zithromax and Klebsiella-Infections

This was a randomized, third-party-blinded, multicenter study that compared once-daily azithromycin (500 mg on day 1, followed by 250 mg on days 2-5) to cefaclor (500 mg three times daily for 10 days) in the treatment of patients with acute bronchitis or pneumonia. A total of 546 patients were entered into the study and 272 patients were evaluable for efficacy analysis. Of these, 249 (176 azithromycin, 73 cefaclor) had bronchitis and 23 (15 azithromycin, 8 cefaclor) had pneumonia. The combined clinical cure and improvement rate, as determined by the investigator, was 96% for azithromycin and 94% for cefaclor, with 88% bacteriologic eradication in both treatment groups. The elimination of Haemophilus influenzae was significantly better with azithromycin (94.5%) than with cefaclor (61.1%) (p less than 0.001; Fisher's exact two-tail test). The two antibiotics were well tolerated during this study; the incidence of side effects reported was similar for azithromycin and cefaclor. Approximately two thirds of the side effects were mild. Only minor abnormalities in the screening laboratory tests were noted. This study shows that a 5-day course of once-daily azithromycin is as effective as a 10-day three times daily course of cefaclor in the treatment of patients with acute lower respiratory tract infections.

Topics: Azithromycin; Bronchitis; Cefaclor; Erythromycin; Haemophilus Infections; Humans; Klebsiella Infections; Moraxella catarrhalis; Neisseriaceae Infections; Pneumonia; Prospective Studies; Sputum; Staphylococcal Infections; Streptococcal Infections

Novel antibiotic combinations may act synergistically to inhibit the growth of multidrug-resistant bacterial pathogens but predicting which combination will be successful is difficult, and standard antimicrobial susceptibility testing may not identify important physiological differences between planktonic free-swimming and biofilm-protected surface-attached sessile cells. Using a nominally macrolide-resistant model Klebsiella pneumoniae strain (ATCC 10031) we demonstrate the effectiveness of several macrolides in inhibiting biofilm growth in multi-well plates, and the ability of azithromycin (AZM) to improve the effectiveness of the antibacterial last-agent-of-choice for K. pneumoniae infections, colistin methanesulfonate (CMS), against biofilms. This synergistic action was also seen in biofilm tests of several K. pneumoniae hospital isolates and could also be identified in polymyxin B disc-diffusion assays on azithromycin plates. Our work highlights the complexity of antimicrobial-resistance in bacterial pathogens and the need to test antibiotics with biofilm models where potential synergies might provide new therapeutic opportunities not seen in liquid culture or colony-based assays.

Topics: Anti-Bacterial Agents; Azithromycin; Biofilms; Colistin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Mesylates; Microbial Sensitivity Tests; Pneumonia; Polymyxin B

In this study, an IncI1 plasmid encoding resistance to both cefotaxime and azithromycin was recovered from a clinical Klebsiella pneumoniae strain. The azithromycin resistance was confirmed to be mediated by the

Topics: Anti-Bacterial Agents; Azithromycin; beta-Lactamases; Cefotaxime; Drug Resistance, Multiple, Bacterial; Escherichia coli; Gene Transfer, Horizontal; Humans; Klebsiella Infections; Klebsiella pneumoniae; Methyltransferases; Microbial Sensitivity Tests; Plasmids; Salmonella

Topics: Acinetobacter Infections; Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Azithromycin; Bacteremia; Candidemia; COVID-19 Drug Treatment; Enzyme Inhibitors; Female; Gram-Negative Bacterial Infections; Humans; Hydroxychloroquine; Italy; Klebsiella Infections; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pneumonia, Ventilator-Associated; Protective Factors; Pseudomonas Infections; Respiration, Artificial; SARS-CoV-2; Staphylococcal Infections; Superinfection; Teicoplanin

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Antifungal Agents; Antimicrobial Stewardship; Aspergillosis; Azithromycin; Bacterial Infections; Cohort Studies; Coinfection; COVID-19; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Germany; Humans; Klebsiella Infections; Linezolid; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Retrospective Studies; SARS-CoV-2; Staphylococcal Infections; Streptococcal Infections; Sulbactam; Vancomycin; Young Adult

Trans-translation is a unique bacterial ribosome rescue system that plays important roles in the tolerance to environmental stresses. It is composed of an ssrA-encoded tmRNA and a protein SmpB. In this study, we examined the role of trans-translation in antibiotic tolerance in Klebsiella pneumoniae and explored whether the inhibition of this mechanism could enhance the bactericidal activities of antibiotics. We found that deletion of the ssrA gene reduced the survival of K. pneumoniae after treatment with kanamycin, tobramycin, azithromycin, and ciprofloxacin, indicating an important role of the trans-translation in bacterial antibiotic tolerance. By using a modified ssrA gene with a 6×His tag we demonstrated that tobramycin suppressed the azithromycin and ciprofloxacin-elicited activation of trans-translation. The results were further confirmed with a trans-translation reporter system that is composed of a normal mCherry gene and a gfp gene without the stop codon. Compared to each individual antibiotic, combination of tobramycin with azithromycin or ciprofloxacin synergistically enhanced the killing activities against planktonic K. pneumoniae cells and improved bacterial clearance in a murine cutaneous abscess infection model. In addition, the combination of tobramycin and ciprofloxacin increased the bactericidal activities against biofilm-associated cells. Overall, our results suggest that the combination of tobramycin with azithromycin or ciprofloxacin is a promising strategy in combating K. pneumoniae infections.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Biofilms; Ciprofloxacin; Codon; Dogs; Drug Resistance, Microbial; Drug Synergism; Humans; Klebsiella Infections; Klebsiella pneumoniae; Luminescent Proteins; Microbial Sensitivity Tests; Red Fluorescent Protein; Tobramycin

Ozena, or atrophic rhinitis, is a chronic nasal process seen in Africa, India, and the Middle East. It is marked by the triad of fetid nasal discharge, crusting, and atrophy, and is often associated with Klebsiella infection. We present cases of ozena with nasal Klebsiella in three unrelated patients, including two east African children and one Saudi adult. All three patients grew Klebsiella species in culture and required prolonged treatment with multiple methodologies, including antibiotics, saline rinses, and surgical debridement. They differed greatly in time from presentation to diagnosis, and demonstrated various stages of the disease process. Ozena is rarely seen in the United States, and when it is seen, it is often misdiagnosed. Lack of prompt, adequate treatment can lead to long-term sequelae such as obliteration of nasal architecture, anosmia, sinus and skull base destruction, and social disenfranchisement due to the extreme foul smell of the nasal discharge. Clinicians should maintain a high index of suspicion for primary atrophic rhinitis when presented with its classic symptoms. Culture-directed and prolonged therapy with appropriate follow-up is a necessary component of a successful treatment plan.

Topics: Aged; Amoxicillin; Azithromycin; Child; Clavulanic Acid; Drug Resistance, Multiple, Bacterial; Emigrants and Immigrants; Ethiopia; Female; Gentamicins; Humans; Infant; Klebsiella; Klebsiella Infections; Male; Nose; Refugees; Rhinitis, Atrophic; Saudi Arabia; Somalia; Treatment Outcome

Enterobacteriaceae, carrying the New Delhi metallo-β-lactamase-1 (NDM-1) gene (bla (NDM-1)), have emerged and posed a threat since 2006. In Japan, bla (NDM-1)-carrying Escherichia coli was first described in 2010. In this study, we characterized NDM-1-positive Klebsiella pneumoniae strain 419 in Japan, which was isolated from the urine of a 90-year-old Japanese patient who had never been to the Indian subcontinent. K. pneumoniae 419 belonged to ST42. It possessed a surface capsule (with untypeable capsular PCR types) and was resistant to serum killing. K. pneumoniae 419 cells were occasionally flagellated or piliated and autoaggregated. K. pneumoniae 419 was resistant to β-lactams (including carbapenems), aminoglycosides, and fluoroquinolones, and was susceptible to imipenem (or biapenem), aztreonam, polymixin B, and colistin. It possessed at least eight plasmids; of those, a 74-kb plasmid (pKPJ1) of the replicon FIIA carried bla (NDM-1) and was conjugally transferred to E. coli strains, with a 71-kb transferable azithromycin-resistant (mphA (+)) plasmid of the replicon F (pKPJ2), as a large (145-kb) plasmid (pKPJF100) through a transposition event. In addition to bla (NDM-1), pKPJ1 carried arr-2, pKPJ2 carried mphA, and pKPJF100 carried both. They were negative for the 16S rRNA methylase gene, e.g., which is frequently associated with bla (NDM-1). The data demonstrate that K. pneumoniae 419 possessed virulence- and fitness-associated surface structures, was resistant to serum killing, and possessed a unique (or rare) genetic background in terms of ST type and bla (NDM-1)-carrying plasmid.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; beta-Lactam Resistance; beta-Lactamases; Blood Bactericidal Activity; Conjugation, Genetic; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Japan; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Microscopy, Electron; Plasmids; Urinary Tract Infections; Urine

L-701,677, L-708,299 and L-708,365 are novel azalide derivatives of erythromycin that exhibit improved acid stability over erythromycin, azithromycin and clarithromycin. The half-life in aqueous solution at pH = 2.1 of these compounds ranged from 0.3 hour for erythromycin to 16.2 hours for L-708,299. The rank order of half-life in acid solution from most to least stable was L-708,299 > L-701,677 > L-708,365 > azithromycin = clarithromycin > erythromycin. In a disseminated Streptococcus pyogenes mouse infection model, azithromycin and L-708,365 were slightly more efficacious than clarithromycin, L-701,677 and L-708,299; all 5 compounds being more active than erythromycin. In a Klebsiella pneumoniae pulmonary challenge mouse model, azithromycin, L-701,677, L-708,299 and L-708,365 were all equal in efficacy and at least four-fold more active than clarithromycin and erythromycin. Clarithromycin, L-708,365 and interestingly erythromycin, showed greater bacterial clearance than azithromycin, L-701,677 and L-708,299 in a localized infection model that measured clearance of Staphylococcus aureus from mouse thigh tissues. Our results indicate that L-701,677, L-708,299 and L-708,365 exhibit improved acid stability and were at least equally efficacious as presently marketed macrolide/azalide antibiotics.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Clarithromycin; Drug Evaluation, Preclinical; Drug Stability; Erythromycin; Female; Half-Life; Klebsiella Infections; Macrolides; Mice; Mice, Inbred DBA; Molecular Structure; Staphylococcal Infections; Streptococcal Infections