Clinical outcomes after faecal microbiota transplant by retention enema in both immunocompetent and immunocompromised patients with recurrent Clostridioides difficile infections at an academic medical centre.

BACKGROUND: Recurrent Clostridioides difficile infection (CDI) is one of the most common and challenging infections to treat in healthcare facilities. Faecal microbiota transplantation (FMT) is recommended as a definitive treatment option. METHODS: We performed a retrospective review of 50 patients from January 2015 to December 2019 who underwent FMT for recurrent CDI. Primary outcome was recurrence of CDI within 12-weeks of FMT and secondary outcomes were the need for repeat FMT, serious adverse outcomes related to FMT and all-cause mortality. RESULTS: Fifty charts were reviewed, of which 47 cases comprising 17 immunocompromised patients treated with FMT via retention enema were included in the study. The majority of the patients had ≥3 recurrent CDIs (62%). Nine (19%) patients failed to respond to the first FMT and five underwent repeat FMT within four to 12 weeks. The cure rate was 81% after the first FMT (38/47) and 91% after the second FMT treatment (43/47). Serious adverse events occurred in 2% and all-cause mortality was 2% at 90-day follow up. CONCLUSION: Our study demonstrated the safety and efficacy of FMT administered via retention enema, a simple bedside procedure, for the treatment and prevention of recurrent non-severe and severe CDI with an overall cure rate of 91%.

Geographically-based evaluation of multidrug resistance trends among Streptococcus pneumoniae in the USA: findings of the FAST surveillance initiative (2003-2004).

Surveillance initiatives to track Streptococcus pneumoniae resistance trends are important for understanding the current in vitro effectiveness of available antimicrobial agents. The antimicrobial susceptibility profiles of S. pneumoniae (n=1479 isolates) collected from 17 geographical areas across the USA (2003-2004) were analysed; 36.8% of isolates were resistant to one or more agents (24.4% were multidrug-resistant, i.e. resistant to two or more antimicrobial classes). Multidrug resistance involved resistance to beta-lactams, macrolides, tetracycline and trimethoprim/sulphamethoxazole, but rarely fluoroquinolones (>96% of multidrug-resistant isolates were fluoroquinolone-susceptible). Multidrug resistance rates were prominent regardless of the geographical region surveyed. As this trend continues, the empirical therapeutic options for S. pneumoniae infections will diminish and there will be an ongoing need to evaluate the effectiveness of potent fluoroquinolones such as gemifloxacin.

Adverse cutaneous reactions and drugs: a focus on antimicrobials.

Rashes are a common adverse event observed during antimicrobial therapy. Many rashes are mild to moderate in intensity, however some reactions can be the prelude to much more severe outcomes such as Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necolysis. Several risk or influencing factors are known such as female gender, age and concomitant viral infections, and these may apply to more than one drug class. The incidence of rashes and other cutaneous reactions vary, however rates of >3% are reported with the beta-lactams while serious reactions such as SJS are observed with trimethoprim-sulphamethoxazole. Newer fluoroquinolone agents are devoid of the moiety which caused phototoxic reactions, while rates of rash vary from < 1%-3% or higher if longer courses of therapy are given. Serious systemic events have not been reported with these agents unlike other older, well-accepted antimicrobials. Rashes, while occasionally itchy and sometimes transiently unsightly, have less of an impact on a patient's daily activities than diarrhea, nausea or other more profound adverse events. However, it is essential that any rash be carefully monitored for possible, but rare, serious systemic events ensuing.

Geminofloxacin for the management of community-acquired respiratory tract infections.

Community-acquired lower respiratory tract infections (LRTIs) exert a growing clinical and financial burden on healthcare systems and employers. In addition, antimicrobial resistance among pathogens, such as Streptococcus pneumoniae, has compromised the use of commonly prescribed antimicrobial compounds. Newer fluoroquinolones have been developed to meet these emerging demands. Gemifloxacin is a potent, dual-acting fluoroquinolone with excellent activity against S. pneumoniae (MIC(90)0.03-0.06 microg/ml) including those strains demonstrating resistance to other classes of antibiotics. Gemifloxacin demonstrated excellent clinical success in community-acquired lower respiratory infections, has an acceptable safety profile, and is a cost-effective alternative in the management of LRTIs including those caused by resistant pathogens.

Future trends in antimicrobial chemotherapy: expert opinion on the 43rd ICAAC.

The current document bestows an expert synopsis of key new information presented at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in 2003. Data is presented on the socio-political aspects of and policies on antimicrobial prescribing, novel mechanisms of resistance in Streptococcus pneumoniae, and current epidemiological trends in global resistance. Novel information on new (and existing) antimicrobial agents--new penicillins, cephalosporins, monobactams and oxipenem inhibitors, ketolides, glycopeptides, fluoroquinolones (and hybrids), peptides, daptomycin, aminomethylcyclines, glycylcyclines, and newer formulations of agents such as amoxycillin-clavulanate--provides renewed hope that resistant pathogens can be controlled through use of more potent agents. Improved strategies for the use of existing antimicrobial agents, such as the use of high-dose regimens, short-course therapy, also may delay or reduce the development of resistance and preserve the value of our antibiotic armamentarium.

Antimicrobial selection for community-acquired lower respiratory tract infections in the 21st century: a review of gemifloxacin.

Community-acquired lower respiratory tract infections (LRTIs) are more prevalent in the elderly than in children and younger adults and form a significant proportion of all consultations and hospital admissions in this older age group. Furthermore, in a world of increasing life expectancy the trend seems unlikely to be reversed. Antimicrobial treatment of community-acquired pneumonia (CAP) must cover Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, and in many circumstances should also cover the intracellular (atypical) pathogens. In contrast, acute exacerbations of chronic bronchitis (AECB) are mainly associated with H. influenzae and S. pneumoniae and not with atypical bacteria: in severe cases, other Gram-negative bacteria may be involved. Frequently in LRTIs, the aetiology of the infection cannot be identified from the laboratory specimens and treatment has to be empirical. In such situations it is important to not only to use an antibiotic that covers all likely organisms, but also one that has good activity against these organisms given the local resistance patterns. Gemifloxacin is a new quinolone antibiotic that targets pneumococcal DNA gyrase and topoisomerase IV and is highly active against S. pneumoniae including penicillin-, macrolide- and many ciprofloxacin-resistant strains, as well as H. influenzae and the atypical pathogens. In clinical trials in CAP and AECB, gemifloxacin has been shown to be as effective a range of comparators and demonstrated an adverse event profile that was in line with the comparator agents. In one long-term study in AECB significantly more patients receiving gemifloxacin than clarithromycin remained free of recurrence after 26 weeks. The improved potency, broad spectrum of activity and proven clinical and bacteriological efficacy and safety profile should make it a useful agent in the 21st century battle against community-acquired LRTIs.

A new respiratory fluoroquinolone, oral gemifloxacin: a safety profile in context.

Gemifloxacin is a broad-spectrum quinolone antibacterial with enhanced potency against Gram-positive bacteria, including multi-drug resistant Streptococcus pneumoniae, and retained potency against Gram-negative bacilli and bacterial strains resistant to other antibiotics. It has proven particularly effective in respiratory and urinary tract infection. This review presents safety data from 6775 patients included in clinical trials, receiving either the recommended 320 mg once daily oral dose of gemifloxacin, or standard dose of other quinolones, macrolides or beta-lactams (n = 5248). Studies in healthy volunteer and special populations are also reported. Adverse experiences (AEs) were observed in 44.7% of gemifloxacin-treated patients and 47.5% of those who received comparator drugs. Mild gastro-intestinal adverse drug reactions (ADRs) (diarrhoea 5.1%, nausea 3.9%) predominated. Rash, usually maculo-papular and in no case proceeding to more severe eruptions, was observed in 3.6% of those receiving gemifloxacin. A higher incidence of rash (>20%) was observed in young women and was the subject of further study. Adverse drug reactions suspected or probably related to treatment occurred in 17.4% of patients receiving gemifloxacin and in 20% of those receiving comparator antibiotics. Diarrhoea and nausea were experienced by 3.6 and 2.7%, respectively, of gemifloxacin-treated patients (4.6 and 3.2% of comparators), rash by 2.8% (0.6% of comparators) and headache by 1.2% (1.5% of comparators). Gemifloxacin-related vomiting (0.9%), dizziness (0.8%) and taste perversion (0.3%) were uncommon. Treatment discontinuation followed one or more adverse drug reactions in 2.2% of gemifloxacin-treated patients (0.9% due to rash) and 2.1% of comparator-treated patients. A total of 63 deaths (33 receiving gemifloxacin) occurred in the trial population: none were considered related to treatment. A slight prolongation in QT interval (2.56 ms (S.D. +/-24.5)) was observed in gemifloxacin-treated patients: no cardiac arrhythmias were reported. There was a low incidence of liver function tests (LFTs) classified as of potential clinical concern: gemifloxacin (0.4-1.2%), comparators (0.2-1.3%). Serious adverse events (SAEs), occurring during but not necessarily related to therapy, occurred in 3.6% of gemifloxacin-treated patients (4.3% of comparators). SAEs related to treatment agents were rare (0.4% in each group) and included rash (0.1%) and elevated liver enzymes (<0.1%). Gemifloxacin was well tolerated by the elderly, those with renal or hepatic impairment and when co-administered with omeprazole, digoxin, theophylline, warfarin (with which there were no significant interactions) and Maalox. In conclusion, gemifloxacin 320 mg once daily demonstrated a favourable safety and tolerability profile similar to that of comparator antibiotics, including other quinolones.

Haemophilus parainfluenzae infection of respiratory mucosa.

The pathogenicity of Haemophilus parainfluenzae (Hpi) in the respiratory tract is unclear, in contrast to the accepted pathogenicity of its close relative non-typable H. influenzae. We have investigated the interaction of two Hpi isolates with the mucosa of adenoid and bronchial tissue organ cultures. The adherence of bacteria to the mucosa of organ cultures, the effect of broth culture filtrates on human nasal epithelium, and interleukin (IL)-8 production by A549 cell cultures was investigated. Hpi 4846 adhered infrequently in clusters of pleomorphic cocco-bacilli to areas of epithelial damage, mucus and unciliated cells in adenoid organ culture experiments at 24 h, but not bronchial mucosa. Hpi 3698 was seen in only one adenoid and no bronchial organ cultures at 24 h. In separate experiments, Hpi 3698 was cleared more rapidly from the centre of the adenoid organ culture and was not cultured at 24 h. Although not adhering to the mucosa at 24 h, Hpi 3698, but not Hpi 4846, caused an increase in the amount of epithelial damage in both types of organ culture. Broth culture filtrates of both strains caused immediate slowing of ciliary beat frequency that progressed, and disrupted epithelial integrity. Dialysed culture filtrates of both strains stimulated IL-8 production by A549 cells, with the culture filtrate of Hpi 3698 being most potent. We conclude that two strains of Hpi varied in their adherence to adenoid tissue, and neither adhered to bronchial tissue. These results lead us to speculate that Hpi is only likely to be a pathogen in the lower respiratory tract when impaired airway defences delay bacterial clearance.

Safety of fluoroquinolones: An update.

The fluoroquinolone class of antimicrobials has been in clinical use for over 13 years. During that period, some representatives of the class have been extensively prescribed, such as ciprofloxacin and levofloxacin, while others have seen minimal use and have been restricted or withdrawn, namely, trovafloxacin and grepafloxacin. Manipulation of the fluoroquinolone structure by substituting a range of moieties around the core has yielded enhanced antibacterial activity, but in some cases this has come at a price. Specific substitutions are discussed in relation to particular recognized adverse events. In the present paper, newly introduced fluoroquinolones, such as moxifloxacin and gatifloxacin, are examined in terms of anticipated class effects and recent clinical experience. These antimicrobials are associated with reactions such as diarrhea, nausea, headache and other typical antimicrobial phenomena at rates less than 5%. New fluoroquinolone agents should be examined carefully in light of structural findings until adequate clinical data are amassed.

The efficacy of moxifloxacin in acute exacerbations of chronic bronchitis: a Spanish physician and patient experience.

Chronic bronchitis is a debilitating disease affecting many millions of patients globally. They suffer multiple acute exacerbations each year, often requiring many courses of antimicrobials to enable them to return to normal. The impact of the condition on both the individual patient and society as a whole is considerable and growing; thus antimicrobial therapy should induce rapid and effective outcomes as soon as possible. This open, community-based study of 5737 patients enrolled by over 2000 primary care physicians from across Spain examined the clinical effect of oral moxifloxacin on patients' signs and symptoms of acute exacerbations of chronic bronchitis (AECB) over a 45-day period. The symptoms were assessed using daily diary cards in addition to physician evaluations. Clinical assessment at day 7 showed 93.0% of patients were cured. The patient diary card showed that two-thirds of patients felt better by day 3 or 4. Adverse events were reported in 3.5% of patients in this study, the most common being diarrhoea, nausea and dizziness, and epigastric pain. These reactions were mild to moderate in intensity. There were no patient deaths due to infection during the study. Physicians and patients reported that once-daily moxifloxacin gave fast relief of symptoms of acute exacerbations of chronic bronchitis.

Antimicrobial resistance mechanisms: what's hot and what's not in respiratory pathogens.

Community respiratory tract pathogens comprise Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and a few other select, but less frequent, species such as atypical bacteria, staphylococci, and some gram-negative organisms. In addition to an array of virulence factors, these bacteria have also developed a propensity to withstand a range of antimicrobial agents. These resistance mechanisms occur as either target site or antibiotic modifications or antibiotic transportation changes (prevention of cell entry or agent efflux). The genetic coding for these changes can be transmitted to progeny every 20 minutes or can be acquired from the normal flora via transformation. Presently, it is this acquisition of naked DNA by pneumococci that is a "hot" topic and the realization that unless antimicrobials are used more thoughtfully, then new agents can be rapidly rendered redundant. Other potential, but as yet unfounded, resistance scenarios include the acquisition of extended spectrum beta-lactamases by H. influenzae and the development of ribosomal changes to obviate the ketolides and oxazolidinones. To prevent the continued escalation of antimicrobial resistance, new approaches to antimicrobials must be implemented soon.

Clinical experience in Germany of treating community-acquired respiratory infections with the new 8-methoxyfluoroquinolone, moxifloxacin.

Moxifloxacin, a new 8-methoxyfluoroquinolone, was evaluated in a large community-based study involving 16,007 patients over a 9-month period. This study was designed as a large post-marketing observational study of the speed, efficacy and tolerability of moxifloxacin when used in clinical practice for the treatment of community-acquired bacterial pneumonia, or acute exacerbations of chronic bronchitis. Physicians and patients were specifically questioned about overall efficacy and safety as well as symptom relief. According to physicians' assessments 96.3% of patients were cured or improved after moxifloxacin treatment. Symptom relief ('feeling better') occurred in almost 70% of patients by day 3 and only 2.3% reported an adverse drug reaction. No individual adverse drug reaction was reported at a frequency above 1%. Among the 209 events considered as serious, only 34 were regarded as possibly or probably related to therapy. There were no moxifloxacin-related clinically relevant cases of phototoxicity, hepatotoxicity or cardiotoxicity. Overall, 92.1% of patients considered moxifloxacin to have been beneficial.

Treatment outcomes in acute exacerbations of chronic bronchitis: comparison of macrolides and moxifloxacin from the patient perspective.

Moxifloxacin, a new respiratory quinolone, was compared with the macrolides azithromycin, clarithromycin and roxithromycin in a cohort study to assess clinical, safety and health-related outcomes of these antimicrobials in general practice settings. In total 332 patients with acute exacerbations of chronic bronchitis (AECB) each received one of the antimicrobial agents for a standard short course of therapy. Random allocation of therapeutic agents occurred by centre, not individuals, and the drugs were prescribed in an open manner. In addition to clinical evaluation by their physicians, all patients kept daily diaries to assess AECB symptoms over the study period, therapy received and quality of life. The overall clinical response rate was 96% and all four regimens were well tolerated. After 14 days there were no significant differences between the study groups, but analyses of patients' daily evaluations of certain AECB specific symptoms showed a faster response rate in the moxifloxacin group.