The role of antibiotics in the prevention of cross infections in newborn infants and mothers during the puerperium]

Epidemiological efficiency of antibiotic prophylaxis of hospital infections (HIs) in maternity homes was analyzed by the materials on the clinical observation of 43995 newborns and their mothers within a period of 1986 to 1989 as well as by the data on the bacteriological examination of 6616 smears from the mucosa of the nose, pharynx, rectum and umbilical wounds of 1890 newborns carried out within the same period. It was shown that the prophylactic use of the antibiotics in the maternity homes led to changes in the microflora colonizing the newborns. The more massive was the use of the antibiotics in the departments of newborns and the postnatal departments, the more intensive was replacement of gram-positive microflora in the newborns by gram-negative organisms among which Klebsiella strains with high antibiotic resistance predominated. This involved an increase in the incidence of pneumonia and sepsis in the newborns and a higher death rate among the newborns due to HIs. In parallel there was observed an increase in the incidence of metro-endometritis in the puerperae++ and a simultaneous decrease in the number of the cases with lactational mastitis as a result of lower numbers of Staphylococcus aureus cultures isolated from various loci of the newborns. It was concluded that antibiotics were not the drugs to be used as prophylactic agents in control of HIs in maternity homes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Subtractive Proteomics and Immuno-informatics Approaches for Multi-peptide Vaccine Prediction Against Klebsiella oxytoca and Validation Through In Silico Expression

International Journal of Peptide Research and Therapeutics - Klebsiella oxytoca is a gram-negative bacterium. It is opportunistic in nature and causes hospital acquired infections....     

Chemotherapy for Bacterial Infections of the Central Nervous System

Over the past six years, many new agents have become available for the treatment of bacterial central nervous system (CNS) infections. Certain principles guide the use of these agents for CNS infections: first, an antimicrobial agent must be able to penetrate the CNS to be effective; second, the CNS is a “relatively immunoincompetent site” so that an antimicrobial must achieve levels within the CNS capable of killing the offending bacterium. The lack of efficacy of chloramphenicol for meningitis due to gram-negative aerobes is probably due to its failure to achieve such killing levels, whereas the success of the newer cephalosporins, such as cefotaxime and ceftriaxone, is due to their very high killing activity against these organisms. Penicillin remains the first choice for pneumococcal and meningococcal meningitis. Ampicillin plus chloramphenicol is still recommended as initial therapy for meningitis due to Hemophilus influenzae. The newer cephalosporins are now the first choice for the treatment of meningitis due to many gram-negative bacilli. Trimethoprim-sulfamethoxazole may also be useful in some of these infections and those due to Listeria monocytogenes. In the treatment of severe CNS infections, a team approach is advised to ensure optimal therapy.     

Role of type 1 and type 3 fimbriae in <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> biofilm formation

Background  

Klebsiella pneumoniae is an important gram-negative opportunistic pathogen causing primarily urinary tract infections, respiratory infections, and bacteraemia. The ability of bacteria to form biofilms on medical devices, e.g. catheters, has a major role in development of many nosocomial infections. Most clinical K. pneumoniae isolates express two types of fimbrial adhesins, type 1 fimbriae and type 3 fimbriae. In this study, we characterized the role of type 1 and type 3 fimbriae in K. pneumoniae biofilm formation.     

Effectiveness of using aminoglycoside antibiotics in septicemia and urinary tract infections in newborn infants

Data on the etiological structure of sepsis and urinary infections in newborns are presented. The leading role of gram-negative microflora is shown. Analysis of the antibioticograms revealed that netilmicin, amikacin and nipocin had the highest activity.     

Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention

Multidrug-resistant bacteria are the cause of an increasing number of deadly pulmonary infections. Because there is currently a paucity of novel antibiotics, phage therapy--the use of specific viruses that infect bacteria--is now more frequently being considered as a potential treatment for bacterial infections. Using a mouse lung-infection model caused by a multidrug resistant Pseudomonas aeruginosa mucoid strain isolated from a cystic fibrosis patient, we evaluated bacteriophage treatments. New bacteriophages were isolated from environmental samples and characterized. Bacteria and bacteriophages were applied intranasally to the immunocompetent mice. Survival was monitored and bronchoalveolar fluids were analysed. Quantification of bacteria, bacteriophages, pro-inflammatory and cytotoxicity markers, as well as histology and immunohistochemistry analyses were performed. A curative treatment (one single dose) administrated 2 h after the onset of the infection allowed over 95% survival. A four-day preventive treatment (one single dose) resulted in a 100% survival. All of the parameters measured correlated with the efficacy of both curative and preventive bacteriophage treatments. We also showed that in vitro optimization of a bacteriophage towards a clinical strain improved both its efficacy on in vivo treatments and its host range on a panel of 20 P. aeruginosa cystic fibrosis strains. This work provides an incentive to develop clinical studies on pulmonary bacteriophage therapy to combat multidrug-resistant lung infections.     

Analysis of the etiological structure and dynamics of antibiotic resistance in the causative agents of suppurative inflammatory diseases in the patients at a large general hospital

The structure of the causative agents isolated from patients with pyoinflammatory infections in 1980-1983 was analysed. It was shown that the surgical and urological infections were mainly caused by gram-negative bacteria. The other pyoinflammatory infections were mainly due to gram-positive cocci. A relatively high frequency of the strains of gram-negative bacteria, especially among Pseudomonas spp. and Enterobacter spp., resistant to aminoglycoside antibiotics, such as gentamicin, sisomycin and tobramycin with preserved sensitivity to amikacin and netilmicin in the majority of the strains was shown. Among the beta-lactam antibiotics cephotaxim and cephalotin were most active against gram-negative bacteria and staphylococci, respectively. The majority of the antibiotic resistant strains of gram-negative bacteria had analogous structures and levels of resistance to 7-12 antibiotics which might indicate the occurrence of 1-2 resistance plasmids among the clinical strains.     

Clinical presentation and significance of emerging opportunistic infections

In recent years the clinical face of the Acquired Immune Deficiency Syndrome has changed significantly as a consequence of use of prophylaxis against Pneumocystis carinii pneumonia and combination antiretroviral therapy. In this context several opportunistic pathogens have emerged as causes of clinically important disease. Many of these infective agents have previously been defined by specific geographical locations. Their clinical presentation frequently mimics other (non) opportunistic infections with which they may co-exist. The diagnosis is frequently delayed as the diagnostic possibility may not be in the clinician's differential diagnosis. Invasive procedures are frequently required in order to secure a diagnosis. Despite treatment, prognosis is often poor. Clinicians should be aware of these opportunistic pathogens in order that a timely diagnosis may be made and appropriate therapy given.     

DNA methylation pattern of CALCA in preterm neonates with bacterial sepsis as a putative epigenetic biomarker

Diagnosis of bacterial sepsis in preterm neonates can be difficult when using serum markers that rely on physiological changes because these changes may not necessarily be the result of bacterial infections alone. This retrospective investigation explores the potential use of the DNA methylation pattern of CpG sites in the promoter region of the calcitonin-related polypeptide α (CALCA) gene as an epigenetic biomarker for bacterial sepsis in preterm newborns. Four novel changes in the DNA methylation of eight CpG sites were detected in this gene and are present only in neonates with bacterial sepsis: (1) partial methylation at -769 CpG in gram-negative or gram-positive early onset sepsis (EOS) and late onset sepsis (LOS) episodes; (2) demethylation of 8 CpGs in gram-negative EOS followed by LOS (ELS) and in gram-negative EOS; (3) demethylation of 7 CpGs in gram-positive ELS and gram-positive EOS; (4) -771 C:G > T:A; 5′ de novo -778 CpG mutation on both alleles in EOS. These changes were not detected in birth weight and gestational age matched controls or in newborns with isolated infections. Our results indicate that the DNA methylation pattern of the promoter region of the CALCA gene varies in different types of bacterial preterm sepsis, thus suggesting a potential use as an epigenetic biomarker. A prospective confirmation of these results is essential.     

Occurrence of beta-lactamase type ESBL in rods of the Serratia species

Serratia spp. has been identified as an important opportunistic pathogen agent in nosocomial infections. The aim of the study was the determination of extended spectrum beta-lactamases (ESBL) occurrence among 78 of Serratia spp. strains isolated in 1996-1998 from clinical specimens obtained from patients of State Clinical Hospital in Bydgoszcz. Identification of Serratia spp. strains was performed in automatic ATB system with ID 32GN strips (bioMérieux). The strains with ESBL activity were detected by double-disc method according to Jarlier et al. (10) with small modifications. Clavulanic acid, tazobactam and sulbactam were used as the inhibitors of ESBLs. Drug-susceptibility was determined by disc-diffusion method according to NCCLS standards. Forty-five (57.7%) of the strains were ESBL (+). All of them belonged to S. marcescens species. The majority--91.1% of strains was derived from urine, 3 from wound and 1 from blood. The obtained results indicate the necessity of monitoring of ESBL-producing strains among gram-negative rods from clinical specimen. The aims of such a procedure are to control and to prevent their dissemination within hospital, as well as to avoid therapeutic failures.     

TL, the new bacteriophage of Pseudomonas aeruginosa and its application for the search of halo-producing bacteriophages

The properties of new virulent bacteriophage TL of Pseudomonas aeruginosa belonging to the family Podoviridae (genome size of 46 kb) were investigated. This bacteriophage is capable of lysogenizing the bacterial lawn in halo zones around negative colonies (NC) of other bacteriophages. TL forms large NC, that are hardly distinguishable on the lawn of P. aeruginisa PAO1. At the same time, on the lawns of some phage-resistant PAO1 mutants, as well as on those produced by a number of clinical isolates, TL forms more transparent NC. It is suggested that more effective growth of the bacteriophage TL NC is associated with the differences in outer lipopolysaccharide (LPS) layer of the cell walls of different bacterial strains, as well as of the bacteria inside and outside of the halos. This TL property was used to optimize selection of bacteriophages producing halos around NC on the lawn of P. aeruginosa PAO1. As a result, a group of bacteriophages differing in the patterns of interaction between their halos and TL bacteriophage, as well as in some characters was identified. Taking into consideration the importance of cell-surfaced structures of P. aeruginosa in manifestation of virulence and pathogenicity, possible utilization of specific phage enzymes, polysacchadide depolymerases, for more effective treatment of P. aeruginosa infections is discussed.     

Therapeutic bacteriophages as a rescue treatment for drug-resistant infections – an in vivo studies overview

Bacteriophages, highly prevalent in all environments, have found their use in medicine as an alternative or complement to antibiotics. The therapeutic use of bacteriophages was particularly popular in the 1920s and 1930s, until the discovery and introduction of antibiotics. Due to the dynamic growth of antibiotic resistance among bacterial strains, numerous international institutions (such as the FDA) have declared the search for novel treatment modalities to be of the highest priority. To date, bacteriophage therapy has not been registered for general use in Western countries. The regulation of biological medicinal products (within medicinal product regulation) does not contain a specific documentation frame for bacteriophages (only for vaccines, blood derived products, etc.) which, as active substances, need to meet specific requirements. Recently, the FDA allowed bacteriophage therapy to be used in the United States, via the Emergency Investigational New Drug scheme; clinical trials to compare the safety and efficacy of bacteriophage therapy are also permitted. To date, several therapeutic products of this type have made it to phase I or II; some clinical programmes have also been completed. This article cites numerous animal model studies and registered clinical trials, showing the safety and effectiveness of bacteriophage therapy, including infections caused by bacterial strains resistant to antibiotic treatment.     

Complete Genome Sequence of Bacteriophage BC-611 Specifically Infecting Enterococcus faecalis Strain NP-10011

Enterococcus faecalis is an opportunistic pathogen that causes serious infections in humans and animals and is also an important bacterium for dairy and probiotic supplement production. Therefore, bacteriophages infecting E. faecalis may be useful for phage therapy against multidrug-resistant strains or may threaten industrial fermentation. We isolated a virulent Siphoviridae bacteriophage, BC-611, specifically infecting E. faecalis strain NP-10011 but not infecting other E. faecalis strains or other enterococci. Although the genome sequence of BC-611 resembled that of enterococcal bacteriophage SAP6, BC-611 was marked by its narrow host specificity.     

Burkholderia cepacia complex bacteria: opportunistic pathogens with important natural biology

Interaction with plants around their roots and foliage forms the natural habitat for a wide range of gram-negative bacteria such as Burkholderia, Pseudomonas and Ralstonia. During these interactions many of these bacteria facilitate highly beneficial processes such as the breakdown of pollutants or enhancement of crop growth. All these bacterial species are also capable of causing opportunistic infections in vulnerable individuals, especially people with cystic fibrosis (CF). Here we will review the current understanding of the Burkholderia cepacia complex (Bcc) as a group of model opportunistic pathogens, contrasting their clinical epidemiology with their ecological importance. Currently, the B. cepacia complex is composed of nine formally named species groups which are all difficult to identify using phenotypic methods. Genetic methods such as 16S rRNA and recA gene sequence analysis have proven useful for Bcc species identification. Multilocus sequence typing (MLST) is also emerging as a very useful tool for both Bcc strain and species identification. Historically, Burkholderia cenocepacia was the most dominant Bcc pathogen in CF, however, probably as a result of strict infection control practices introduced to control the spread of this species, its prevalence has been reduced. Burkholderia multivorans is the now the most dominant Bcc infection encountered in the UK CF population, a changing epidemiology that also appears to be occurring in the US CF population. The distribution of Bcc species residing in the natural environment may vary considerably with the type of environment examined. Clonally identical Bcc strains have been found to occur in the natural environment and cause infection. The contamination of medical devices, disinfectants and pharmaceutical formulations has also been directly linked to several outbreaks of infection. In the last 10 years considerable progress has been made in understanding the natural biology and clinical infections caused by this fascinating group of bacteria.     

Bacteriophages and bacteriophage‐derived endolysins as potential therapeutics to combat Gram‐positive spore forming bacteria

Since their discovery in 1915, bacteriophages have been routinely used within Eastern Europe to treat a variety of bacterial infections. Although initially ignored by the West due to the success of antibiotics, increasing levels and diversity of antibiotic resistance is driving a renaissance for bacteriophage‐derived therapy, which is in part due to the highly specific nature of bacteriophages as well as their relative abundance. This review focuses on the bacteriophages and derived lysins of relevant Gram‐positive spore formers within the Bacillus cereus group and Clostridium genus that could have applications within the medical, food and environmental sectors.     

Immunochemotherapy of infants in the first year of life with intestinal infections due to opportunistic gram-negative aerobic bacteria]

The clinical and microbiological observations of 50 babies of the 1st year of age with intestinal infections due to opportunistic organisms were made. The babies were treated with antibacterial drugs and an immunoglobulin preparation. It was shown that the combined use of antibacterial and immunological preparations in the treatment of the babies with the intestinal infections caused by opportunistic organisms provided their earlier clinical recovery and lowered the unfavourable effect of the antibacterial drugs on the intestinal microflora.     

Idiopathic CD4 lymphocytopenia: a case of missing, wandering or ineffective T cells

Idiopathic CD4 lymphocytopenia (ICL) is a presumed heterogenous syndrome with key element low CD4 T-cell counts (below 300/mm³) without evidence of HIV infection or other known immunodeficiency. The etiology, pathogenesis, and management of ICL remain poorly understood and inadequately defined. The clinical presentation can range from serious opportunistic infections to incidentally diagnosed asymptomatic individuals. Cryptococcal and non-tuberculous mycobacterial infections and progressive multifocal leukoencephalopathy are the most significant presenting infections, although the spectrum of opportunistic diseases can be similar to that in patients with lymphopenia and HIV infection. Malignancy is common and related to opportunistic pathogens with an oncogenic potential. Autoimmune diseases are also seen in ICL with an increased incidence. The etiology of ICL is unknown. Mechanisms implicated in CD4 reduction may include decreased production, increased destruction, and tissue sequestration. New distinct genetic defects have been identified in certain patients with ICL, supporting the hypothesis of the lack of a common etiology in this syndrome. The management of ICL is focused on the treatment of opportunistic infections, appropriate prophylactic antibiotics, and close monitoring. In selected patients with life-threatening infections or profound immunodeficiency, strategies to increase T-cell counts or enhance immune function could be considered and have included interleukin-2, interferon-gamma, interleukin-7, and hematopoietic stem cell transplantation. The prognosis is influenced by the accompanying opportunistic infections and may be affected by publication bias of severe cases with unfavorable outcomes. As newer laboratory investigation techniques are being developed and targeted experimental treatments become available, our comprehension and prognosis of this rare syndrome could be significantly improved.Idiopathic CD4 lymphocytopenia (ICL) was described in 1992 as an immunodeficiency syndrome characterized by opportunistic infections and low CD4 T-cell counts in the absence of HIV infection. Despite the 20 years that have elapsed, the clinical spectrum, pathogenesis, and possible treatment for ICL remain obscure. Here, we attempt to summarize the salient features of this condition on the basis of the available literature to date.     

Sequencing and analysis of the cos region of the lactococcal bacteriophage c2

The cohesive termini of the DNA genome of the lactococcal bacteriophage c2 were directly sequenced and appeared to be complementary, non-symmetrical, 9-nucleotide single-stranded, 3′ extended DNAs, with the following sequence: 5′-GTTAGGCTT-3′ 3′-CAATCCGAA-5′. DNA located on either side of the cohesive ends was sequenced and several repeats and a region with the potential for a DNA bend were found. Previously sequenced cos regions of 13 other bacteriophages were also examined for similar sequence features. All of the bacteriophages from gram-positive hosts had 3′ extended DNA termini, in contrast to the bacteriophages from gram-negative hosts, which had 5′ extended DNA termini. All bacteriophages had a region of dyad symmetry close to the cohesive termini. A 7.3 kb DNA fragment of the c2 genome containing the cos sequences was cloned; transduction experiments demonstrated that these cloned sequences could act as a substrate for packaging enzymes of phage c2.     

Opportunistic infections in immunologically compromised nonhuman primates

Despite advances in the husbandry of nonhuman primates, natural and experimentally induced diseases continue to pose risks to animal health. These risks are particularly important when such disease results in immunodeficient states that provide an opportunity for the development of opportunistic infections. Because opportunistic agents may serve as significant confounders to research and hold potential for zoonotic transmission, knowledge of disease pathogenesis, surveillance, and risk reduction is particularly important to individuals who work closely with primates. Endogenous diseases of primates that result in blunted immune responses and thus allow for the development of opportunistic infection include simian type D retroviruses and measles. In addition, simian immunodeficiency virus is a frequently studied experimental cause of immunosuppression. This article focuses on clinical and pathological aspects of the most common opportunistic infections that occur in nonhuman primates maintained in research settings. The complete elimination of all infectious agents from primate colonies may be impossible and unwarranted, but microbial surveillance programs can help both to define the complement of agents present in a colony and to elucidate their potential impacts on colony health, zoonotic risk, and experimental research. We discuss risk reduction through the use of quarantine procedures, specific pathogen-free animals, and environmental controls.