To review the evidence for trimethoprim-sulfamethoxazole (TMP-SMX), clindamycin, doxycycline, and minocycline in the treatment of methicillin-resistant (MRSA) pneumonia. MEDLINE, PubMed, EMBASE, Google, Google Scholar, Cochrane Central Register of Controlled Trials from 1946 to May 20, 2019. The search was performed with the keywords methicillin-resistant , MRSA, , pneumonia, trimethoprim, sulfamethoxazole drug combination, trimethoprim, sulfamethoxazole, TMP-SMX, co-trimoxazole, clindamycin, doxycycline, and minocycline. Studies reporting the use of the above antibiotics for MRSA pneumonia treatment with clinical outcomes were included. Search parameters were limited to English language and human studies only. The search yielded 16 relevant articles: 6 TMP-SMX, 8 clindamycin, zero doxycycline, and 2 minocycline. For TMP-SMX, prospective randomized trials showed variable results; however, these studies were not specifically designed to assess MRSA pneumonia treatment. Retrospective studies with clindamycin suggested that it could be used as monotherapy or in combination with other anti-MRSA antibiotics. There was no evidence for doxycycline use, but 2 small retrospective reviews appeared to support minocycline as a treatment option. These antibiotics are often used in clinical practice as potential treatment options for MRSA pneumonia. This article reviews the evidence for the clinical efficacy and safety of these agents. There are limited data to support use of TMP-SMX, clindamycin, doxycycline, or minocycline in MRSA pneumonia treatment. Randomized controlled trials are required to determine the effectiveness of these antibiotics. Clinicians should base their decision to use these agents on a case-by-case basis depending on clinical status and susceptibility results.

Background: is a multidrug-resistant organism with limited antibiotic treatment options. Minocycline and doxycycline may be appropriate, but clinical data are limited.

Objective: To compare tetracyclines (minocycline and doxycycline [TCN]) with standard of care, sulfamethoxazole-trimethoprim (TMP-SMZ), in pneumonia treatment.

Methods: This retrospective, 2-center study evaluated patients treated for pneumonia with TCN or TMP-SMZ for clinical success, defined as resolution of leukocytosis, fever, and tachypnea. Patients were classified as treatment with TCN or TMP-SMZ based on definitive agent used for ≥50% of the treatment course and ≥4 days. Inclusion criteria were age ≥18 years, confirmed on respiratory culture from January 2013 to November 2020, and appropriate definitive antibiotic dosing. Pregnancy, incarceration, -resistant or intermediate to definitive therapy, and combination therapy for treatment of pneumonia were exclusion criteria. Secondary outcomes were microbiologic success and recurrence or reinfection within 30 days requiring treatment.

Results: A total of 80 patients were included (21 TCN [15 minocycline, 6 doxycycline], 59 TMP-SMZ). There was no difference in clinical success (28.6% vs 25.4%; = 0.994), microbiologic success (n = 28, 55.6% vs 66.4%; = 0.677), or recurrence or reinfection (n = 24, 66.7% vs 26.7%; = 0.092) between TCN and TMP-SMZ, respectively.

Conclusion And Relevance: Clinical and microbiologic success rates were similar in patients treated with TCN compared with TMP-SMZ for pneumonia. These data suggest minocycline and doxycycline may be options to treat pneumonia, but conclusive clinical data continue to be lacking.

difficile_ infection or risk factors related to U.S. Food and Drug Administration warnings (). The panel recommends using doxycycline as an alternative to a macrolide in combination with a β-lactam as a third option in the presence of documented allergies or contraindications to macrolides or fluoroquinolones or clinical failure on one of those agents. Of note, a newer member of the tetracycline class, omadacycline, was recently reported to be equivalent to moxifloxacin as monotherapy for adults with nonsevere CAP and is effective in the setting of tetracycline resistance (). However, as this is a single published report and the safety information is less well established, the committee decided to not list this new agent as an alternative to the currently recommended treatment options.
The panel also considered β-lactam monotherapy as an option for inpatients with nonsevere CAP. An RCT in 580 patients with CAP could not rule out the possibility that β-lactam monotherapy was inferior to β-lactam/macrolide therapy for inpatients with CAP (). Nie and colleagues identified several cohort (_n_ = 4) and retrospective observational (_n_ = 12) studies addressing this question and found that β-lactam/macrolide therapy reduced mortality in patients with CAP compared with patients treated with β-lactam monotherapy (). Similarly, Horita and colleagues demonstrated that β-lactam/macrolide combinations may decrease all-cause death, but mainly for patients with severe CAP (). Therefore, we suggest that β-lactam monotherapy should not be routinely used for inpatients with CAP over fluoroquinolone monotherapy or β-lactam/macrolide combination therapy.

There are limited data to inform the choice between different agents active against MRSA. Vancomycin and linezolid have been best studied. Meta-analyses of RCTs comparing vancomycin and linezolid suggest that they are associated with similar clinical outcomes [] (see section XV). Other theoretical choices include teicoplanin, telavancin, ceftaroline, and tedizolid []. Two randomized clinical trials evaluated teicoplanin vs vancomycin or linezolid for gram-positive infections [, ]. However, multiple sites of infection were included in both studies and small numbers of patients with pneumonia were evaluated, and a small number of patients with documented MRSA pneumonia were evaluated. Thus, more evidence is needed to define the clinical role of teicoplanin in patients with HAP/VAP. Two RCTs comparing telavancin and vancomycin found similar outcomes for both agents, but <10% of patients in these trials had MRSA VAP, and patients with moderate to severe renal dysfunction (creatinine clearance <50 mL/min) randomized to telavancin had higher mortality rates [, , ]. There are no published RCTs evaluating ceftaroline or tedizolid for the treatment of MRSA VAP. Daptomycin is inactivated by surfactant and is therefore not used for treatment of pneumonia. RCTs comparing tigecycline to imipenem and ceftobiprole to ceftazidime noted significantly lower clinical cure rates among VAP patients randomized to tigecycline and ceftobiprole, respectively [, ].

To review the evidence for trimethoprim-sulfamethoxazole (TMP-SMX), clindamycin, doxycycline, and minocycline in the treatment of methicillin-resistant (MRSA) pneumonia. MEDLINE, PubMed, EMBASE, Google, Google Scholar, Cochrane Central Register of Controlled Trials from 1946 to May 20, 2019. The search was performed with the keywords methicillin-resistant , MRSA, , pneumonia, trimethoprim, sulfamethoxazole drug combination, trimethoprim, sulfamethoxazole, TMP-SMX, co-trimoxazole, clindamycin, doxycycline, and minocycline. Studies reporting the use of the above antibiotics for MRSA pneumonia treatment with clinical outcomes were included. Search parameters were limited to English language and human studies only. The search yielded 16 relevant articles: 6 TMP-SMX, 8 clindamycin, zero doxycycline, and 2 minocycline. For TMP-SMX, prospective randomized trials showed variable results; however, these studies were not specifically designed to assess MRSA pneumonia treatment. Retrospective studies with clindamycin suggested that it could be used as monotherapy or in combination with other anti-MRSA antibiotics. There was no evidence for doxycycline use, but 2 small retrospective reviews appeared to support minocycline as a treatment option. These antibiotics are often used in clinical practice as potential treatment options for MRSA pneumonia. This article reviews the evidence for the clinical efficacy and safety of these agents. There are limited data to support use of TMP-SMX, clindamycin, doxycycline, or minocycline in MRSA pneumonia treatment. Randomized controlled trials are required to determine the effectiveness of these antibiotics. Clinicians should base their decision to use these agents on a case-by-case basis depending on clinical status and susceptibility results.

Background: is a multidrug-resistant organism with limited antibiotic treatment options. Minocycline and doxycycline may be appropriate, but clinical data are limited.

Objective: To compare tetracyclines (minocycline and doxycycline [TCN]) with standard of care, sulfamethoxazole-trimethoprim (TMP-SMZ), in pneumonia treatment.

Methods: This retrospective, 2-center study evaluated patients treated for pneumonia with TCN or TMP-SMZ for clinical success, defined as resolution of leukocytosis, fever, and tachypnea. Patients were classified as treatment with TCN or TMP-SMZ based on definitive agent used for ≥50% of the treatment course and ≥4 days. Inclusion criteria were age ≥18 years, confirmed on respiratory culture from January 2013 to November 2020, and appropriate definitive antibiotic dosing. Pregnancy, incarceration, -resistant or intermediate to definitive therapy, and combination therapy for treatment of pneumonia were exclusion criteria. Secondary outcomes were microbiologic success and recurrence or reinfection within 30 days requiring treatment.

Results: A total of 80 patients were included (21 TCN [15 minocycline, 6 doxycycline], 59 TMP-SMZ). There was no difference in clinical success (28.6% vs 25.4%; = 0.994), microbiologic success (n = 28, 55.6% vs 66.4%; = 0.677), or recurrence or reinfection (n = 24, 66.7% vs 26.7%; = 0.092) between TCN and TMP-SMZ, respectively.

Conclusion And Relevance: Clinical and microbiologic success rates were similar in patients treated with TCN compared with TMP-SMZ for pneumonia. These data suggest minocycline and doxycycline may be options to treat pneumonia, but conclusive clinical data continue to be lacking.

Few data exist on the clinical utility of the expanded-spectrum tetracyclines doxycycline and minocycline for the treatment of community-associated methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTI). We performed a retrospective cohort study of 276 patients who presented with 282 episodes of MRSA SSTI to the emergency room or outpatient clinic at two tertiary medical centers between October 2002 and February 2007. The median percentage of patients infected with MRSA strains that were susceptible to tetracycline was 95%. Time zero was defined as the time of the first incision and drainage procedure or, if none was performed, the time of the first positive wound culture. The median patient age was 48 years. Abscesses constituted the majority of clinical presentations (75%), followed by furuncles or carbuncles (13%) and cellulitis originating from a purulent focus of infection (12%). A total of 225 patients (80%) underwent incision and drainage. Doxycycline or minocycline was administered in 90 episodes (32%); the other 192 SSTI were treated with beta-lactams. Treatment failure, defined as the need for a second incision and drainage procedure and/or admission to the hospital within at least 2 days after time zero, was diagnosed in 28 episodes (10%) at a median of 3 days after time zero. On logistic regression analysis, receipt of a beta-lactam agent was the only clinical characteristic associated with treatment failure (adjusted odds ratio, 3.94; 95% confidence interval, 1.28 to 12.15; P = 0.02). The expanded-spectrum tetracyclines appear to be a reasonable oral treatment option for patients with community onset MRSA SSTI in areas where MRSA strains are susceptible to the tetracyclines.

Background: Few data exist on the efficacy of the long-acting tetracyclines doxycycline and minocycline against methicillin-resistant Staphylococcus aureus (MRSA) infection.

Methods: The medical records of 24 patients with serious tetracycline-susceptible MRSA infections who were treated with doxycycline or minocycline were reviewed. A review of the literature on the use of these antibiotics for treatment of both methicillin-susceptible and methicillin-resistant S. aureus infection was also performed.

Results: Complicated skin and skin-structure infections were most common (67%). Clinical cure was achieved in 20 (83%) of 24 patients in our case series. Both drugs were well-tolerated. The review of the literature on a total of 85 patients with S. aureus infection revealed similar results.

Conclusions: Long-acting tetracyclines may be a reasonable treatment alternative for patients with certain types of MRSA infection.

To review the evidence for trimethoprim-sulfamethoxazole (TMP-SMX), clindamycin, doxycycline, and minocycline in the treatment of methicillin-resistant (MRSA) pneumonia. MEDLINE, PubMed, EMBASE, Google, Google Scholar, Cochrane Central Register of Controlled Trials from 1946 to May 20, 2019. The search was performed with the keywords methicillin-resistant , MRSA, , pneumonia, trimethoprim, sulfamethoxazole drug combination, trimethoprim, sulfamethoxazole, TMP-SMX, co-trimoxazole, clindamycin, doxycycline, and minocycline. Studies reporting the use of the above antibiotics for MRSA pneumonia treatment with clinical outcomes were included. Search parameters were limited to English language and human studies only. The search yielded 16 relevant articles: 6 TMP-SMX, 8 clindamycin, zero doxycycline, and 2 minocycline. For TMP-SMX, prospective randomized trials showed variable results; however, these studies were not specifically designed to assess MRSA pneumonia treatment. Retrospective studies with clindamycin suggested that it could be used as monotherapy or in combination with other anti-MRSA antibiotics. There was no evidence for doxycycline use, but 2 small retrospective reviews appeared to support minocycline as a treatment option. These antibiotics are often used in clinical practice as potential treatment options for MRSA pneumonia. This article reviews the evidence for the clinical efficacy and safety of these agents. There are limited data to support use of TMP-SMX, clindamycin, doxycycline, or minocycline in MRSA pneumonia treatment. Randomized controlled trials are required to determine the effectiveness of these antibiotics. Clinicians should base their decision to use these agents on a case-by-case basis depending on clinical status and susceptibility results.

Delafloxacin is a novel fluoroquinolone with activity against Gram-positive, Gram-negative, and atypical pathogens, including fluoroquinolone-nonsusceptible methicillin-resistant (MRSA). The microbiological results of a phase 3 clinical trial in adults with community-acquired pneumonia (CAP) comparing delafloxacin (300 mg intravenously [i.v.] with the option to switch to 450 mg orally every 12 h) to moxifloxacin (400 mg i.v. with the option to switch to 400 mg orally once a day [QD]) were determined. Patients from 4 continents, predominately Europe but also South America and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 520 patients, and 60.5% of these patients had a bacterial pathogen identified. Multiple diagnostic methods were employed, including culture, serology, PCR, and urinary antigen tests. Based on baseline MIC values, delafloxacin exhibited at least 16-fold greater activity than moxifloxacin for Gram-positive and fastidious Gram-negative pathogens. Delafloxacin retained activity against resistant phenotypes found in (penicillin-, macrolide-, and multiple-drug resistant), species (β-lactamase producing and macrolide nonsusceptible), and (MRSA and fluoroquinolone-nonsusceptible methicillin-susceptible [MSSA]). The microbiological success rates were 92.7% for (87.5% for penicillin-resistant [PRSP]), 92.6% for (100% for MRSA), 100% for , 82.4% for , 100% for , 100% for , 91.7% for , 88.6% for , 96.7% for , 93.1% for , and 100% for There was little correlation between MICs and outcomes, with a high proportion of favorable outcomes observed across all delafloxacin baseline MIC values. Delafloxacin may be considered a treatment option as monotherapy for CAP in adults, where broad-spectrum coverage including MRSA activity is desirable.

Increasing antimicrobial resistance in community-acquired pneumonia (CAP) pathogens has contributed to infection-related morbidity and mortality. Delafloxacin is a novel fluoroquinolone with broad-spectrum activity against Gram-positive and -negative organisms, including Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to define the pharmacodynamic profile of delafloxacin against CAP pathogens using a neutropenic murine lung infection model. Five S. pneumoniae, 2 methicillin-susceptible S. aureus (MSSA), 2 MRSA and 2 Klebsiella pneumoniae isolates were studied. Delafloxacin doses varied from 0.5 mg/kg/day to 640 mg/kg/day and were given as once-daily to every 3 h regimens over the 24-h treatment period. Efficacy was measured as the change in log CFU at 24 h compared with 0-h controls. Plasma and bronchopulmonary pharmacokinetic studies were conducted. Delafloxacin demonstrated potent in vitro and in vivo activity. Delafloxacin demonstrated high penetration into the lung compartment, as epithelial lining fluid concentrations were substantially higher than free drug in plasma. The ratio of the area under the free drug concentration-time curve to the minimum inhibitory concentration of the infecting organism (fAUC/MIC) was the parameter that best correlated with the efficacy of the drug, and the magnitude required to achieve 1 log CFU reduction was 31.8, 24.7, 0.4 and 9.6 for S. pneumoniae, MRSA, MSSA and K. pneumoniae, respectively. The observed in vivo efficacy of delafloxacin was supported by the high pulmonary disposition of the compound. The results derived from this pre-clinical lung model support the continued investigation of delafloxacin for the treatment of community-acquired lower respiratory tract infections.

149/177 (84.2) 148/183 (80.9) 154/177 (87.0) 153/183 (83.6) Methicillin-resistant 125/144 (86.8) 121/141 (85.8) 122/144 (84.7) 116/141 (82.3) Streptococcus pyogenes 17/23 (73.9) 9/18 (50.0) 21/23 (91.3) 16/18 (88.9) Staphylococcus haemolyticus 11/15 (73.3) 7/8 (87.5) 13/15 (86.7) 7/8 (87.5) Streptococcus agalactiae 10/14 (71.4) 9/12 (75.0) 12/14 (85.7) 11/12 (91.7) Streptococcus anginosus Group 59/64 (92.2) 55/61 (90.2) 54/64 (84.4) 47/61 (77.0) Staphylococcus lugdunensis 8/11 (72.7) 6/9 (66.7) 10/11 (90.9) 8/9 (88.9) Enterococcus faecalis 11/11 (100.0) 12/16 (75.0) 9/11 (81.8) 14/16 (87.5) Escherichia coli 12/14 (85.7) 16/20 (80.0) 12/14 (85.7) 18/20 (90.0) Enterobacter cloacae 10/14 (71.4) 8/11 (72.7) 12/14 (85.7) 10/11 (90.9) Klebsiella pneumoniae 19/22 (86.4) 22/23 (95.7) 20/22 (90.9) 21/23 (91.3) Pseudomonas aeruginosa 9/11 (81.8) 11/12 (91.7) 11/11 (100.0) 12/12 (100.0) 14.2 Community-Acquired Bacterial Pneumonia A total of 859 adults with CABP were randomized in a multicenter, multinational, double-blind, double-dummy, noninferiority trial comparing Baxdela (delafloxacin meglumine) to moxifloxacin (Trial 3, NCT 02679573).

As recent data supporting antibiotic administration for <5 days are scant, on a risk–benefit basis we recommend treating for a minimum of 5 days, even if the patient has reached clinical stability before 5 days. As most patients will achieve clinical stability within the first 48 to 72 hours, a total duration of therapy of 5 days will be appropriate for most patients. In switching from parenteral to oral antibiotics, either the same agent or the same drug class should be used.
We acknowledge that most studies in support of 5 days of antibiotic therapy include patients without severe CAP, but we believe these results apply to patients with severe CAP and without infectious complications. We believe that the duration of therapy for CAP due to suspected or proven MRSA or _P. aeruginosa_ should be 7 days, in agreement with the recent hospital-acquired pneumonia and ventilator-associated pneumonia guidelines ().

Delafloxacin is a novel fluoroquinolone with activity against Gram-positive, Gram-negative, and atypical pathogens, including fluoroquinolone-nonsusceptible methicillin-resistant (MRSA). The microbiological results of a phase 3 clinical trial in adults with community-acquired pneumonia (CAP) comparing delafloxacin (300 mg intravenously [i.v.] with the option to switch to 450 mg orally every 12 h) to moxifloxacin (400 mg i.v. with the option to switch to 400 mg orally once a day [QD]) were determined. Patients from 4 continents, predominately Europe but also South America and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 520 patients, and 60.5% of these patients had a bacterial pathogen identified. Multiple diagnostic methods were employed, including culture, serology, PCR, and urinary antigen tests. Based on baseline MIC values, delafloxacin exhibited at least 16-fold greater activity than moxifloxacin for Gram-positive and fastidious Gram-negative pathogens. Delafloxacin retained activity against resistant phenotypes found in (penicillin-, macrolide-, and multiple-drug resistant), species (β-lactamase producing and macrolide nonsusceptible), and (MRSA and fluoroquinolone-nonsusceptible methicillin-susceptible [MSSA]). The microbiological success rates were 92.7% for (87.5% for penicillin-resistant [PRSP]), 92.6% for (100% for MRSA), 100% for , 82.4% for , 100% for , 100% for , 91.7% for , 88.6% for , 96.7% for , 93.1% for , and 100% for There was little correlation between MICs and outcomes, with a high proportion of favorable outcomes observed across all delafloxacin baseline MIC values. Delafloxacin may be considered a treatment option as monotherapy for CAP in adults, where broad-spectrum coverage including MRSA activity is desirable.

Increasing antimicrobial resistance in community-acquired pneumonia (CAP) pathogens has contributed to infection-related morbidity and mortality. Delafloxacin is a novel fluoroquinolone with broad-spectrum activity against Gram-positive and -negative organisms, including Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to define the pharmacodynamic profile of delafloxacin against CAP pathogens using a neutropenic murine lung infection model. Five S. pneumoniae, 2 methicillin-susceptible S. aureus (MSSA), 2 MRSA and 2 Klebsiella pneumoniae isolates were studied. Delafloxacin doses varied from 0.5 mg/kg/day to 640 mg/kg/day and were given as once-daily to every 3 h regimens over the 24-h treatment period. Efficacy was measured as the change in log CFU at 24 h compared with 0-h controls. Plasma and bronchopulmonary pharmacokinetic studies were conducted. Delafloxacin demonstrated potent in vitro and in vivo activity. Delafloxacin demonstrated high penetration into the lung compartment, as epithelial lining fluid concentrations were substantially higher than free drug in plasma. The ratio of the area under the free drug concentration-time curve to the minimum inhibitory concentration of the infecting organism (fAUC/MIC) was the parameter that best correlated with the efficacy of the drug, and the magnitude required to achieve 1 log CFU reduction was 31.8, 24.7, 0.4 and 9.6 for S. pneumoniae, MRSA, MSSA and K. pneumoniae, respectively. The observed in vivo efficacy of delafloxacin was supported by the high pulmonary disposition of the compound. The results derived from this pre-clinical lung model support the continued investigation of delafloxacin for the treatment of community-acquired lower respiratory tract infections.