Complicated Bacterial Infections Research Articles

Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline

Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear. Here, we present cryo-EM structures of tigecycline-bound human mitochondrial 55S, 39S, cytoplasmic 80S and yeast cytoplasmic 80S ribosomes. We find that at clinically relevant concentrations, tigecycline effectively targets human 55S mitoribosomes, potentially, by hindering A-site tRNA accommodation and by blocking the peptidyl transfer center. In contrast, tigecycline does not bind to human 80S ribosomes under physiological concentrations. However, at high tigecycline concentrations, in addition to blocking the A-site, both human and yeast 80S ribosomes bind tigecycline at another conserved binding site restricting the movement of the L1 stalk. In conclusion, the observed distinct binding properties of tigecycline may guide new pathways for drug design and therapy.

Complicated bacterial lung infections in patients with COPD

Patients with COPD are at increased risk of lung infections. Specific pathogens, including Pseudomonas aeruginosa, are associated with severe exacerbations requiring hospitalisation and death. New research summarised in this review highlights the importance of inhaled corticosteroids as a risk factor for lung infections. Reduction and discontinuation of treatment should be considered in patients with frequent or persistent infections. Long-term treatment with azithromycin and inhaled antibiotics may effectively reduce severe exacerbations in COPD.

Swarming Magnetic Fe3O4@Polydopamine-Tannic Acid Nanorobots: Integrating Antibiotic-Free Superficial Photothermal and Deep Chemical Strategies for Targeted Bacterial Elimination.

Micro/nanorobots (MNRs) are envisioned to provide revolutionary changes to therapies for infectious diseases as they can deliver various antibacterial agents or energies to many hard-to-reach infection sites. However, existing MNRs face substantial challenges in addressing complex infections that progress from superficial to deep tissues. Here, we develop swarming magnetic Fe3O4@polydopamine-tannic acid nanorobots (Fe3O4@PDA-TA NRs) capable of performing targeted bacteria elimination in complicated bacterial infections by integrating superficial photothermal and deep chemical strategies. The Fe3O4@PDA-TA nanoparticles (NPs), serving as building blocks of the nanorobots, are fabricated by insitu polymerization of dopamine followed by TA adhesion. When driven by alternating magnetic fields, Fe3O4@PDA-TA NPs can assemble into large energetic microswarms continuously flowing forward with tunable velocity. Thus, the swarming Fe3O4@PDA-TA NRs can be navigated to achieve rapid broad coverage of a targeted superficial area from a distance and rapidly eradicate bacteria residing there upon exposure to near-infrared (NIR) light due to their efficient photothermal conversion. Additionally, they can concentrate at deep infection sites by traversing through confined, narrow, and tortuous passages, exerting sustained antibacterial action through their surface TA-induced easy cell adhesion and subsequent membrane destruction. Therefore, the swarming Fe3O4@PDA-TA NRs show great potential for addressing complex superficial-to-deep infections. This study may inspire the development of future therapeutic microsystems for various diseases with multifunction synergies, task flexibility, and high efficiency.

Rapidly progressive interstitial lung disease combined with pneumocystis jiroveci pneumonia in a patient with single anti-TIF-1γ antibody positive dermatomyositis in the context of an underlying tumor

BackgroundInterstitial lung disease (ILD) is a frequently observed comorbidity in autoimmune diseases such as dermatomyositis/polymyositis (DM/PM), and it is significantly associated with specific autoantibody types. One unique antibody type is the anti-transcription intermediate factor-1γ antibody (anti-TIF-1γ Ab), which has a positive rate of only 7%. It is often found in combination with malignancy and rarely with ILD, particularly rapidly progressive ILD (RPILD). In some cases, the presence of ILD in individuals with DM may indicate a paraneoplastic syndrome. Pneumocystis jiroveci pneumonia (PJP) typically occurs due to intensive immunosuppressive therapy, human immunodeficiency virus (HIV) infection, or malignancy, and rarely as an isolated condition.Case presentationA 52-year-old man with a history of rapid weight loss but non-HIV infected and not immunosuppressed who presented with fever, cough, dyspnea, weakness of the extremities, characteristic rash and mechanic's hand. Pathogenic tests suggested PJP, laboratory tests suggested a single anti-TIF-1γ Ab positive DM, imaging suggested ILD, and pathology revealed no malignancy. RPILD and acute respiratory distress syndrome (ARDS) developed after anti-infection and steroid hormone therapy. After mechanical support therapy such as Extracorporeal Membrane Oxygenation (ECMO), the patient developed late-onset cytomegalovirus pneumonia (CMVP), complicated bacterial infection, and ultimately death. Additionally, we discuss the potential causes of rapid weight loss, the mechanisms by which anti-TIF-1γ Ab may lead to ILD, and the possible connection between anti-TIF-1γ Ab positivity, rapid weight loss, immune abnormalities, and opportunistic infections.ConclusionsThis case emphasizes the importance of early recognition of malignant tumors and pulmonary lesions, assessment of the body's immune status, prompt initiation of immunosuppressive treatment, and prevention of opportunistic infections in individuals with single anti-TIF-1γ Ab positive DM presenting with rapid weight loss.

High-level delafloxacin resistance through the combination of two different mechanisms in Staphylococcus aureus

Delafloxacin is a new fluoroquinolone indicated for the treatment of complicated bacterial skin infections caused by Staphylococcus aureus. Despite its recent approval by the US Food and Drug Administration, the emergence of S. aureus-resistant strains has been reported. As such, this study aimed to investigate the activity of delafloxacin against a collection of S. aureus, and to determine the mechanisms of resistance. The activity of delafloxacin was measured in 59 S. aureus clinical isolates [40 methicillin-resistant S. aureus (MRSA) and 19 methicillin-susceptible S. aureus (MSSA)]. Whole-genome sequencing (WGS) was performed in the isolates resistant to delafloxacin. The minimum inhibitory concentrations required to inactivate 50% and 90% of the isolates (MIC50 and MIC90, respectively) were higher in MRSA (0.19 mg/L and 0.75 mg/L, respectively) than in MSSA (0.008 mg/L and 0.25 mg/L, respectively). Furthermore, 10 S. aureus clinical isolates (16.9%) were categorized as resistant to delafloxacin. Regarding the WGS data, several mutations were found in the quinolone resistance-determining region. Nevertheless, a mutation in the same position (E84K and E84V) of topoisomerase IV (ParC) was found exclusively in the four high-level delafloxacin-resistant isolates. Interestingly, a plasmid-encoded qacC gene (efflux pump) was found to be harboured by the isolate with the highest delafloxacin MIC value (32 mg/L). The use of a wide-spectrum efflux pump inhibitor revealed an important contribution of this system to the acquisition of delafloxacin resistance. In conclusion, delafloxacin has activity against S. aureus, including MRSA. However, this study showed that mutations in position 84 of ParC and the acquisition of a QacC efflux pump are key factors for the development of delafloxacin resistance in S. aureus.

Recent advances of cell membrane-coated nanoparticles for therapy of bacterial infection.

The rapid evolution of antibiotic resistance and the complicated bacterial infection microenvironments are serious obstacles to traditional antibiotic therapy. Developing novel antibacterial agents or strategy to prevent the occurrence of antibiotic resistance and enhance antibacterial efficiency is of the utmost importance. Cell membrane-coated nanoparticles (CM-NPs) combine the characteristics of the naturally occurring membranes with those of the synthetic core materials. CM-NPs have shown considerable promise in neutralizing toxins, evading clearance by the immune system, targeting specific bacteria, delivering antibiotics, achieving responsive antibiotic released to the microenvironments, and eradicating biofilms. Additionally, CM-NPs can be utilized in conjunction with photodynamic, sonodynamic, and photothermal therapies. In this review, the process for preparing CM-NPs is briefly described. We focus on the functions and the recent advances in applications of several types of CM-NPs in bacterial infection, including CM-NPs derived from red blood cells, white blood cells, platelet, bacteria. CM-NPs derived from other cells, such as dendritic cells, genetically engineered cells, gastric epithelial cells and plant-derived extracellular vesicles are introduced as well. Finally, we place a novel perspective on CM-NPs' applications in bacterial infection, and list the challenges encountered in this field from the preparation and application standpoint. We believe that advances in this technology will reduce threats posed by bacteria resistance and save lives from infectious diseases in the future.

Ceftriaxone-Induced Gallbladder Stones in Children

Gallbladder stones in children is one complication that is mostly seen in diseases such as hemolytic diseases, liver disease, and obesity. It can also be a secondary complication of long-duration use of antibiotics like ceftriaxone. However, gallbladder stone, together with sludge themselves, is unusual within the children's population. We observed three children with gallbladder stones who were on along course of intravenous ceftriaxone. In this study, we present the three cases of children aged between eleven months to seven years who were treated with high doses and for an extended period (more than two weeks) of intravenous ceftriaxone for a complicated systemic bacterial infection. The goal of this study is to raise awareness about the possibility of developing gallbladder stones in pediatric patients who receive a long course of intravenous ceftriaxone.

Lipid-Polymer Hybrid Nanoparticles Enhance the Potency of Ampicillin against Enterococcus faecalis in a Protozoa Infection Model.

Enterococcus faecalis (E. faecalis) biofilms are implicated in endocarditis, urinary tract infections, and biliary tract infections. Coupled with E. faecalis internalization into host cells, this opportunistic pathogen poses great challenges to conventional antibiotic therapy. The inability of ampicillin (Amp) to eradicate bacteria hidden in biofilms and intracellular niches greatly reduces its efficacy against complicated E. faecalis infections. To enhance the potency of Amp against different forms of E. faecalis infections, Amp was loaded into Lipid-Polymer hybrid Nanoparticles (LPNs), a highly efficient nano delivery platform consisting of a unique combination of DOTAP lipid shell and PLGA polymeric core. The antibacterial activity of these nanoparticles (Amp-LPNs) was investigated in a protozoa infection model, achieving a much higher multiplicity of infection (MOI) compared with studies using animal phagocytes. A significant reduction of total E. faecalis was observed in all groups receiving 250 μg/mL Amp-LPNs compared with groups receiving the same concentration of free Amp during three different interventions, simulating acute and chronic infections and prophylaxis. In early intervention, no viable E. faecalis was observed after 3 h LPNs treatment whereas free Amp did not clear E. faecalis after 24 h treatment. Amp-LPNs also greatly enhanced the antibacterial activity of Amp at late intervention and boosted the survival rate of protozoa approaching 400%, where no viable protozoa were identified in the free Amp groups at the 40 h postinfection treatment time point. Prophylactic effectiveness with Amp-LPNs at a concentration of 250 μg/mL was exhibited in both bacteria elimination and protozoa survival toward subsequent infections. Using protozoa as a surrogate model for animal phagocytes to study high MOI infections, this study suggests that LPN-formulated antibiotics hold the potential to significantly improve the therapeutic outcome in highly complicated bacterial infections.

An overview of carbapenem, its resistance and therapeutic options for infections caused by carbapenem resistant bacteria

Carbapenems are beta-lactam drugs that have broadest spectrum of activity. They are commonly used as the drugs of last resort to treat complicated bacterial infections. They bind to penicillin binding proteins (PBPs) and inhibit cell wall synthesis in bacteria. Important members that are in clinical use include doripenem, ertapenem, imipenem, and meropenem. Unlike other members, imipenem is hydrolyzed significantly by renal dehydropeptidase; therefore, it is administered together with an inhibitor of renal dehydropeptidase, cilastatin. Carbapenems are usually administered intravenously due to their low oral bioavailability. Most common side effects of these drugs include nausea, vomiting, diarrhea, skin rashes, and reactions at the infusion sites. Increasing resistance to these antibiotics is being reported throughout the world and is posing a threat to public health. Primary mechanisms of carbapenem resistance include expulsion of drug and inactivation of the drug by production of carbapenemases which may not only hydrolyze carbapenem, but also cephalosporin, penicillin, and aztreonam. Resistance especially among Gram negative bacteria is of much concern since there are only limited therapeutic options available for infections caused by carbapenem resistant Gram-negative bacterial pathogens. Commonly used drugs to treat such infections include polymyxins, fosfomycin and tigecycline.

Light-Activatable Synergistic Therapy of Drug-Resistant Bacteria-Infected Cutaneous Chronic Wounds and Nonhealing Keratitis by Cupriferous Hollow Nanoshells.

Due to the inability to spontaneously heal and vulnerability to bacterial infection, diabetic patients are frustrated by unexpected epithelium injuries in daily life. Notably, a drug-resistant bacterial infection may result in a long-term impact to the natural function of damaged organs. It is imperative to develop strategies that promote injury recovery and eradicate drug-resistant infection simultaneously. Here, we present a composite structured cupriferous hollow nanoshell (AuAgCu2O NS) that consists of a hollow gold-silver (AuAg) core and Cu2O shell as a photothermal therapeutic agent for a cutaneous chronic wound and nonhealing keratitis with drug-resistant bacterial infection. The controllable photothermal therapeutic effect and released silver ion from the hollow AuAg core possess a synergistic effect to eradicate multi-drug-resistant bacteria, including extended-spectrum β-lactamase Escherichia coli (ESBL E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). Meanwhile, the released copper ion from the Cu2O shell could expedite endothelial cell angiogenesis and fibroblast cell migration, thus boosting wound-healing effects. In both infection-complicated disease models, the ophthalmic clinical score, wound closure rates, and histopathology analysis demonstrate that the AuAgCu2O NSs could facilitate the re-epithelialization at the wound area and eliminate the complicated bacterial infection from diabetic mice. A primary signal path involved in the promoted healing effect was further illustrated by comprehensive assays of immunohistochemical evaluation, Western blot, and quantitative polymerase chain reaction. Taken together, our AuAgCu2O NSs are shown to be potent candidates for clinical utilization in the treatment of diabetic epithelium injuries.

Bacteriological Profiles and Antibiotic Susceptibility Patterns in Complicated Bacterial Infections of the Ears, Nose and Throat

The objective of this study was to identify and map bacteriological profiles and antibiotic susceptibility patterns of complicated bacterial infections in the otorhinolaryngological (ENT) spectrum. Antibiotic resistance was another goal of our study. We defined complicated bacterial infections as: acute bacterial pathology of the ears, nose and throat with complications that required immediate surgical approach, chronic diseases of the ears, nose and throat that required surgical treatment due to ongoing bacterial infections, middle ear cholesteatoma with complications, complicated suppurated tonsillitis in children, intratonsillar abscess, parapharyngeal space abscess, cellulitis of the neck, face and/or involving cervical ganglia and neoplasms of the pharynx or larynx with an acute ongoing bacterial superinfection. The study was carried out over a period of 12 months, on a total number of 82 patients (children and adults), admitted in our department for the complicated bacterial diseases listed above. For the ENT spectrum, we uncovered that more than 50% of complicated bacterial infections were caused by 4 pathogens: Pseudomonas species, Staphylococcus aureus non-MRSA and MRSA species and Streptococcus species (other than Beta-haemolytic Group A Streptococci and Streptococcus pneumoniae). Almost two thirds of all complicated bacterial infections are complicated cases of sinusitis or mastoiditis that require immediate surgical treatment due to possible life-threatening complications. Keywords: complicated bacterial infection, bacteriological profiles, antibiotic resistance, bacterial culture, bacterial antibiotic susceptibility

Diagnostic pitfalls in pulmonary malformative pathology in children

Bronchogenic cyst in children is a lung malformative pathology that can often be confused with the initial presentation of infectious or tumor processes. The symp­toms may be minimal when bronchogenic cysts are found accidentally, or mimicking complicated bacterial lung infections. Imaging (lung CT or MRI) describes the lesion, and the surgical resection is postponed until the cyst becomes symptomatic or, frequently, overinfected. The authors present two recent cases of children diagnosed with bronchogenic cyst – at the age of small infant, and at 5 years old, with their peculiarities of presentation and evolution.

Synthesis of silver nanoparticles using oxidized amylose and combination with curcumin for enhanced antibacterial activity

Many kinds of multi-drug-resistant microorganisms have appeared. Moreover, monotherapy is increasingly no longer adequate for many complicated bacterial infections. Therefore, development of efficient combination antibacterial agent is becoming crucial. Herein, we present a hybrid antibacterial agent with enhanced antibacterial activity and high aqueous dissolubility based on silver nanoparticles and curcumin. The silver nanoparticles were firstly synthesized using oxidized amylose as an environmentally friendly reducing agent and stabilizer. Then, curcumin was added into the above mixture to get the hybrid antibacterial agent. The hybrid antibacterial agent presented high dissolubility in aqueous solution and enhanced antibacterial activity. In addition, the hybrid antibacterial agent presented good antioxidant activity and cell compatibility. Overall, the developed hybrid antibacterial agent has a potential to combat multiple bacteria-induced infections of wound surfaces.

The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Francisella tularensis SCHU S4 Infection in BALB/c Mice and Cynomolgus Macaques.

TP-271 is a novel, fully synthetic fluorocycline in development for complicated bacterial respiratory infections. TP-271 was active in vitro against a panel of 29 Francisella tularensis isolates, showing MICs against 50% and 90% of isolates of 0.25 and 0.5 μg/ml, respectively. In a mouse model of inhalational tularemia, animals were exposed by aerosol to 91 to 283 50% lethal doses (LD50)/mouse of F. tularensis SCHU S4. Following 21 days of once-daily intraperitoneal dosing with TP-271 at 3, 6, 12, and 18 mg/kg of body weight/day, initiating at 24 h postchallenge, survival was 80%, 100%, 100%, and 100%, respectively. When treatment was initiated at 72 h postchallenge, survival was 89%, 100%, 100%, and 100% in the 3-, 6-, 12-, and 18-mg/kg/day TP-271 groups, respectively. No mice treated with the vehicle control survived. Surviving mice treated with TP-271 showed little to no relapse during 14 days posttreatment. In a nonhuman primate model of inhalational tularemia, cynomolgus macaques received an average aerosol exposure of 1,144 CFU of F. tularensis SCHU S4. Once-daily intravenous infusion with 1 or 3 mg/kg TP-271, or vehicle control, for 21 days was initiated within 6 h of confirmed fever. All animals treated with TP-271 survived to the end of the study, with no relapse during 14 days after the last treatment, whereas no vehicle control-treated animals survived. The protection and low relapse afforded by TP-271 treatment in these studies support continued investigation of TP-271 for use in the event of aerosolized exposure to F. tularensis.

Susceptibility to Urinary Tract Infection: Benefits and Hazards of the Antibacterial Host Response.

A paradigm shift is needed to improve and personalize the diagnosis of infectious disease and to select appropriate therapies. For many years, only the most severe and complicated bacterial infections received more detailed diagnostic and therapeutic attention as the efficiency of antibiotic therapy has guaranteed efficient treatment of patients suffering from the most common infections. Indeed, treatability almost became a rationale not to analyze bacterial and host parameters in these larger patient groups. Due to the rapid spread of antibiotic resistance, common infections like respiratory tract- or urinary-tract infections (UTIs) now pose new and significant therapeutic challenges. It is fortunate and timely that infectious disease research can offer such a wealth of new molecular information that is ready to use for the identification of susceptible patients and design of new suitable therapies. Paradoxically, the threat of antibiotic resistance may become a window of opportunity, by encouraging the implementation of new diagnostic and therapeutic approaches. The frequency of antibiotic resistance is rising rapidly in uropathogenic organisms and the molecular and genetic understanding of UTI susceptibility is quite advanced. More bold translation of the new molecular diagnostic and therapeutic tools would not just be possible but of great potential benefit in this patient group. This chapter reviews the molecular basis for susceptibility to UTI, including recent advances in genetics, and discusses the consequences for diagnosis and therapy. By dissecting the increasingly well-defined molecular interactions between bacteria and host and the molecular features of excessive bacterial virulence or host-response malfunction, it is becoming possible to isolate the defensive from the damaging aspects of the host response. Distinguishing "good" from "bad" inflammation has been a long-term quest of biomedical science and in UTI, patients need the "good" aspects of the inflammatory response to resist infection while avoiding the "bad" aspects, causing chronicity and tissue damage.

Complementary and alternative medicine for respiratory tract infectious diseases: prevention and treatments.

Respiratory tract infectious diseases are a group of the most common, widespread diseases, from common cold and influenza to tuberculosis and pneumonia; some of them may cause serious and even life-threatening health problems. Most cases of upper respiratory tract infectious diseases include common cold and influenza, which are mainly caused by various virus infections, and tuberculosis, pneumonia, and other low respiratory tract infectious diseases caused by different bacterial infections. Releasing the symptoms and preventing complicated bacterial infection are a rule of treating virus infected upper respiratory tract infectious diseases. Traditionally, herbal medicines are used to treat and prevent the respiratory tract infectious diseases such as common cold and influenza worldwide. For example, more than two hundred patent products of traditional Chinese medicines have been approved into market for treatment and prevention of the common cold as well as influenza. In the past decades, some herbal medicines are developed as injections for clinical use for treating respiratory tract infections, such as Caihu injection, Shuanghuanglian injection, Yuxincao injection, and Qinkailing injection. Some of these medicines are believed to effectively release the symptoms; some are believed to strengthen the immune function of patient and therefore result in the virus and bacteria being eliminated; some are believed to kill the microorganisms directly. A fact is that although a lot of herbal medicines are widely used clinically, most evidence supporting their use came from poorly reported published clinical studies or studies with questionable methodology, as Drs. Q. Yang, H. Zhang, C. Zou, and L. Wu, concluded in their systematic reviews. Call for high quality evidence is a mission of this special issue. Fortunately, Dr. J. Chang and her colleagues contributed high quality evidence about a patent Chinese medicine Shi-Cha capsule for common cold by a well-designed, well-conducted, and well-reported randomized controlled trial. In this multicenter study, they have done very well on the ethicas issues including protocol aproval by ethical committee, properly informed consent and registered their protocol in a public clinical trial registry—Chinese Clinical Trial Registry; and high quality methodological issues, including the randomization method and allocation procedure, the recruitment of patients, the data management, the analysis method of results, all of these were described in detail and very clearly according to CONSORT statement. This transparency makes readers confident to trust the result of the study and we believe such evidence should be graded as high quality. if the reporting referes to CONSORT for TCM to provide more information of the principle of using Shi-Cha capsule for with “wind-cold type common cold” will makes readers better understanding on the rational of this medicine. Another advantage of this trial is that placebo control was used for comparison with Shi-Cha capsule. Usually, use of a medicine in which “the effect is accepted by public recognition” as the control is one of rules of the new medicine development clinical trial in China. The shortcoming of this rule is that it caused difficulty to assess the effects for a lot of traditional Chinese medicines because of the lack of evidence of effect of the controls. For the self-limited disease, a placebo control should be encouraged to be used in the treatment study. We believe that this study and its report could be a good example of high quality study and good reporting. Another valuable thing we have seen is that Dr. C. Zou and his colleagues, physicians of traditional Chinese medicine, are using evidence-based medicine (EBM) method to critically appraise the evidence and using the results to guide their clinical practice successfully. This absolutely is a revolutionary event in the field while most traditional medical clinicians may not know EBM exactly. We hope more and more clinicians in the field can use EBM method to guide their practices and make the health care service better and better. Studies came from France, Japan, South Africa, and Taiwan provide from in vitro and animal study suggesting that some herbal medicines may have antimicrobial activity or can strengthen the immune function. It is expected that these lines of evidence will result in more confidence to support the clinical use of complementary and alternative medicines. Taixiang Wu Zhao-Xiang Bian Minawaer Abudu Denise Adams Seong-Gyu Ko

Clinical Analysis of Influenza A (H1N1) Viral Pneumonia Complicated with Bacterial Infection

Purpose: We investigated the efficacy of potent or combined antibiotics in patients suffering bacterial infections secondary to H1N1 by retrospectively analyzing their bacterial pathogen spectrum and clinical characteristics. Methods: Multi-center retrospective analysis was performed using clinical data of H1N1 patients from 27 hospitals in Hebei Province, China, from November 1 to December 31, 2009. Results: Of 480 H1N1-infected patients enrolled from an inpatient clinic, 91 were positive for bacterial culture. Bacteria were detected in sputum culture at 7.00 ± 8.87 days post-admission. Compared with the negative group, the patients in the positive sputum culture group had a higher mean age and prevalence of basic diseases, higher APECHEII (Acute Physiology and Chronic Health Evaluation II) score within 24 hours of admission, longer hospital stays, and higher mortality. In total, 189 bacterial strains were isolated, with the majority of samples testing positive for Acinetobacter baumanii (47), Streptococcus viridians (26), or Pseudomonas aeruginosa (19). S. viridians was the major cause of infection within 3 days of admission, while A. baumanii infection was more prevalent from 4 days post-admission; there was a significant difference in the constituent ratio between the two pathogens (p 0.001). Compared with patients administered common antibiotics, the potent antibiotics group showed no significant difference in hospitalization time, time until bacterial detection, mortality, or detection ratio of resistant strains (p > 0.05). Conclusions: Complicated bacterial infection in H1N1 patients increases hospitalization time and mortality. Gram-negative bacilli and multi-resistant strains are the main sources of infection. Early administration of potent or combined antibiotics, even during the period of rapid onset, may not be suitable in H1N1-infected patients, particularly previously healthy young patients.

Comparison of micafungin and voriconazole in the treatment of invasive fungal infections in kidney transplant recipients

Invasive fungal infections are a major threat to renal transplant recipients. Micafungin and voriconazole are two useful antifungal agents for treating such infections. Our objective is to evaluate the comparative efficacy and safety of micafungin and voriconazole in the initial treatment of such infections. In this prospective, multicentre, open-labelled, randomized, controlled trial, renal transplant recipients with invasive fungal infections were assigned to receive either micafungin or voriconazole. The enrolled subjects received a kidney transplant between March 2008 and March 2010 at one of the two transplant centres in Henan Province, China. The efficacy and adverse effects of the two treatments were compared. The clinical trial enrolled 65 patients, of whom 31 were treated with micafungin, and 34 with voriconazole. The rates of microbiological evidence of infection in the micafungin and voriconazole groups were 64.5% and 70.5%, respectively, whereas the rates of Candida as the major cultured fungus were 80.0% and 75.0%, respectively. Complicated bacterial infection rates in the two treatment groups were 38.7% and 32.4%, respectively, whereas complicated CMV viral infection occurred at a rate of 19.2% and 23.5%, respectively. Fungal infection within one to 3 months after transplant was 83.6% (26/31) and 85.3% (29/34) in the micafungin and voriconazole groups, respectively. There was no significant difference between the two groups in terms of efficacy, survival beyond 10 days and discontinuation of treatment because of lack of efficacy (P > 0.05). Mortality rates in the micafungin and voriconazole groups were 9.7% (3/31) and 12.1% (4/33), respectively. Rates of adverse effects in the two groups were 41.9% and 51.6% (P > 0.05), respectively. This is the first comparison of micafungin and voriconazole in renal transplant patients. Our study shows that the effectiveness of micafungin was similar to that of voriconazole in such patients.

Minocycline Hydrochloride: The Emerging Evidence of Its Therapeutic Value in Complicated Bacterial Infections

In order to address increasing antimicrobial resistance issues in combination with few new antimicrobial agents, minocycline has renewed interest for new uses in resistant, serious infections. Minocycline is a broad-spectrum antimicrobial with activity against Gram-positive and -negative bacteria, including aerobes and anaerobes as well as Mycoplasma, Chlamydia, Rickettsia, Nocardia, Legionella, and various spirochetes. Minocycline has many favorable attributes including good pharmacokinetic profile, high tissue penetration, intravenous and oral preparation, and negligible dose adjustments for patients with renal and hepatic dysfunction. In case studies, minocycline does display efficacy in the treatment of S. aureus skin and soft tissue infections, and has been used successfully in the management of patients with S. aureus endocarditis, including MRSA. Minocycline-rifampin impregnated catheters are efficacious in both preventing colonization of catheters as well as preventing bloodstream infections associated with catheter use. In Gram-negative infections, case reports have described the successful use of minocycline for pneumonia, hospital-associated and ventilator-associated type, and wound infections due to A. baumanii and S. maltophilia. In sexually transmitted infections, minocycline may be an attractive alternative to doxycycline in the treatment of nongonococcal urethritis and mucopurulent cervicitis. It has demonstrated efficacy in the treatment of neurosyphilis in those patients with penicillin allergies. As bacterial resistance issues continue to worsen, additional clinical evidence for the use of minocycline in complicated bacterial infections may arise, further integrating its place in therapy for these infections. Most of this evidence will likely come from case report, cohort, or observational studies since prospective randomized trials with minocycline will be difficult to perform.

Mechanisms of quinolone resistance and implications for human and animal health

Quinolone antibiotics have been widely used in human and veterinary medicine. This has caused the development of resistance and difficulties in the treatment of complicated bacterial infections in humans. The resistance to quinolones develops due to chromosome mutations and it can also be transferred by plasmids. The target enzyme for quinolones in Gram-negative bacteria is Gyrasa A, while the target enzyme in Grampositive bacteria is mostly topoisomerase IV. Gyrase A consists of two subunits encoded by genes gyrA and gyrB. The function of the enzyme is to introduce negative super coiling in DNA and therefore is essential for the replication of bacteria. Quinolone resistance develops if point mutations at 83 and/or 87 codon are introduced on gyrA. Establishing a minimal inhibitory concentration (MIC) to this group of antimicrobials will reveal possible mutations. Recently it was discovered that quinolone resistance is transmittable by plasmid termed PMQR (plasmid mediated quinolone resistance). The target gene marked qnr encodes a pentapeptide repeat family protein. Pentapeptide repeats form sheets, involved in protein-protein interactions. Qnr protein binds to GyrA protecting the enzyme from the inhibitory effect of ciprofloxacin. The distribution of qnr related resistance is higher in humans than in animals. In poultry, however, this type of resistance is present more than in other animals. Plasmid mediated resistance contributes to the faster spread of quinolone resistance. Proper food handling will significantly contribute to decreasing the risk from infection to which people are exposed. In medical and veterinary laboratories antimicrobial resistance monitoring in clinical and environmental isolates is advised. Since correlation between antibiotics application and antimicrobial resistance is often suggested, antimicrobial use must be under strict control of the authorities both in human and in veterinary medicine. .