In vitro activities of sitafloxacin (STFX) along with fluoroquinolones (levofloxacin (LVFX), moxifloxacin (MFLX), garenoxacin (GRNX)) and macrolides (azithromycin, clarithromycin) against atypical bacteria (Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia trachomatis, Chlamydophila pneumoniae) recovered from clinical specimens from 2009 to 2014 at different healthcare facilities in Japan were investigated. The minimum inhibitory concentration of STFX at which 90% of isolates (MIC₉₀) against M pneumoniae (n= 14) was 0.03μg/mL which was comparable to GRNX, 4- and 16-fold more active than MFLX and LVFX, respectively. Reduced susceptibilities of M pneumoniae (9/14 isolates) to macrolides were observed. MIC₉₀ of STFX against L. pneumophila (n =15) was 0.004μg/mL which was 2- and 4-fold more active than GRNX/LVFX and MFLX, respectively. The minimum inhibitory concentration range of STFX against C. trachomatis (n=5) and C. pneumoniae (n=5) were from 0.015 to 0.03 and from 0.03 to 0.06μg/mL, respectively. Furthermore, differences between the activities of STFX against various clinical isolates in 2009 and those in 2012, which were already published in two articles (Jpn. J. Antibiotics 63:411- 430, 2010, 66:311-330, 2013), were also evaluated. The MIC90s of STFX against methicillin- susceptible Staphylococcus aureus (MSSA), Streptococcus spp. and Enterococcus faecalis isolated in 2012 were 4 or 8 times higher than those in 2009, however there was no difference between STFX activities against other species in 2009 and those in 2012. In conclusion, STFX showed potent activity against atypical bacteria (M pneumoniae, L. pneumophila, C. trachomatis, C. pneumoniae) and no tendency for emergence resistance to Gram- positive cocci, Gram-negative bacteria and anaerobes except MSSA, Streptococcus spp. andt. faecalis.

The lack of available antibiotics is a global public health problem due to the emergence of antimicrobial resistance. Effective therapeutic regimens are urgently needed against Escherichia coli that produces colistin-resistance gene mcr-1 and to inhibit the emergence of resistance. In this study, we assessed the antimicrobial activity of a series of concentrations of colistin-based combinations with rifampin and/or azithromycin against three strains of Escherichia coli, including colistin-resistant isolate MZ1501R, HE1704R that produces MCR-1, and colistin-susceptible isolate MZ1509S Experiments were conducted at a medium inoculum of ∼107 CFU/mL over 48 h. Subsequently, the in vivo therapeutic effect was investigated using a neutropenic thigh-infected mouse model. Almost all monotherapies showed unsatisfactory antibacterial activity against E. coli isolates producing MCR-1. By contrast, colistin in combination with rifampin or azithromycin resulted in an obvious decrease in bacterial burden, albeit with regrowth. More obviously, synergistic antimicrobial activity of colistin-based triple combination therapy with rifampin and azithromycin was observed, resulting in a rapid and exhaustive antibacterial effect. In vivo treatments confirmed these findings where a mean decrease of 0.38 to 0.90 log10 CFU and 1.27 to 1.78 log10 CFU was noted after 24 h and 48 h of treatment, respectively, against colistin-resistant E. coli strains when 5 mg/kg colistin was combined with rifampin and azithromycin. Colistin-based combinations with rifampin and azithromycin provide a more active therapeutic regimen than monotherapy or colistin-based double combinations against E. coli producing MCR-1.

Recently, mobile phones have become a potent vector for the transmission of pathogens. In hospitals, the use of the mobile phones by healthcare workers in an unhygienic manner accelerates the spread of nosocomial infection. We aimed to investigate the prevalence of microbiological contamination of mobile phones belonging to clinicians in Bangladesh hospitals. From 100 samples, we identified 69 isolates of bacteria including 22 Staphylococcus aureus; 11 Pseudomonas aeruginosa; 14 Escherichia coli; 6 Salmonella typhi 6 and 16 Staphylococcus epidermidis. On the basis of antibiotic susceptibility test using 11 antibiotics, it has been observed that most of the isolated bacteria became resistant to antibiotics and compared to other isolates, isolates of S. epidermidis and S. typhi were more resistant and sensitive, respectively. About 68.8% isolates showed that their resistance capacities against ampicillin but in contrast, 56.6% isolated were susceptible to imipenem. Azithromycin and imipenem against S. aureus, gentamicin against P. aeruginosa, tetracycline and imipenem against E. coli, tetracycline against S. typhi, and S. epidermidis revealed significant antimicrobial affectivity. We found that mobile phones are potential vectors to spread antibiotic-resistant nosocomial pathogens. Based on the study, an effective disinfection practice for cellular phones used in hospitals should be introduced to prevent the potential of cross-contamination.

The Food and Drug Administration (FDA) has recently included a black box warning on fibromyalgia like symptoms with fluoroquinolones (FQs) but no large epidemiologic study is to date available. We undertook a case-control study using a random sample of 9,053,240 subjects obtained from the PharMetrics Plus health claims database in the United States. Cases received at least two fibromyalgia diagnoses coded by a rheumatologist matched to a ten randomly selected controls. After identifying 5,148 cases of fibromyalgia and 51,480 controls, the adjusted rate ratio of fibromyalgia for use of any fluoroquinolones, amoxicillin, and azithromycin were 1.63 (95% CI:1.41-1.87), 1.64 (95% CI: 1.46-1.85), and 1.68 (95% CI, 1.49-1.89) respectively. The adjusted RR for any use of FQ compared to any use of amoxicillin or azithromycin was 0.99 (95% CI:0.83-1.18) and azithromycin is 0.97 (95%CI:0.82-1.16) respectively. The risk of fibromyalgia with FQs is similar to that with amoxicillin and azithromycin.

The present study aimed to discuss and compare the effects and expenses of different antibiotic regimens in the treatment of lower respiratory tract infection (LRTI). A retrospective analysis was performed on 200 patients diagnosed with LRTI and treated at the Department of Respiratory Medicine of Dongying People's Hospital from February 2015 to May 2017. The patients were randomly divided into Group A, Group B, Group C and Group D, with 50 cases in each group, and were treated with ceftriaxone sodium, ceftizoxime sodium, levofloxacin and azithromycin, respectively. Venous blood of patients was collected. White blood cells (WBC) of venous blood were detected using a hematology analyzer and C-reactive protein (CRP) was tested with latex immunoturbidimetry. Moreover, therapeutic effects and drug costs of four different antibiotics were compared. No adverse reactions occurred to patients in the four groups during the treatment process. The value at each time point after treatment was significantly decreased compared with that at the previous time point before treatment within the group (P<0.01). The treatment expenses of patients in Group A, Group B and Group D were significantly increased compared with those in Group C (P<0.01), the treatment expenses of patients in Group B and Group D were significantly increased compared with those in Group A (P<0.01) and the treatment expenses of patients in Group D were significantly increased compared with those in Group B (P<0.01). Ceftriaxone sodium, ceftizoxime sodium, levofloxacin and azithromycin all have a good antimicrobial efficacy. The treatment condition of LRTI can be dynamically monitored by WBC and CRP which can accurately reflect the progression condition of patients' illness and the treatment effect. In economic terms, the treatment cost of levofloxacin is the lowest; thus, it is worthy of clinical popularization and application.

SUMMARYPrimary Toxoplasma gondii infection is usually subclinical, but cervical lymphadenopathy or ocular disease can be present in some patients. Active infection is characterized by tachyzoites, while tissue cysts characterize latent disease. Infection in the fetus and in immunocompromised patients can cause devastating disease. The combination of pyrimethamine and sulfadiazine (pyr-sulf), targeting the active stage of the infection, is the current gold standard for treating toxoplasmosis, but failure rates remain significant. Although other regimens are available, including pyrimethamine in combination with clindamycin, atovaquone, clarithromycin, or azithromycin or monotherapy with trimethoprim-sulfamethoxazole (TMP-SMX) or atovaquone, none have been found to be superior to pyr-sulf, and no regimen is active against the latent stage of the infection. Furthermore, the efficacy of these regimens against ocular disease remains uncertain. In multiple studies, systematic screening for Toxoplasma infection during gestation, followed by treatment with spiramycin for acute maternal infections and with pyr-sulf for those with established fetal infection, has been shown to be effective at preventing vertical transmission and minimizing the severity of congenital toxoplasmosis (CT). Despite significant progress in treating human disease, there is a strong impetus to develop novel therapeutics for both the acute and latent forms of the infection. Here we present an overview of toxoplasmosis treatment in humans and in animal models. Additional research is needed to identify novel drugs by use of innovative high-throughput screening technologies and to improve experimental models to reflect human disease. Such advances will pave the way for lead candidates to be tested in thoroughly designed clinical trials in defined patient populations.

In a previous mBio article, Wadsworth and colleagues (mBio 9:e01419-18, 2018, https://doi.org/10.1128/mBio.01419-18) described Neisseria gonorrhoeae isolates that express low levels of azithromycin (Azi) resistance. Whole-genome sequencing and bioinformatic analysis suggested that the isolates had acquired DNA from commensal Neisseria spp. that caused numerous nucleotide changes in the mtr locus, which contains genes for a transcriptional repressor (MtrR) and three proteins (MtrC-MtrD-MtrE) that form a multidrug efflux pump known to export macrolides. Strong regions of linkage disequilibrium mapped to the overlapping mtrR and mtrCDE promoters and mtrD. Genetic analyses revealed that these mosaic-like sequences increased transcription of mtrCDE and MtrD function, respectively. These changes also had strong epistatic effects that collectively were responsible for decreased susceptibility to MtrCDE substrates, including Azi. The report emphasizes the importance of gene exchange among neisserial species and development of antibiotic resistance in gonococci, both of which have ramifications for detection of resistance markers and efficacy of antibiotic treatment regimens for gonorrhea.