Multidrug-resistant Streptococcus Pneumoniae Research Articles

Characterization of MultidrugResistant serogroup 19 Streptococcus pneumoniae isolated from healthy children below 5 years of age in Indonesia.

We investigated the resistance genes, pilus islets, biofilm formation ability and sequence types of multidrug-resistant Streptococcus pneumoniae (MDRSP) isolated from healthy children below 5 years of age in Indonesia. In all, 104 archived MDRSP isolates from previous carriage studies in Indonesia in 2016-2019 were screened for the presence of antibiotic resistance genes and the rrgC (pilus islet 1) and pitB (pilus islet 2) genes. Multilocus sequence typing and biofilm formation were determined by PCR sequencing and the ability of cells to adhere to the walls, respectively. Results have shown that the mefA, ermB and tetM genes were found in 93, 52 and 100 % of MDRSP isolates, respectively. Insertions of arginine, proline and Ile-100-Leu were the most common mutations in the folA and folP genes. Pilus islets 1 and 2 were discovered in 93 and 82 % of MDRSP isolates, respectively. The MDRSP isolates showed no biofilm formation ability (64 %), and 5 out of 10 strains of MDRSP strains were ST1464. This finding can be used to provide further considerations in implementing and monitoring pneumococcal vaccination in Indonesia.

1463. Activity of Delafloxacin against Multi-Drug-Resistant Fastidious Respiratory Pathogens from European Medical Centers (2014-2019)

BackgroundDelafloxacin (DLX) is an anionic fluoroquinolone (FQ) that has been approved in the United States and in Europe for the treatment of acute bacterial skin and skin structure infections and was recently approved in the US for treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from European hospitals participating in the SENTRY Program during 2014-2019.MethodsA total of 2,835 SPN, 1,484 HI, 959 MC, and 20 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014-2019 from European hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and EUCAST (2020) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin (ERY), and tetracycline; other SPN phenotypes were ERY-NS, or penicillin (PEN)-NS. β-lactamase (BL) presence was determined for HI, HP, and MC.ResultsThe activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were the same when tested against the MDR or PEN-NS for SPN phenotypes. ERY-NS isolates had DLX MIC50/90 results of 0.015/0.03 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 1 HP isolate was BL-positive.ConclusionDLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. These data support the utility of DLX in CABP including when caused by antibiotic resistant strains.Table 1 DisclosuresJennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Robert K. Flamm, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)

Auranofin Has Advantages over First-Line Drugs in the Treatment of Severe Streptococcus suis Infections.

Streptococcal toxic shock-like syndrome (STSLS) likely occurs when an individual is infected with the Streptococcus suis (S. suis) epidemic strain and is characterized by a cytokine storm, multiple organ dysfunction syndrome (MODS) and a high incidence of mortality despite adequate treatment. A number of antibiotics exhibit excellent bactericidal effects in vivo, such as fluoroquinolones, aminoglycosides (gentamicin) and β-lactams (penicillin G, ceftiofur, or amoxicillin), but are less effective for treating STSLS. Therefore, there is an urgent need to identify new compounds that can reduce the damage caused by STSLS. In the present study, we identified auranofin, an orally bioavailable FDA-approved anti-rheumatic drug as a candidate repurposed drug to treat severe S. suis infections. Our results showed that auranofin can bind to the functional domain of bacterial thioredoxin reductase, decreasing the reducing redox-responsive capacity of target bacteria and allowing for the killing of S. suis cells. We also observed that auranofin has antibacterial activity against other gram-positive bacteria, such as multidrug resistant Streptococcus pneumoniae (MDRSP), Streptococcus agalactiae, and vancomycin-resistant strains of Staphylococcus aureus. Additionally, auranofin is capable of eradicating intracellular S.suis present inside infected macrophage cells. Mouse model experimental results showed that auranofin could effectively reduce the mortality of mice infected with S. suis. Compared to the ampicillin treatment group, the survival rate of mice in the auranofin treatment group in severely infected model mice was significantly improved. These results suggest that auranofin has the potential for use as an effective antibiotic against S. suis.

Nanomedical Applications of Titanium Dioxide Nanoparticles as Antibacterial Agent against Multi-Drug Resistant Streptococcus Pneumoniae

For four months (1st October 2019 to 31st January 2020), fifty sputum specimens collected from patients with suspected pneumonia in AL-Hilla General Teaching Hospital and Babylon Hospital for Pediatric and Gynecology in Babylon Province, Iraq. Only 10 isolates of Streptococcus pneumoniae were isolated and identified. Depending on the results of antibacterial susceptibility test with 16 antibiotics by disc diffusion method, S. pneumoniae isolates have multi-drug resistance. Full resistance(100%) against erythromycin, Penicillin G and Amoxicillin, full sensitivity(100%) for vancomycin and moxifloxacin, 90% for each Sulfamethoxazole/Trimethoprim and Tetracycline, 80% for each Azithromycin and Amoxicillin/Clavulanic Acid, 70% for Clindamycin, 50% for each Ceftriaxone and Chloramphenicol, 30% for Ciprofloxacin, and 20% for each Levofloxacin, Cefepime and Meropenem. By using agar-well diffusion method the antibacterial activity of Titanium Dioxide Nanoparticles (TiO2NPs) against S. pneumoniae was determined in three concentrations: 20, 30, 40 I¼g/ml. TiO2NPs exhibit significant antibacterial efficacy in all concentrations while the biggest diameter of inhibition zone was measured in the higher concentration 40 µg/ml. MIC and MBC of TiO2 Nano-particles were evaluated by using two-fold serial dilutions method, MIC ≥50 I¼g/ml while MBC ≥100 I¼g/ml. How to Cite this Article Pubmed Style Amal Talib Al-Saady and Falah H. Hussein. Applications of Titanium Dioxide Nanoparticles as Antibacterial Agent against Multi-Drug Resistant Streptococcus Pneumoniae. SRP. 2020; 11(10): 53-63. doi:10.31838/srp.2020.10.11 Web Style Amal Talib Al-Saady and Falah H. Hussein. Applications of Titanium Dioxide Nanoparticles as Antibacterial Agent against Multi-Drug Resistant Streptococcus Pneumoniae. http://www.sysrevpharm.org/?mno=9520 [Access: March 30, 2021]. doi:10.31838/srp.2020.10.11 AMA (American Medical Association) Style Amal Talib Al-Saady and Falah H. Hussein. Applications of Titanium Dioxide Nanoparticles as Antibacterial Agent against Multi-Drug Resistant Streptococcus Pneumoniae. SRP. 2020; 11(10): 53-63. doi:10.31838/srp.2020.10.11 Vancouver/ICMJE Style Amal Talib Al-Saady and Falah H. Hussein. Applications of Titanium Dioxide Nanoparticles as Antibacterial Agent against Multi-Drug Resistant Streptococcus Pneumoniae. SRP. (2020), [cited March 30, 2021]; 11(10): 53-63. doi:10.31838/srp.2020.10.11 Harvard Style Amal Talib Al-Saady and Falah H. Hussein (2020) Applications of Titanium Dioxide Nanoparticles as Antibacterial Agent against Multi-Drug Resistant Streptococcus Pneumoniae. SRP, 11 (10), 53-63. doi:10.31838/srp.2020.10.11 Turabian Style Amal Talib Al-Saady and Falah H. Hussein. 2020. Applications of Titanium Dioxide Nanoparticles as Antibacterial Agent against Multi-Drug Resistant Streptococcus Reviews in Pharmacy, 11 (10), 53-63. doi:10.31838/srp.2020.10.11 Chicago Style Amal Talib Al-Saady and Falah H. Hussein. Nanomedical Applications of Titanium Dioxide Nanoparticles as Antibacterial Agent against Multi-Drug Resistant Streptococcus Pneumoniae. Systematic Reviews in Pharmacy 11 (2020), 53-63. doi:10.31838/srp.2020.10.11 MLA (The Modern Language Association) Style Amal Talib Al-Saady and Falah H. Hussein. Nanomedical Applications of Titanium Dioxide Nanoparticles as Antibacterial Agent against Multi-Drug Resistant Streptococcus Pneumoniae. Systematic Reviews in Pharmacy 11.10 (2020), 53-63. Print. doi:10.31838/srp.2020.10.11 APA (American Psychological Association) Style Amal Talib Al-Saady and Falah H. Hussein (2020) Applications of Titanium Dioxide Nanoparticles as Antibacterial Agent against Multi-Drug Resistant Streptococcus Reviews in Pharmacy, 11 (10), 53-63. doi:10.31838/srp.2020.10.11

1582. Delafloxacin Activity Against Drug-Resistant Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, and Moraxella catarrhalis from US Medical Centers (2014–2018)

BackgroundDelafloxacin (DLX) is an anionic fluoroquinolone (FQ) antimicrobial that was approved in 2017 by the United States (US) Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections. DLX recently successfully completed a clinical trial for the treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from US hospitals participating in the SENTRY Program during 2014–2018.MethodsA total of 1,975 SPN, 1,128 HI, 684 MC, and 43 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014–2018 from US hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and CLSI (2019) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin, and tetracycline; other SPN phenotypes were LEV-NS or penicillin (PEN)-NS. β-Lactamase (BL) presence was determined for HI, HP, and MC.ResultsThe activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were similar when tested against the MDR or PEN-NS for SPN phenotypes. LEV-NS isolates had DLX MIC50/90 results of 0.12/0.25 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 2 HP isolates were BL-positive.ConclusionDLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. DLX had excellent activity against LEV-NS SPN. These data support the continued study of DLX as a potential treatment for CABP. Disclosures All authors: No reported disclosures.

Methicillin-resistant Staphylococcus aureus (MRSA) and anti-MRSA activities of extracts of some medicinal plants: A brief review.

The increasing emergence of multidrug-resistant infection causing microorganisms has become a significant burden globally. Despite the efforts of pharmaceuticals in producing relatively new antimicrobial drugs, they have resulted in a high rate of mortality, disability and diseases across the world especially in developing countries. Supporting this claim was the report of the Centre for Disease Control and Prevention (CDC) who estimated that over 2 million illnesses and 23,000 deaths per year are attributable to antibiotic resistant pathogens in the United States. They include Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-intermediate Staphylococcus aureus (VISA), Vancomycin-resistant Staphylococcus aureus (VRSA), Vancomycin-resistant enterococci (VRE), Extended spectrum beta-lactamases (ESBLs) producing gram-negative bacilli, Multidrug-resistant Streptococcus pneumoniae (MDRSP), Carbapenem-resistant Enterobacteriaceae (CRE) and Multidrug-resistant Acinetobacter baumannii. For MRSA, resistance is as a result of Methicillin-sensitive S. aureus (MSSA) strains that have acquired Staphylococcal Cassette Chromosome mec (SCCmec) which carries mecA gene. The gene encodes the penicillin-binding protein (PBP2a) which confers resistance to all β-lactam antibiotics. Vancomycin was previously the widely preferred drug for the treatment of MRSA infections. It is no longer the case with the emergence of S. aureus strains with reduced vancomycin sensitivity limiting the conventional treatment options for MRSA infections to very scanty expensive drugs. Presently, many researchers have reported the antibacterial activity of many plant extracts on MRSA. Hence, these medicinal plants might be promising candidates for treatment of MRSA infections. This work is a brief review on Methicillin-resistant Staphylococcus aureus (MRSA) and the anti-MRSA activities of extracts of selected medicinal plants.

Activity of Delafloxacin When Tested Against Bacterial Surveillance Isolates Collected in the US and Europe During 2014–2016 as Part of a Global Surveillance Program

BackgroundDelafloxacin (DLX) is an investigational anionic fluoroquinolone with an NDA that is under US FDA review to treat acute bacterial skin and skin structure infections and is undergoing Phase 3 studies to treat community-acquired bacterial pneumonia.MethodsA total of 36,683 Gram-positive (GP) and -negative (GN) bacteria isolated during 2014–2016 were selected from medical centers in the US and Europe. Susceptibility testing (S) was performed by frozen-form broth microdilution methods for DLX and comparators.ResultsDLX was very active against Staphylococcus aureus (SA, n = 9,355; MIC50/90, 0.008/0.5 mg/L) while the levofloxacin (LEV) MIC50/90 was 0.25/>4 mg/L (67.9%S). The MIC50/90 for methicillin-resistant SA (MRSA) was 0.12/1 mg/L. For MRSA, all isolates were S to vancomycin and daptomycin (DAP), linezolid and tigecycline (TGC) S was ≥99.9%. Decreased rates of S were noted for LEV (29.8%), clindamycin (72.9%), and erythromycin (17.3/17.8%; CLSI/EUCAST). Minocycline (MIC50/90, 0.12/0.25 mg/L), ceftaroline (MIC50/90, 0.25/0.5 mg/L), DAP (MIC50/90, 0.5/0.5 mg/L), and DLX (MIC50/90, 0.015/0.5 mg/L) were the most active agents tested against coagulase-negative staphylococci. Against Streptococcus pneumoniae (SPN), the MIC50/90 for DLX (0.015/0.03 mg/L) and TGC (0.03/0.06 mg/L) were the lowest among the agents tested. The DLX MIC50/90 values did not vary among the penicillin-S, -intermediate, and -R subgroups of SPN. The MIC50/90 values for DLX against S. pyogenes and S. agalactiae were 0.015/0.03 mg/L. DLX was highly active against Haemophilus influenzae. The DLX MIC50/90 (≤0.001/0.004 mg/L) was the same for β-lactamase positive and negative H. influenzae. Against Enterobacteriaceae, 76.0% of DLX MIC values were ≤1 mg/L. Susceptibility to LEV was 80.8%, and S to ceftriaxone, ceftazidime (CAZ), and cefepime ranged from 78.5–86.3%. A total of 72.6% of Pseudomonas aeruginosa isolates exhibited DLX MIC values ≤1 mg/L, while LEV S was 73.2% and CAZ was 81.6%. The MIC50/90 for both DLX and LEV were 0.5/>4 mg/L, respectively.ConclusionDLX was active against a broad range of GP and GN bacteria, including MRSA and multidrug-resistant SPN. DLX merits further study as therapy in infections in which these organisms may occur.Disclosures R. K. Flamm, Melinta Therapeutics: Research Contractor, Research grant D. Shortridge, Melinta Therapeutics: Research Contractor, Research grant M. D. Huband, Melinta Therapeutics: Research Contractor, Research grant S. McCurdy, Melinta Therapeutics: Employee, Salary M. A. Pfaller, Melinta Therapeutics: Research Contractor, Research grant

In Vivo Efficacy of Ceftaroline Fosamil in a Methicillin-Resistant Panton-Valentine Leukocidin-Producing Staphylococcus aureus Rabbit Pneumonia Model

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with broad-spectrum in vitro activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae (MDRSP), and common Gram-negative pathogens. This study investigated the in vivo activity of ceftaroline fosamil compared with clindamycin, linezolid, and vancomycin in a severe pneumonia model due to MRSA-producing Panton-Valentine leukocidin (PVL). A USA300 PVL-positive clone was used to induce pneumonia in rabbits. Infected rabbits were randomly assigned to no treatment or simulated human-equivalent dosing with ceftaroline fosamil, clindamycin, linezolid, or vancomycin. Residual bacterial concentrations in the lungs and spleen were assessed after 48 h of treatment. PVL expression was measured using a specific enzyme-linked immunosorbent assay (ELISA). Ceftaroline, clindamycin, and linezolid considerably reduced mortality rates compared with the control, whereas vancomycin did not. Pulmonary and splenic bacterial titers and PVL concentrations were greatly reduced by ceftaroline, clindamycin, and linezolid. Ceftaroline, clindamycin, and linezolid were associated with reduced pulmonary tissue damage based on significantly lower macroscopic scores. Ceftaroline fosamil, clindamycin, and, to a lesser extent, linezolid were efficient in reducing bacterial titers in both the lungs and spleen and decreasing macroscopic scores and PVL production compared with the control.

Design, Synthesis, and Biological Evaluations of Novel 7-[7-Amino-7-methyl-5-azaspiro[2.4]heptan-5-yl]-8-methoxyquinolines with Potent Antibacterial Activity against Respiratory Pathogens

Novel 7-[7-amino-7-methyl-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]- 8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 2a and 2b were designed and synthesized to obtain potent antibacterial drugs for the treatment of respiratory tract infections. Among these, compound 2a possessing (S)-configuration for the asymmetrical carbon on the pyrolidine moiety at the C-7 position of the quinolone scaffold exhibited potent in vitro antibacterial activity against respiratory pathogens including gram-positive (Streptococcus pneumoniae and Staphylococcus aureus), gram-negative (Haemophilus influenzae and Moraxcella catarrhalis), and atypical strains (Chalmydia pneumoniae and Mycoplasma pneumoniae), as well as multidrug-resistant Streptococcus pneumoniae and quinolone-resistant and methicillin-resistant Staphylococcus aureus). Furthermore, compound 2a showed excellent in vivo activity against the experimental murine pneumonia model due to multidrug resistant Streptococcus pneumoniae (MDRSP) and favorable profiles in preliminary toxicological and nonclinical pharmacokinetic studies.

Ceftaroline versus Ceftriaxone in a Highly Penicillin-Resistant Pneumococcal Pneumonia Rabbit Model Using Simulated Human Dosing

Ceftaroline (CPT) is a new cephalosporin exhibiting bactericidal activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae (MDRSP), as well as common Gram-negative pathogens. This study investigated the in vivo efficacy of a 48-hour simulated human dose regimen of CPT compared with ceftriaxone (CRO) against isolates of S. pneumoniae with different susceptibilities to penicillin in a rabbit pneumonia model. Three S. pneumoniae strains were used: CRO-susceptible penicillin-susceptible S. pneumoniae (CRO-S PSSP), CRO-susceptible penicillin-intermediate S. pneumoniae (CRO-S PISP), and CRO-resistant penicillin-resistant S. pneumoniae (CRO-R PRSP). Animals were randomized to the control group (no treatment) (n = 22) or to a group given intravenous (IV) CPT human equivalent (HE) dosage (600 mg/12 h; n = 19) or IV CRO HE dosage (1 g/24 h; n = 19). The total doses needed to achieve the HE dosage were 71 and 82 mg/kg of body weight/24 h for CRO and CPT, respectively. One group of rabbits infected with the CRO-R PRSP strain received intramuscular (IM) administration of CPT (5 or 20 mg/kg twice daily; n = 5 for each). Evaluation of efficacy was based on bacterial counts in the lungs and spleen. For IV CPT and IV CRO, the mean areas under the concentration-time curves from 0 to 24 h (AUC(0-24)s) were 155 and 938 mg · h/liter, respectively, the maximum concentrations in serum (C(max)s) were 20 and 158 mg/liter, respectively, and the minimum concentrations in serum (C(min)s) were 1.3 and 6 mg/liter, respectively. Both agents effectively treated pulmonary infections caused by CRO-S PSSP or CRO-S PISP with complete bacterial eradication in the lungs and spleen after 2 days of treatment. Against PRSP, CPT demonstrated excellent bactericidal activity, reducing bacterial counts in the lungs and spleen by approximately 8 and 4 log units, respectively (P < 0.001); CRO treatment resulted in a 2-log-unit reduction in the bacterial counts in lungs that did not reach statistical significance. Twice-daily IM CPT (5 mg/kg) reduced the bacterial burden by approximately 6 log units in the lungs and 3 log units in the spleen, and the 20-mg/kg dosage effectively eradicated PRSP infection. These findings further validate the in vivo bactericidal activity of CPT against pneumococci.

P22 Analysis of penicillin binding protein (PBP) mutations in serogroup 19 multidrug resistant Streptococcus pneumoniae (MDRSP) belonging to clonal complex 271 (CC271)

P22 Analysis of penicillin binding protein (PBP) mutations in serogroup 19 multidrug resistant Streptococcus pneumoniae (MDRSP) belonging to clonal complex 271 (CC271)

Levofloxacin for the treatment of pneumonia caused by Streptococcus pneumoniae including multidrug-resistant strains: pooled analysis

ABSTRACTObjective: To determine the clinical and microbiologic efficacy of levofloxacin for the treatment of subjects with pneumonia caused by multidrug-resistant (MDR) Streptococcus pneumoniae (MDRSP) and non-MDRSP strains.Research design and methods: A pooled analysis was conducted using data from ten clinical studies in pneumonia: five comparative studies and five noncomparative studies conducted from 1992 to 2002. This analysis included data from levofloxacin-treated subjects with S. pneumoniae isolated at study entry. Susceptibility of S. pneumoniae isolated from subjects at study entry was determined against representative agents from five antimicrobial classes: tetracyclines, sulfonamides, second-generation cephalosporins, penicillins, and macrolides. Isolates were classified as MDRSP (based on resistance to two or more antimicrobial classes) or non-MDRSP (intermediate resistance or susceptible to all classes or resistant to 1 antimicrobial class). Clinical and microbiologic efficacy of levofloxacin (i.v., p.o., or i.v./p.o. for 5 to 14 days) in the microbiologically evaluable population was determined at post-therapy; a test for homogeneity of the odds ratio of the difference in clinical success for comparative versus noncomparative studies was performed.Main outcome measures and results: The main outcome measures were clinical success rates and microbiologic eradication rates of 419 microbiologically evaluable levofloxacin-treated subjects with MDRSP or non-MDRSP. Clinical success rates were 96.3% (52/54) and 95.1% (347/365), respectively (difference −1.2; 95% confidence interval [CI]: −6.7, 4.3). Similarly, per pathogen microbiologic eradication rates for MDRSP and non-MDRSP were 96.3% (52/54) and 95.6% (350/366), respectively (difference −0.7; 95% CI: −6.1, 4.8). Study limitations include the use of data from comparative and noncomparative studies. A test for homogeneity of the odds ratios for clinical success in comparative versus noncomparative studies showed no significant difference (p = 0.27).Conclusions: These data support the use of levofloxacin for patients with community-acquired pneumonia caused by S. pneumoniae, including MDR strains.

In vitro effect of the presence of human albumin or human serum on the bactericidal activity of daptomycin against strains with the main resistance phenotypes in Gram-positives

Bactericidal activity depends on antibiotic-bacteria couples, resistance phenotype and theoretically on protein binding. This work explores the influence of protein binding on the bactericidal activity of two antibiotics, daptomycin versus vancomycin, that exhibit, respectively, different C(max) (56 versus 25.5 mg/L), protein binding (91.7% versus 36.9%) and thus theoretical free-drug fractions (4.7 versus 16.1 mg/L). The effect of the presence of physiological concentrations of human albumin (4 g/dL) or human serum (90%) on the bactericidal activity of daptomycin was studied against Gram-positive isolates with troublesome resistance phenotypes [multidrug-resistant Streptococcus pneumoniae (MDRSP), methicillin-resistant Staphylococcus aureus (MRSA), heterogeneous vancomycin-intermediate MRSA (MRSA-hVI) and vancomycin-resistant Enterococcus faecium]. Killing curves (final inocula of approximately 10(7) cfu/mL) were performed using daptomycin and vancomycin concentrations similar to the C(max) obtained in serum. Daptomycin was rapidly bactericidal (> or =3 log(10) initial inocula reduction) against S. pneumoniae and S. aureus, regardless of the strain tested or the presence of albumin or human serum (that slightly delayed bactericidal activity). Against vancomycin-susceptible or -resistant enterococci, daptomycin exhibited rapid bactericidal activity, delayed to 8 and 24 h, respectively, by human albumin. Vancomycin exhibited much slower bactericidal activity against MDRSP and methicillin-susceptible or -resistant S. aureus, but was never bactericidal against MRSA-hVI and vancomycin-susceptible or -resistant E. faecium. Daptomycin exhibited rapid bactericidal activity against the strains of the three Gram-positive species tested, regardless of resistance phenotype or the presence of physiological concentrations of albumin.

Efficacy of moxifloxacin for treatment of penicillin-, macrolide- and multidrug-resistant Streptococcus pneumoniae in community-acquired pneumonia

This pooled analysis of six prospective, multicentre trials aimed to determine the efficacy of moxifloxacin in community-acquired pneumonia (CAP) due to penicillin-, macrolide- and multidrug-resistant Streptococcus pneumoniae (MDRSP). At a central laboratory, isolates were identified and antimicrobial susceptibility determined (microbroth dilution). MDRSP was defined as resistance > or =3 drug classes. Patients received oral or sequential intravenous/oral 400 mg moxifloxacin once daily for 7-14 days. The primary endpoint was clinical success at test-of-cure for efficacy-valid patients with proven pretherapy S. pneumoniae infection. Of 140 S. pneumoniae isolated (112 respiratory, 28 blood), 23 (16.4%) were penicillin resistant, 26 (18.6%) macrolide resistant and 31 (22.1%) MDRSP. The moxifloxacin MIC90 was 0.25 microg/ml. Clinical cure with moxifloxacin was 95.4% (125/131) overall, and 100% (21/21) for penicillin-, 95.7% (22/23) for macrolide- and 96.4% (27/28) for multidrug-resistant strains. Moxifloxacin provided excellent clinical and bacteriological cure rates in CAP due to drug-resistant pneumococci.

Fluoroquinolones demonstrate in vitro activity against multi-drug resistant Streptococcus pneumoniae (MDRSP),

Fluoroquinolones demonstrate in vitro activity against multi-drug resistant Streptococcus pneumoniae (MDRSP),

Persistence of Fluoroquinolone-Resistant, Multidrug-ResistantStreptococcus pneumoniaein a Long-Term–Care Facility Efforts to Reduce Intrafacility Transmission

We describe an effort to reduce transmission of a multidrug-resistant Streptococcus pneumoniae (MDRSP) in a long-term-care facility (LTCF). Longitudinal cross-sectional study. An LTCF in New York City with ongoing disease due to an MDRSP strain among residents with AIDS since a 1995 outbreak. The MDRSP outbreak strain was susceptible to vancomycin but not to other antimicrobials tested, including fluoroquinolones. Residents and staff members of the LTCF during 1999 through 2001. Implementing standard infection control measures, and developing and implementing "enhanced standard" infection control measures, modified respiratory droplet prevention measures to reduce inter-resident transmission. Before the intervention, nasopharyngeal carriage of the MDRSP outbreak strain was detected in residents with AIDS and residents with tracheostomies who were not dependent on mechanical ventilation. The prevalence of nasopharyngeal carriage of the MDRSP outbreak strain was 7.8% among residents who had AIDS and 14.6% among residents with tracheostomies. After training sessions on standard and enhanced standard infection control measures, the staff appeared to have good knowledge and practice of the infection control measures. After the intervention, new transmission among residents with tracheostomies was prevented; however, these residents were prone to persistent tracheal carriage and needed ongoing enhanced standard infection control measures. Ongoing transmission among residents with AIDS, a socially active group, was documented, although fewer cases of disease due to the outbreak strain occurred. Infection control contributed to less transmission of MDRSP in the LTCE Additional strategies are needed to reduce transmission and carriage among certain resident populations.

Failure to Control an Outbreak of Multidrug-ResistantStreptococcus pneumoniaein a Long-Term–Care Facility Emergence and Ongoing Transmission of a Fluoroquinolone-Resistant Strain

To characterize risk factors associated with pneumococcal disease and asymptomatic colonization during an outbreak of multidrug-resistant Streptococcus pneumoniae (MDRSP) among AIDS patients in a long-term-care facility (LTCF), evaluate the efficacy of antimicrobial prophylaxis in eliminating MDRSP colonization, and describe the emergence of fluoroquinolone resistance in the MDRSP outbreak strain. Epidemiologic investigation based on chart review and characterization of SP strains by antimicrobial susceptibility testing and PFGE and prospective MDRSP surveillance. An 80-bed AIDS-care unit in an LTCF PARTICIPANTS: Staff and residents on the unit. From April 1995 through January 1996, 7 cases of MDRSP occurred. A nasopharyngeal (NP) swab survey of all residents (n=65) and staff (n=70) detected asymptomatic colonization among 6 residents (9%), but no staff. Isolates were sensitive only to rifampin, ofloxacin, and vancomycin. A 7-day course of rifampin and ofloxacin was given to eliminate colonization among residents: NP swab surveys at 1, 4, and 10 weeks after prophylaxis identified 1 or more colonized residents at each follow-up with isolates showing resistance to one or both treatment drugs. Between 1996 and 1999, an additional 6 patients were diagnosed with fluoroquinolone-resistant (FQ-R) MDRSP infection, with PFGE results demonstrating that the outbreak strain had persisted 3 years after the initial outbreak was recognized. Chemoprophylaxis likely contributed to the development of a FQ-R outbreak strain that continued to be transmitted in the facility through 1999. Long-term control of future MDRSP outbreaks should rely primarily on vaccination and strict infection control measures.

Gatifloxacin

Gatifloxacin (Tequin) is an 8-methoxy fluoroquinolone approved in the US for use in the treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), acute sinusitis, uncomplicated and complicated urinary tract infections (UTIs), pyelonephritis, gonorrhoea and uncomplicated skin and skin structure infections. Gatifloxacin has a broad spectrum of antibacterial activity in vitro and good clinical and bacteriological efficacy in patients with indicated infections following once-daily administration by the intravenous or oral routes. It is generally well tolerated; the most common adverse events are associated with the gastrointestinal tract and CNS. Recent approvals for the use of gatifloxacin in the treatment of CAP due to multidrug-resistant Streptococcus pneumoniae (MDRSP) and in uncomplicated skin and skin structure infections extend the role of this drug in the treatment of bacterial infections in the US.