Objective: This paper demonstrated the effectiveness of intrastromal injection of levofloxacin 1.5% ophthalmic solution in the management of recalcitrant Gram-positive bacterial keratitis. Methods: This is a report on two cases of recalcitrant bacterial keratitis encountered at the External Diseases and Cornea Clinic of the Department of Ophthalmology and Visual Sciences at the Philippine General Hospital. Results: Two middle-aged females presented with bacterial keratitis unresponsive to previous antibiotic treatment with impending corneal perforation. The Gram stain of the corneal scraping in the first case revealed Gram-positive cocci, while the second case showed encapsulated Gram-positive bacilli and encapsulated Grampositive cocci in chains. In both cases, repeated intrastromal injections of levofloxacin 1.5% in addition to increasing the frequency of topical levofloxacin 1.5% resulted in marked improvement in visual acuity and resolution of deep stromal infiltrates and hypopyon. Conclusion These cases highlighted the utility of intrastromal levofloxacin 1.5% ophthalmic solution in the management of recalcitrant Gram-positive bacterial keratitis.
Fluoroquinolones ; Levofloxacin

Humans ; Mycobacterium tuberculosis/genetics* ; Microspheres ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Fluoroquinolones ; Drug Resistance, Bacterial/genetics* ; Tuberculosis, Multidrug-Resistant/microbiology*

Purpose: This study compared the safety outcomes of two intracameral fluoroquinolone antibiotics, moxifloxacin and levofloxacin, as prophylaxis treatment in eyes that underwent uncomplicated cataract surgery. Methods: This is a prospective, double-masked, randomized, interventional, single-center clinical trial. Eyes with visually-significant cataracts underwent phacoemulsification and received preservative-free intracameral 0.5% moxifloxacin [58 eyes (M group)] or 0.5% levofloxacin [56 eyes (L group)] at the end of the surgery as antibiotic prophylaxis. The following safety parameters were evaluated postoperatively at Day 1, Week 1 and Month 1: central retinal thickness (CRT), macular volume (MV), central corneal thickness (CCT), and endothelial cell density (ECD). In-between group comparison was made at each of the 4 study visits using Student’s t-test. Results: Both M and L groups had similar baseline characteristics. There were no significant differences in CRT, MV, CCT and ECD between the 2 groups at each time point in the study. There were no significant differences in the mean changes in CRT, MV, CCT and ECD from baseline to final visit between the 2 groups. No study-related adverse events were observed during the study period. Conclusion Intracameral application of preservative-free 0.5% moxifloxacin and 0.5% levofloxacin appear to have similar safety outcomes when used as antibacterial prophylaxis among eyes undergoing cataract surgery. Based on the results, both fluoroquinolone agents are potentially suitable options for endophthalmitis chemoprophylaxis.
Levofloxacin ; Moxifloxacin ; Fluoroquinolones

BACKGROUND: Long-term administration of ethambutol (EMB) for Mycobacterium avium complex lung disease (MAC-LD) sometimes leads to permanent discontinuation of EMB due to various adverse events. This study aimed to investigate treatment outcomes after discontinuation of EMB.METHODS: Among patients diagnosed with MAC-LD between January 2001 and December 2014, 508 patients whose treatment was initiated with standard regimen until May 2018 were enrolled at a tertiary referral center in Korea. Of these 508 patients, 60 (11.8%) discontinued EMB due to various adverse effects. Among these 60 patients, treatment outcomes were analyzed for 44 patients by comparing their outcomes with those of matched subjects who received the standard treatment regimen without EMB discontinuation.RESULTS: The mean age of the 60 patients who discontinued EMB was 64.4 years. Ocular toxicity was the most common cause of discontinuation of EMB (75.0%, 45/60). The mean duration of EMB administration before its discontinuation was 7.0 ± 4.6 months. The treatment failure rate of the 44 patients with EMB discontinuation analyzed for treatment outcome was 29.6%, which was higher than that of the matched patients who received the standard regimen (18.3%), although the difference was not significant (P = 0.095). Of these 44 patients, EMB was substituted with later-generation fluoroquinolone in 23 patients, and the treatment failure rate of these 23 patients was significantly higher than that of the matched patients who received the standard regimen (39.1% vs. 19.3%, P = 0.045).CONCLUSION: These findings suggest that treatment outcomes are unsatisfactory in patients with MAC-LD who discontinue EMB owing to adverse events. Notably, there was a statistically significant high failure rate in patients who were prescribed fluoroquinolone to replace EMB.
Ethambutol ; Fluoroquinolones ; Humans ; Korea ; Lung Diseases ; Mycobacterium avium Complex ; Mycobacterium avium ; Mycobacterium ; Tertiary Care Centers ; Treatment Failure ; Treatment Outcome

Increasing resistance due to the production of extended-spectrum β-lactamase (ESBL) in Escherichia coli is a major problem to public health and CTX-M enzymes have become the most prevalent ESBL worldwide. In this study, resistance profiles of E. coli isolated in Korea and the genetic environments of bla(CTX-M) genes were analyzed by PCR and direct sequencing to clarify the mechanisms of spread of CTX-M. Resistance rates of CTX-M-producing E. coli, including β-lactams, fluoroquinolones and aminoglycosides, were significantly higher than that of CTX-M-non-producers (p<0.01). Of 41 tested, 39 (95.1%) isolates of CTX-M-producing E. coli showed resistance transfer by conjugation. All the transconjugants harboured large plasmids of 118~172 megadalton. Insertion sequence ISEcp1B was detected in the upstream of the bla(CTX-M) in 38 (92.7%) isolates with bla(CTX-M). ISEcp1B was disrupted by IS26 in 16 (39.0%) isolates with bla(CTX-M). ISEcp1B carried −35 and −10 promoter components between right inverted repeat (IRR) and the start codon of bla(CTX-M). orf477 or IS903D was observed in the downstream of the bla(CTX-M) in all the isolates with bla(CTX-M-3/15/55) or with bla(CTX-M-14/27), respectively. Sequence similar to IRR of ISEcp1B was located downstream of orf477. Target duplication sequences were detected both upstream of IRL and downstream of IRR. These results showed the involvement of ISEcp1B in the mobilization of the resistance genes. In conclusion, the surrounding DNAs of bla(CTX-M) genes were very diverse, and the spread and the expression of CTX-M may be deeply related with ISEcp1B. These informations will provide important knowledge to control the increase in CTX-M-ESBLs.
Aminoglycosides ; Codon, Initiator ; DNA ; Escherichia coli ; Escherichia ; Fluoroquinolones ; Korea ; Plasmids ; Polymerase Chain Reaction ; Public Health

The persistent antibiotics resistant issue has emerged as an influencing factor to deteriorate community health. So, new antibiotics development is urgent for the treatment of bacterial infections. Alternatively, delafloxacin is an eminent new fluoroquinolone, and chemically distinct from older fluoroquinolones. There is lack of proton substituent that indicates the poor acidic property of the drug. It also has a good intracellular penetration capacity that increases the intensity of the bactericidal property in acidic environment. Delafloxacin is a super active drug against the skin and soft tissue infections (SSTIs) and community-acquired respiratory tract infections. Delafloxacin also exhibits better efficacy against pathogens which are resistant to other fluoroquinolones, such as methicillin-resistant Staphylococcus aureus (MRSA). Delafloxacin received approval from the US Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSI). Phase III clinical trial among patients with community-acquired pneumonia (CAP) is ongoing to evaluate the effectiveness of delafloxacin. From the aforementioned arguments, delafloxacin will be a prominent candidate for the upcoming antibacterial agent. Similarly, delafloxacin can be a crucial drug to fight against ABSSI.
Anti-Bacterial Agents ; Bacterial Infections ; Fluoroquinolones ; Humans ; Methicillin-Resistant Staphylococcus aureus ; Pneumonia ; Protons ; Respiratory Tract Infections ; Skin ; Soft Tissue Infections ; United States Food and Drug Administration

It is crucial to optimize the dose of fluoroquinolones to avoid antibiotic resistance and to attain clinical success. We undertook this study to optimize the dose of enrofloxacin against Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) in chicken by assessing its pharmacokinetic/pharmacodynamic (PK/PD) indices. The antibacterial activities of enrofloxacin against S. Enteritidis were evaluated. After administering 10 mg/kg body weight (b.w.) of enrofloxacin to broiler chickens of both sexes by intravenous (IV) and peroral (PO) routes, blood samples were drawn at different intervals and enrofloxacin concentrations in plasma were determined. PK/PD indices were calculated by integrating the PK and PD data. The elimination half-lives (T(1/2)), time required to reach peak concentration (T(max)), peak concentration (C(max)), and area under curve (AUC) after administering enrofloxacin by PO and IV routes were 25.84 ± 1.40 h, 0.65 ± 0.12 h, 3.82 ± 0.59 µg/mL, and 20.84 ± 5.0 µg·h/mL, and 12.84 ± 1.4 h, 0.22 ± 0.1 h, 6.74 ± 0.03 µg/mL, and 21.13 ± 0.9 µg.h/mL, respectively. The bioavailability of enrofloxacin was 98.6% ± 8.9% after PO administration. The MICs of enrofloxacin were 0.0625–1 µg/mL against S. Enteritidis strains, and the MIC₅₀ was 0.50 µg/mL. The C(max)/MIC₅₀ were 7.64 ± 0.2 and 13.48 ± 0.7 and the 24 h AUC/MIC₅₀ were 41.68 ± 0.1 and 42.26 ± 0.3 after administering the drug through PO and IV routes, respectively. The data in this study indicate that the application of 50 mg/kg b.w. of enrofloxacin to chicken through PO and IV routes with a dosing interval of 24 h can effectively cure S. Enteritidis infection, indicating the need for a 5-fold increase in the recommended dosage of enrofloxacin in chicken.
Area Under Curve ; Biological Availability ; Body Weight ; Chickens ; Drug Resistance, Microbial ; Fluoroquinolones ; Pharmacokinetics ; Plasma ; Salmonella enterica ; Salmonella enteritidis ; Salmonella ; Serogroup

Isolates of 24 enterococci, 5 Enterococcus casseliflavus and 19 Enterococcus gallinarum, possessing vanC genes and showing low-level resistance to vancomycin were obtained from mice from commercial mouse breeding companies. Since some of these isolates showed resistance to other antibiotics, the purpose of this study was to clarify the resistant profiles of these isolates. One E. casseliflavus isolate showed resistance to erythromycin with a minimal inhibitory concentration (MIC) of 8 μg/mL and also showed apparent resistance to fluoroquinolones with an MIC of 32 μg/mL for ciprofloxacin. The MICs of 2 other fluoroquinolone-resistant E. casseliflavus and E. gallinarum isolates were 3 and 6 μg/mL, respectively. These 3 resistant isolates showed an absence of macrolide- and fluoroquinolone-resistant genes, including amino acid substitutions in the quinolone resistance determining regions of DNA gyrase and topoisomerase IV. Resistance to tetracycline was detected in 2 E. gallinarum isolates that were highly resistant, exhibiting MICs of 48 and 64 μg/mL and possessing tet(O) genes. The results indicate that antibiotic-resistant enterococci are being maintained in some laboratory mouse strains that have never been treated with an antibiotic.
Amino Acid Substitution ; Animals ; Anti-Bacterial Agents ; Breeding ; Ciprofloxacin ; DNA Gyrase ; DNA Topoisomerase IV ; Drug Resistance, Microbial ; Enterococcus ; Erythromycin ; Fluoroquinolones ; Mice ; Tetracycline ; Vancomycin

Although Mycoplasma pneumoniae pneumonia (MPP) has been generally susceptible to macrolides, the emergence of macrolide-resistant MPP (MRMP) has made its treatment challenging. MRMP rapidly spread after the 2000s, especially in East Asia. MRMP is more common in children and adolescents than in adults, which is likely related to the frequent use of macrolides for treating M. pneumoniae infections in children. MRMP is unlikely to be related to clinical, laboratory, or radiological severity, although it likely prolongs the persistence of symptoms and the length of hospital stay. Thereby, it causes an increased burden of the disease and poor quality of life for the patient as well as a societal socioeconomic burden. To date, the only alternative treatments for MRMP are secondary antimicrobials such as tetracyclines (TCs) or fluoroquinolones (FQs) or systemic corticosteroids; however, the former are contraindicated in children because of concerns about potential adverse events (i.e., tooth discoloration or tendinopathy). A few guidelines recommended TCs or FQs as the second-line drug of choice for treating MRMP. However, there have been no evidence-based guidelines. Furthermore, safety issues have not yet been resolved. Therefore, this article aimed to review the benefits and risks of therapeutic alternatives for treating MRMP in children and review the recommendations of international or regional guidelines and specific considerations for their practical application.
Adolescent ; Adrenal Cortex Hormones ; Adult ; Child ; Drug Resistance ; Far East ; Fluoroquinolones ; Humans ; Length of Stay ; Macrolides ; Mycoplasma pneumoniae ; Mycoplasma ; Pneumonia ; Pneumonia, Mycoplasma ; Quality of Life ; Risk Assessment ; Tetracycline ; Tetracyclines ; Tooth Discoloration

Antibacterial drugs are one of the most important therapeutic agents of bacterial infections but multidrug resistant Escherichia coli (MDREC) is an increasing problem worldwide. Major resistance mechanism of MDREC is horizontal gene transfer of R plasmids harboring integrons, which the integron integrase (IntI) catalyzes gene cassette insertion and excision through site specific recombination. In this study, resistance profiles of integron harboring E. coli isolated in Korea and the genetic environments of integron gene cassettes were analyzed by PCR and direct sequencing to clarify the mechanisms of spread of integron harboring E. coli. Resistance rates of integron harboring E. coli, including β-lactams, aminoglycosides, and fluoroquinolones and MDR frequencies were significantly higher than that of E. coli without integron (p < 0.01). Majority (80%) of integron harboring E. coli showed resistance transfer by conjugation. Most (80%) of E. coli had dfrA17-aadA5 cassette array and PcH1 hybrid promoter; 16.7% of E. coli had dfrA12-orfF-aadA2 cassette array and PcW promoter. The higher prevalence of weak Pc variants among most (96.7%) of integron harboring MDREC suggests that a flexible cassette array is more important than enhanced expression. All the integrons had LexA binding motif suggests that SOS responses control the expression of these integrons. In conclusion, the genetic bases of integrons were diverse, and the spread and the expression of prevalent gene cassette arrays may be deeply related with strengths of Pc promoters in integrons. These informations will provide important knowledge to control the increase of integron harboring MDREC.
Aminoglycosides ; Bacterial Infections ; Escherichia coli ; Escherichia ; Fluoroquinolones ; Gene Transfer, Horizontal ; Integrases ; Integrons ; Korea ; Polymerase Chain Reaction ; Prevalence ; R Factors ; Recombination, Genetic ; SOS Response (Genetics)