy for patients hospitalized with severe pneumonia, and beta-lactam monotherapy for mild-to-moderate pneumonia. However, antibiotic treatment regimen for mild-to-moderate CAP has never been evaluated for Korean patients. In this retrospective cohort study, study patients were selected from three evaluation periods (October 1 to December 31, 2014; April 1 to June 30, 2016; October 1 to December 31, 2017) of the National Quality Assessment Program for CAP management and the National Health Insurance data on the selected patients was extracted from 1 year before the first patient enrollment and 1 year after the last patient enrollment at each evaluation period for the analysis of risk adjustment and outcomes. The survival rates between beta-lactam plus macrolide (BM) groups and beta-lactam monotherapy (B) were compared using a Kaplan-Meier survival analysis after propensity score matching by age, gender, confusion, urea, respiratory rate, blood pressure at age of 65 years or older (CURB-65), and Charlson comorbidity index for risk adjustment. The differences between autumn and spring season were also evaluated. A total of 30,053 patients were enrolled. Mean age and the male-to-female ratio were 64.7 ± 18.4 and 14,197:15,856, respectively. After matching, 2,397 patients in each group were analyzed. The 30-day survival rates did not differ between the BM and B groups (97.3% vs. 96.5%, P = 0.081). In patients with CURB-65 ≥ 2, the 30-day survival rate was higher in the BM than in the B group (93.7% vs. 91.0%, P = 0.044). Among patients with CURB-65 ≥ 2, the 30-day survival rate was higher in the BM than in the B group (93.3% vs. 88.5%, P = 0.009) during autumn season, which was not observed during spring (94.2% vs. 94.1%, P = 0.986). Beta-lactam plus macrolide combination therapy shows potential as an empirical therapy for CAP with CURB-65 ≥ 2, especially in autumn.

Combined influence of practice guidelines and prospective audit and feedback stewardship on antimicrobial treatment of community-acquired pneumonia and empyema in children: 2012 to 2016.

Aminopenicillins are recommended empiric therapy for community-acquired pneumonia (CAP). The aim of the study was to assess treatment over a 5-year period after CAP guideline publication and introduction of an antimicrobial stewardship program (ASP). Using ICD-10 discharge codes for pneumonia, children less than 18 years admitted to the Children's Hospital of Eastern Ontario January 1, 2012 and December 31, 2016 were identified. Children ≥ 2 months with consolidation were included. One day of therapy (DOT) was one or more doses of an antimicrobial given for 1 day. Of 1,707 patients identified, 713 met inclusion criteria. Eighteen (2.5%) had bacteria identified by culture and 79 of 265 (29.8%) had Mycoplasma pneumoniae detected. Mean DOT/1,000 patient days of aminopenicillins/penicillin (AAP) increased by 18.1% per year (95% confidence interval [CI] -0.2, 39.9%) and decreased by 37.6% per year (95% CI -56.1, -11.3%) for second- and third-generation cephalosporins in the post-ASP period. The duration of discharge antimicrobials decreased. Of 74 (10.4%) patients who had pleural fluid drained, 35 (47.3%) received more than 5 days of AAP and ≤ 5 days of second-/third-generation cephalosporins with no difference in median length of stay nor mean duration of antimicrobials. Implementation of CAP management guidelines followed by prospective audit and feedback stewardship was associated with a sustained decrease in the use of broad-spectrum antibiotics in childhood CAP. Use of AAP should also be strongly considered in patients with effusions (even if no pathogen is identified), as clinical outcome appears similar to patients treated with broad-spectrum antimicrobials.

Severe community-acquired pneumonia in general medical wards: outcomes and impact of initial antibiotic selection

BackgroundMost international guidelines recommend empirical therapy for community-acquired pneumonia (CAP) to be based on site of care. Some patients with severe CAP are managed in general wards because of limited intensive care unit (ICU) bed or because of unrecognition of the pneumonia severity. Appropriate initial antibiotic treatment for severe CAP outside ICU has not yet been established. This study aimed to determine the prevalence and the impact of initial antibiotic selection on the outcomes of patients with severe CAP who were admitted and managing in general wards.MethodsThis prospective observational study included consecutive patients hospitalized for presumed CAP in general wards over a 1-year period. Severe CAP was identified using the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) criteria. Initial antibiotic treatment in the first 24 h were collected. The primary outcome was the rate of unfavorable outcome (composite outcome of treatment failure and in-hospital death). The secondary outcome was the number of hospital-free days assessed 30 days after enrollment into the study.ResultsThere were 94 patients hospitalized with CAP of which 50 (53.2%) patients were compatible with severe CAP. An etiologic diagnosis was found in 43 (45.8%) patients. The most common pathogens identified in patients with severe CAP were Staphylococcus aureus (28.6%) and Klebsiella pneumoniae (28.6%), followed by Pseudomonas aeruginosa (17.9%). Patients with severe CAP had significantly more positive blood culture than patients with non-severe CAP (24% VS 4.5%; p = .008). Initial antibiotic treatment were discordant with the IDSA/ATS guidelines in 42% of all patients hospitalized with CAP, and 52% of patients with severe CAP. Multivariate analysis revealed that age (OR 1.1, 95% CI 1.01–1.1) and initial antibiotic treatment discordant to guidelines for severe CAP in ICU (OR 4.6, 95% CI 1.3–17.1) were independent risk factors of the unfavorable outcome of patients with severe CAP. Patients with unfavorable outcome had lower number of hospital-free days than patients with favorable outcome (5.2 ± 8 days VS 18 ± 7.1 days; p < .001).ConclusionsPatients with severe CAP outside ICU should be recognized for appropriate initial antibiotic selection to improve outcomes.

A case of herbicide-induced acute fibrinous and organizing pneumonia?

BackgroundTo improve the understanding of acute fibrinous and organizing pneumonia (AFOP), we present one case of AFOP proven by percutaneous lung biopsy along with clinical features, chest imaging and pathology.Case presentationA 50-year-old man was admitted to our department after he was given empiric therapy for community-acquired pneumonia (CAP). The clinical symptoms of the patient were dry cough, chills, night sweats and high fevers. Chest computed tomography (CT) scan showed a high-density shadow in the right lung lobe, similar to lobular pneumonia. The patient was preliminarily diagnosed with community-acquired pneumonia; however, antibacterial treatment was ineffective. To confirm the diagnosis, we performed bronchoscopy and percutaneous lung biopsy; pathology was consistent with AFOP. After he was treated with glucocorticoids, the patient’s symptoms were relieved, and the shadow seen on imaging dissipated during the follow-up period.ConclusionsAFOP is a rare histopathological diagnosis that can be easily misdiagnosed. Clinicians need to consider the possibility of AFOP in the case of invalid antibacterial therapy.

Enterovirus-Human Rhinovirus: A Rare Cause of Acute Respiratory Distress Syndrome.

A 22-year-old Asian woman presented with respiratory distress, cough, and wheezing for 1 week. Prior history included asthma and Turner syndrome. On presentation to the emergency department, the patient was hypotensive, tachycardic, tachypneic, with an oxyhemoglobin saturation in the mid 80% range while breathing ambient air. Chest radiograph revealed pulmonary vascular congestion and a left lower lobe infiltrate. Endotracheal intubation, mechanical ventilation, and vasopressors were initiated. Empiric therapy for community-acquired pneumonia was administered utilizing broad-spectrum intravenous antibiotics. Routine sputum culture was negative for pathogens. Nasopharyngeal swab submitted for multiplex amplified nucleic acid testing yielded enterovirus-human rhinovirus (EV-HRV). Thus, the diagnosis of EV-HRV pneumonia complicated by acute respiratory distress syndrome (ARDS) was established. Multiple attempts to wean from the ventilator were unsuccessful, and a tracheostomy was performed. This report highlights EV-HRV as a cause of severe ARDS and prolonged respiratory failure in adults.

Are third-generation cephalosporins unavoidable for empirical therapy of community-acquired pneumonia in adult patients who require ICU admission? A retrospective study

BackgroundThird-generation cephalosporins (3GCs) are recommended for empirical antibiotic therapy of community-acquired pneumonia (CAP) in patients requiring ICU admission. However, their extensive use could promote the emergence of extended-spectrum beta-lactamases-producing Enterobacteriaceae. Our aim was to assess whether the use of 3GCs in patients with CAP requiring ICU admission was justified.Methods We assessed all patients with CAP who required ICU admission during a 7-year period. We recorded empirical and definitive antibiotic therapies and susceptibility of causative pathogens. Amoxicillin, amoxicillin/clavulanate (A/C) susceptibilities as well as amikacin susceptibility of A/C-resistant strains were recorded.Results From January 2007 to March 2014, 391 patients were included in the study. Empirical 3GCs were used in 215 patients (55%). Among 267 patients with microbiologically documented CAP (68%), 241 received a beta-lactam as definitive therapy, and of those, 3CGs were chosen for 43 patients (18%). Amoxicillin or A/C was active against isolated pathogens in 159 patients (66%), while 39 patients (16%) required a beta-lactam with a broader spectrum than 3GCs. Ninety-four per cent of A/C-resistant strains were amikacin susceptible.Conclusions In ICU patients with CAP, 3GCs given on an empirical basis are changed, according to microbiological documentation, for another beta-lactam in 82% of cases especially to A/C in the absence of resistance risk factor. In patients evidencing risk factors for A/C-resistant strains infection, 3GCs or antipseudomonal beta-lactams including carbapenem associated with amikacin in the most severe patients seem a relevant empirical antibiotic therapy. This strategy could decrease 3GCs’ use.

Community-acquired pneumonia in adult HIV-infected patients: course, treatment, and prevention

This is a review of published data on community-acquired pneumonia (CAP) in adult HIV-infected patients. Morbidity of bacterial pneumonia in HIV-infected patients is 5- to 10-fold higher than that in general population. Wide use of antiretroviral therapy (ARVT) is associated with a reduction in morbidity of CAP in HIV-infected patients, but this reduction is not as significant as for other opportunistic infections. The most important risk factors for CAP are drug abuse, tobacco smoking, HIV-associated immunosuppression, hepatic cirrhosis, not to be treated with ARVT or ARVT withdrawal. Severe, complicated and invasive course of CAP and poor outcomes are seen more often in HIV-infected patients compared to general population. Bacterial pneumonia should be differed from pneumonia caused by Pneumocystis and from tuberculosis, especially in endemic countries and in patients with insidious onset of the disease. The standard therapy of CAP is applied in all patients independently of HIV status. However, administration of fluoroquinolones is restricted in regions with high prevalence of multi-drug resistant tuberculosis in HIV-infected patients before tuberculosis is excluded. Several studies have demonstrated that, in case of false initial diagnosis, 10-day monotherapy with a fluoroquinolone could form the resistance of Mycobacteria tuberculosis against this drug; this significantly complicates further treatment of tuberculosis and increases the treatment cost. Beta-lactams are not effective against tuberculosis; in 2016, WHO excluded macrolides from the list of medications for therapy of tuberculosis due to their low activity against M. tuberculosis. Therefore, empirical therapy of CAP in HIV-infected patients should be started with combination of beta-lactam antibiotic and newer macrolide. A strong protective effect of PPV23 vaccine against CAP was confirmed in HIV-infected patients, but the highest protective efficacy was seen in patients with relatively preserved immunity compared to patients with CD4 < 200 cells × µL -1 .

Scrub typhus in Uttarakhand & adjoining Uttar Pradesh: Seasonality, clinical presentations & predictors of mortality.

Background & objectives:Scrub typhus is a re-emerging mite-borne rickettsiosis, which continues to be underdiagnosed, with lethal consequences. The present study was conducted to determine the seasonality, clinical presentation and predictors of mortality in patients with scrub typhus at a tertiary care teaching hospital in northern India.Methods:Scrub typhus was suspected in patients attending the hospital as per the standard case definition and serological evidence was obtained by performing an IgM ELISA.Results:A total of 284 patients with scrub typhus from urban and rural areas were seen, predominantly from July to November. The most common clinical presentation was a bilateral community-acquired pneumonia (CAP), which resembled pneumonia due to atypical pathogens and often progressed to acute respiratory distress syndrome (ARDS). An acute undifferentiated febrile illness (AUFI) or a febrile illness associated with altered sensorium, aseptic meningitis, shock, abdominal pain, gastrointestinal bleeding or jaundice was also seen. Eschars were seen in 17 per cent of patients, and thrombocytopenia, transaminitis and azotaemia were frequent. There were 24 deaths (8.5%) caused predominantly by ARDS and multi-organ dysfunction. The mortality in patients with ARDS was high (37%). ARDS [odds ratio (OR)=38.29, 95% confidence interval (CI): 9.93, 147.71] and acute kidney injury (OR=8.30, 95% CI: 2.21, 31.21) were the major predictors of death.Interpretation & conclusions:The present findings indicate that scrub typhus may be considered a cause of CAP, ARDS, AUFI or a febrile illness with multisystem involvement, in Uttarakhand and Uttar Pradesh, especially from July to November. Empiric therapy of CAP may include doxycycline or azithromycin to ensure coverage of underlying unsuspected scrub typhus.

Empirical Therapy of Community-Acquired Pneumonia: Advancing Evidence or Just More Doubt?

Pneumonia remains a significant cause ofmorbidity andmortality, whether community acquired (CAP) or hospital acquired. Althoughmanymicrobial pathogensmaycausepneumonia, themost commonlyencounteredarepneumococcus;atypicalorganisms,such as Mycoplasma pneumoniae or Legionella; and at times Staphylococcus aureus and certain gram-negative rods. As diagnostic tests have increased in availability and sophistication, identifying multiple pathogens in the same patient is increasingly common. Cliniciansrarelyknowtheetiologicpathogensatthetimeofchoosing antibiotic therapy. In the outpatient setting, not knowing the correct pathogen is usually not too important because most antimicrobialsprovidesufficientantibacterial coveragefor the likelypathogens andoverallmortality ratesaregenerally less than 1%.Forhospitalized patients,thestakesarehigherbecausethemortalityriskishigh(reports vary from 4%-23%),1 and a more diverse group of pathogens is encountered than in the outpatient setting. A number of evidencebased national guidelines have been prepared to assist physicians in selecting initial antibiotics, and adherence to a guideline appropriate for the local environment improves patient outcomes.2,3 Even though treatment options for pneumonia have improved, the best empirical therapy for CAP remains unclear. Two questions in particular have caused much debate in the past deJAMA INTERNALMEDICINE

Distribution and antimicrobial susceptibility of bacteria from adults with community-acquired pneumonia or complicated skin and soft tissue infections in France: the nationwide French PREMIUM study

The empirical therapy of community-acquired pneumonia (CAP) and complicated skin and soft tissue infections (cSSTIs) must be based on updated bacterial distribution and susceptibility data. A nationwide study consecutively collected 1288 isolates from CAP (n=467) and cSSTIs (n=821) from 18 French hospitals between 2012 and 2013. The MIC values of commonly used antimicrobial agents, including ceftaroline, were determined. Bacterial distribution featured Pneumococcus, Haemophilus influenzae, and Staphylococcus aureus for CAPs and S. aureus, β-hemolytic streptococci and Enterobacteriaceae for cSSTIs. Antimicrobial susceptibility testing indicated i) the sustained third-generation cephalosporins and levofloxacin activity against pneumococci and H. influenzae, ii) no methicillin-resistant Staphylococcus aureus emergence among respiratory pathogens, iii) the high in vitro activity of ceftaroline against staphylococci from cSSTIs (98.7% susceptibility), and iv) the worrisome decreasing fluoroquinolone and third-generation cephalosporin susceptibilities among Enterobacteriaceae. This laboratory-based survey depicts a contrasting situation and supports the scoring of patients for the resistant pathogen risk before empirical therapy.

Searching for the Optimal Treatment of Ceftriaxone-Resistant Streptococcus pneumoniae in Community-Acquired Pneumonia

Ceftriaxone-resistant Streptococcus pneumoniae (CRSP) (minimal inhibitory concentration > 1 mcg/mL) is a growing major concern in the optimal selection of empirical antimicrobial treatment of community-acquired pneumonia (CAP). It has been estimated that up to 37.9% of S. pneumoniae are resistant to ceftriaxone in the United States in 2012,1 with a mean of 19.2% in Europe including greater than 25% in Eastern Europe (Bulgaria, Romania, and Turkey) in 20112 and 18.5% in China in 2011.3 This high rate of CRSP has been in part correlated with the introduction of the PCV7 in 2001 and of PCV13 in 2010 and the selection of serotypes 19A, 6C, and 22F.4,5 The increasing use of antimicrobials in humans and in food-producing animals among others is expected to contribute to the rising rate of CRSP.6 Mutation of cell wall penicillin-binding protein (PBP), particularly PBP1a, PBP2x, and PBP2b, was associated with CRSP.7 Because S. pneumoniae is the most common etiologic agent of CAP, physicians should optimize the empirical therapy of CAP in areas with a high rate of CRSP. Wenzler et al8 examined in this issue the clinical outcomes of patients with CRSP (minimal inhibitory concentration > 1 mcg/mL) versus ceftriaxone-susceptible S. pneumoniae in adult patients with pneumonia and respiratory culture positive for S. pneumoniae. Regardless of the sample size limitation, this study has striking findings. None of the patients with CRSP infection had 90 days of previous exposure of ceftriaxone. Time to clinical cure was longer in patients with CRSP (4 [1–5] vs 8 [3–12] days, P = 0.51), and length of stay was longer for patients with CRSP (17 [9–23] vs 9 [7–13] days, P = 0.46). The empirical treatment was changed in 50% of the patients with CRSP infection versus 0% in those with ceftriaxone-susceptible pneumoniae infection. A 50% of patients with CRSP infection were treated with fluoroquinolones, and 70% were treated with either vancomycin or linezolid. Among other findings, 70% of the patients with CRSP infection had pneumonia severity index of IV or greater. Overall, both groups had similar clinical outcomes although these outcomes may not have been similar if patients with CRSP infection were treated with ceftriaxone according to CAP treatment guidelines. Large prospective studies are needed to validate the optimal treatment of CRSP CAP. Current options for the treatment of CRSP CAP are fluoroquinolones, vancomycin, linezolid, and ceftaroline. Ceftaroline is the first of the growing group of active cephalosporins against methicillin-resistant Staphylococcus aureus and it also has activity against CRSP. Ceftaroline showed sustained bactericidal activity against CRSP in a pharmacokinetics and pharmakodynamics model study.9 This ceftaroline activity was validated in a rabbit model at a simulated human dose of 20 mg/kg by reducing 6 log units of CRSP in the lungs.10 Furthermore, a second analysis of studies focus 1 and 2 revealed that patients with S. pneumoniae CAP treated with ceftaroline had more favorable outcome than patients treated with ceftriaxone (odds ratio, 2.6; 95% confidence interval, 1.11–6.17; P = 0.0286).11 An approach in the empirical therapy of CRSP CAP could be a similar strategy used for bacterial meningitis by adding vancomycin to ceftriaxone treatment. Current Infectious Diseases Society of America guidelines do not recommend the use of vancomycin in cases with severe CAP nor CRSP. Vancomycin has a limited bactericidal activity when compared with β-lactams. Although levofloxacin and moxifloxacin have effective activity against CRSP, fluoroquinolones use has been reported to trigger higher rates of multiple drug resistance Pseudomonas, methicillin-resistant Staphylococcus aureus, and Clostridium difficile infections.12 In contrast to linezolid, ceftaroline has a spectrum similar to ceftriaxone covering gram-negative rods, including those etiologic organisms of CAP such as Klebsiella spp., Haemophilus spp., and Moraxella. In summary, physicians should consider antimicrobials with activity against CRSP in patients with CAP residing in areas with substantial prevalence of CRSP, in particular, those from the US southern states, having history of previous antibiotic therapy, and being immunocompromised.1,6 This concern is critical in patients with advanced comorbidities and increased risk for poor outcomes. Current data support more the use of ceftaroline treatment in cases with suspected CRSP pneumonia. Physicians should be cautious to use fluoroquinolones treatment of CRSP infection given the risk for antimicrobial resistance. Other treatment options include vancomycin although it has limited bactericidal activity compared with β-lactams and linezolid, which has the advantage of 100% of intestinal absorption that makes it a candidate for oral therapy.

Effectiveness of Antimicrobial Guidelines for Community-Acquired Pneumonia in Children

To assess the effectiveness of guidelines and education on empirical therapy for community-acquired pneumonia. Administrative records for children with a primary diagnosis of pneumonia from January 2007 to September 2009 were reviewed. Antimicrobial use was measured monthly over 3 periods: (1) before creation of an antimicrobial stewardship task force (ASTF), (2) after ASTF formation but before release of guidelines for antimicrobial use, and (3) after guideline release. Antimicrobial use over time was assessed by using quasi-binomial logistic regression models that incorporated interrupted events, seasonality, and autocorrelation. Allowing calculation of immediate changes due to specific interventions and trends in use over each time period. The primary outcome was use of ampicillin as recommended in the guidelines versus ceftriaxone, the historical standard. Secondary outcomes included other antimicrobial use, length of stay, mortality, and readmission. One thousand two hundred forty-six children met study criteria. Ampicillin use increased from 2% at baseline to 6% after ASTF formation and 44% after guideline release. Ceftriaxone use increased slightly (from 56% to 59%) after ASTF formation but decreased to 28% after guideline release. An immediate change in prescription occurred in the month after guideline publication and remained stable over the following year. Guidelines and education can have an impact on antimicrobial use in the pediatric setting. Although the optimal strategies for pediatric antimicrobial stewardship programs still are being determined, we believe that our approach offers an inexpensive and low-risk step in the right direction.

Does empirical treatment of community-acquired pneumonia with fluoroquinolones delay tuberculosis treatment and result in fluoroquinolone resistance in Mycobacterium tuberculosis? Controversies and solutions

The role of fluoroquinolones (FQs) as empirical therapy for community-acquired pneumonia (CAP) remains controversial in countries with high tuberculosis (TB) endemicity owing to the possibility of delayed TB diagnosis and treatment and the emergence of FQ resistance in Mycobacterium tuberculosis. Although the rates of macrolide-resistant Streptococcus pneumoniae and amoxicillin/clavulanic acid-resistant Haemophilus influenzae have risen to alarming levels, the rates of respiratory FQ (RFQ) resistance amongst these isolates remain relatively low. It is reported that ca. 1–7% of CAP cases are re-diagnosed as pulmonary TB in Asian countries. A longer duration (≥7 days) of symptoms, a history of night sweats, lack of fever (>38°C), infection involving the upper lobe, presence of cavitary infiltrates, opacity in the lower lung without the presence of air, low total white blood cell count and the presence of lymphopenia are predictive of pulmonary TB. Amongst patients with CAP who reside in TB-endemic countries who are suspected of having TB, imaging studies as well as aggressive microbiological investigations need to be performed early on. Previous exposure to a FQ for >10 days in patients with TB is associated with the emergence of FQ-resistant M. tuberculosis isolates. However, rates of M. tuberculosis isolates with FQ resistance are significantly higher amongst multidrug-resistant M. tuberculosis isolates than amongst susceptible isolates. Consequently, in Taiwan and also in other countries with TB endemicity, a short-course (5-day) regimen of a RFQ is still recommended for empirical therapy for CAP patients if the patient is at low risk for TB.

Adherence to infectious diseases society of America guidelines for empiric therapy for patients with community-acquired pneumonia in a commercially insured cohort

Background: There is little published research addressing how the 2003 Infectious Diseases Society of America (IDSA) guidelines for empiric therapy of community-acquired pneumonia (CAP) are implemented in clinical practice. Objective: This study was designed to describe antibiotic treatment patterns among patients with CAP treated in ambulatory settings in light of the IDSA guidelines. Methods: Health insurance claims data from a large managed care organization with −30 million enrollees located in geographically diverse regions of the United States were analyzed. Patients ≥18 years of age with CAP who received a prescription for any antibiotic in an ambulatory setting during 2004 were identified via International Classification of Diseases, Ninth Revision, Clinical Modification codes for diagnosis (481–486). Recent antibiotic use was defined as receipt of any antibiotics <90 days before the date of diagnosis. Antibiotics were identified through National Drug Codes and from outpatient medical claims data with the use of J codes. Individuals were classified, per IDSA guidelines, as previously healthy without recent antibiotic use (group 1); previously healthy with recent antibiotic use (group 2); with comorbidities and without recent antibiotic use (group 3); and with comorbidities and recent antibiotic use (group 4). The guideline adherence was calculated using the number of patients receiving recommended treatment divided by the total number of patients in each group. Results: Of 34,342 patients identified, 76.5% had no reported comorbidities. Among group-1 patients, 52.0% received the recommended empiric therapy (macrolide or doxycycline). In group-2 patients, 42.5% received the recommended therapy (respiratory quinolone alone or advanced-generation macrolide plus amoxicillin or amoxicillin-clavulanate). A high rate of compliance with recommended empiric therapy (advanced-generation macrolides or respiratory quinolones) was observed in group-3 patients (81.5%). In group-4 patients, 43.4% received the recommended therapy (respiratory quinolone or advanced-generation macrolide plus ß-lactam). Patients whose therapy was adherent with the guidelines had fewer respiratory-infection-related hospital admissions within 30 days after initiation of antibiotic treatment (overall, relative risk = 0.81 [95% CI, 0.71–0.94]). Conclusion: Although these data reflect a period shortly after the 2003 IDSA guidelines were published, they suggest that there is room for improvement with regard to choice of empiric antibiotic therapy among these patients with CAP treated in ambulatory settings.

Community-acquired pneumonia in Shanghai, China: microbial etiology and implications for empirical therapy in a prospective study of 389 patients

The aim of this multicenter study was to identify the causative pathogens of community-acquired pneumonia (CAP) in Shanghai, China, and to determine their susceptibility to antimicrobial agents. Pathogens obtained from 389 patients with documented CAP during 2001-2003 were identified by multiple diagnostic tools that included bacterial culture, polymerase chain reaction (PCR), and specific immunological assays. Susceptibility of the bacterial isolates was tested by the broth microdilution method. A specific pathogen was identified in 39.8% (155/389) of the patients: Haemophilus influenzae (n=80), Klebsiella spp. (n=15), Streptococcus pneumoniae (n=12), Staphylococcus aureus (n=6), Moraxella catarrhalis (n=1), other gram-negative organisms (n=9), and atypical pathogens that comprised Mycoplasma pneumoniae (n=42), Chlamydia pneumoniae (n=17), and Legionella pneumophila (n=2). Most H. influenzae isolates were susceptible to ampicillin (88.3%), and all were susceptible to macrolides. Of the S. pneumoniae isolates, 75% (9/12) were susceptible to penicillin, while 25% (3/12) were intermediately susceptible. H. influenzae and atypical pathogens are among the most important pathogens of CAP. Ampicillin, cephalosporins, and the newer fluoroquinolones can be used as empirical therapy for CAP in the Shanghai area. The efficacy of monotherapy with newer macrolides for CAP caused by S. pneumoniae requires further evaluation.