Antibiotic therapy of acute dysentery in children with immunologic deficiency conditions

One hundred children with acute Sonnei and flexneri dysentery were followed up with respect to the infection process and main immunity indices. In 32 children the immunity indices were physiological (group 1) and in 68 children secondary immune deficiency was observed (group 2). The children were treated with aminoglycoside antibiotics and prodigiozan and it was stated that the time of recovery in the children with immune deficiency was longer by 5.2 days as compared to that in the children without immune deficiency. In the children with immune deficiency the combined use of one of the aminoglycosides, prodigiozan and lysozyme, led to a reduction of the host immunological reactivity and recovery within the same periods as those recorded for children with the physiological immunity status. It is recommended to use the antibiotic combination with prodigiozan and lysozyme in the treatment of all the forms of dysentery in children with secondary immune deficiency.     

Value of determining the spectrum of blood serum fatty acids in evaluating increasing the effectiveness of antibiotic therapy of dysentery in children with prodigiozan and ephedrine

One hundred and ninety one children with acute Sonne and Flexner dysentery were observed with respect to the disease process, immunity indices and blood serum fatty acid spectrum. 104 children were treated with monomycin alone and 87 children were treated with the antibiotic in combination with prodigiozan and ephedrine as immunostimulators. It was shown that the recovery terms in the patients treated with the use of the immunostimulators decreased as compared to the patients treated with the antibiotic alone. The fatty acid spectrum in the children treated with the use of the immunostimulators differed from that in the children treated without them by low levels of fatty acids of the C12:0 to C18:1 composition.     

Wheeze in preschool age is associated with pulmonary bacterial infection and resolves after antibiotic therapy

Background

Neonates with airways colonized by Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis are at increased risk for recurrent wheeze which may resemble asthma early in life. It is not clear whether chronic colonization by these pathogens is causative for severe persistent wheeze in some preschool children and whether these children might benefit from antibiotic treatment. We assessed the relevance of bacterial colonization and chronic airway infection in preschool children with severe persistent wheezing and evaluated the outcome of long-time antibiotic treatment on the clinical course in such children.

Methodology/Principal Findings

Preschool children (n = 42) with severe persistent wheeze but no symptoms of acute pulmonary infection were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Differential cell counts and microbiological and virological analyses were performed on BAL samples. Patients diagnosed with bacterial infection were treated with antibiotics for 2–16 weeks (n = 29). A modified ISAAC questionnaire was used for follow-up assessment of children at least 6 months after bronchoscopy. Of the 42 children with severe wheezing, 34 (81%) showed a neutrophilic inflammation and 20 (59%) of this subgroup had elevated bacterial counts (≥10⁴ colony forming units per milliliter) suggesting infection. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis were the most frequently isolated species. After treatment with appropriate antibiotics 92% of patients showed a marked improvement of symptoms upon follow-up examination.

Conclusions/Significance

Chronic bacterial infections are relevant in a subgroup of preschool children with persistent wheezing and such children benefit significantly from antibiotic therapy.     

Various methods of using lincomycin for treating acute and chronic hematogenic osteomyelitis in children]

Comparative data on the treatment of 209 children with acute and chronic hematogenic osteomyelitis are presented; 128 patients hospitalized before 1974 were treated with antibiotics, mainly penicillin and streptomycin without sensitivity testing. From 1974 81 children were treated with lincomycin; 80 per cent of the isolates were sensitive to this antibiotic. In lincomycin therapy the method of electrophoresis on the disease focus, intrabone administration of the drug and administration of the drug into the bone cavity together with the blood clot during surgical interventions in cases with chronic hematogenic osteomyelitis were used. A marked decrease in the rate of the chronic forms of the disease was registered (from 77.2 to 8.8 per cent).     

Ecological Application of Antibiotics as Respiratory Inhibitors of Bacterial Populations

Two terregenous and four marine bacterial isolates were treated with six antibiotics and antibiotic combinations. Comparisons made between responses of cells in early and late logarithmic and stationary growth phases indicated variable sensitivity to the agents. Bacteria in stationary and late log-phase cultures exhibited the greatest resistance, whereas the early log-phase cells exhibited greatest antibiotic susceptibility. We conclude that the tested antibiotics cannot be used for ecological purposes to delineate bacterial respiration in mixed microbial communities.     

Antibody‐mediated crosslinking of gut bacteria hinders the spread of antibiotic resistance

The body is home to a diverse microbiota, mainly in the gut. Resistant bacteria are selected by antibiotic treatments, and once resistance becomes widespread in a population of hosts, antibiotics become useless. Here, we develop a multiscale model of the interaction between antibiotic use and resistance spread in a host population, focusing on an important aspect of within‐host immunity. Antibodies secreted in the gut enchain bacteria upon division, yielding clonal clusters of bacteria. We demonstrate that immunity‐driven bacteria clustering can hinder the spread of a novel resistant bacterial strain in a host population. We quantify this effect both in the case where resistance preexists and in the case where acquiring a new resistance mutation is necessary for the bacteria to spread. We further show that the reduction of spread by clustering can be countered when immune hosts are silent carriers, and are less likely to get treated, and/or have more contacts. We demonstrate the robustness of our findings to including stochastic within‐host bacterial growth, a fitness cost of resistance, and its compensation. Our results highlight the importance of interactions between immunity and the spread of antibiotic resistance, and argue in the favor of vaccine‐based strategies to combat antibiotic resistance.     

支原体肺炎患儿细胞免疫功能及肺功能状态变化的临床研究

目的:研究支原体肺炎患儿细胞免疫及肺功能状态的变化情况。方法:选取2014年10月~2015年10月于本院进行诊治的68例支原体肺炎患儿为观察组,以同期68名体检健康儿童为对照组。观察并比较两组儿童的细胞免疫及肺功能,以及不同程度肺炎患儿的细胞免疫及肺功能指标。结果:观察组患儿细胞免疫指标及肺功能指标均低于对照组,差异具有统计学意义(P0.05);观察组重度肺炎患儿的细胞免疫指标及肺功能指标均低于中度及轻度患儿,差异具有统计学意义(P0.05);观察组中度肺炎患儿的细胞免疫指标及肺功能指标均低于轻度患儿,差异具有统计学意义(P0.05)。结论:支原体肺炎患儿细胞免疫及肺功能呈异常状态,且不同严重程度肺炎患儿的差异明显。     

Effectiveness of tobramycin in young children with Salmonella infection

The intestinal form of salmonellosis caused by S. typhimurium and the host immunity were studied in 108 infants. 60 infants were treated with ampicillin and the other 48 infants with tobramycin. The recovery period in patients treated with tobramycin was 8 days less as compared to the patients treated with ampicillin After discontinuation of the tobramycin use the pathogen was not detected in the repeated platings. Bactericidal function of neutrophils in these patients returned to normal within 15 days after the beginning of the treatment. Tobramycin was shown to be a highly active antibiotic in the treatment of salmonellosis of infants. No side effects were observed.     

Treatment of dysentery in children with a combination of monomycin and Eleutherococcus]

An acute dysentery process was studied in 100 children at the age of 1 to 14 years treated with monomycin; 54 patients (the 1st group) were treated with monomycin in combination with eleuterococcus and 46 patients (the 2nd group) were treated with monomycin alone. The dysentery process in the both groups was close. However, the increase in the levels of gamma-globulin, antidysentery antibodies and the phases of changes in the index of phagocytosis completeness during the disease were more pronounced in the patients of the 2nd group than those in the children of the 1st group. Recovery of the patients of the 1st group was registered earlier. It was concluded that eleuterococcus as an adaptagen provided recovery of the patients at lower efforts of the protection mechanisms. Wide use of eleuterococcus in combination with monomycin for the treatment of children with dysentery is recommended.     

Plasmodium falciparum variant surface antigen expression varies between isolates causing severe and nonsevere malaria and is modified by acquired immunity

In areas of endemic parasite transmission, protective immunity to Plasmodium falciparum malaria is acquired over several years with numerous disease episodes. Acquisition of Abs to parasite-encoded variant surface Ags (VSA) on the infected erythrocyte membrane is important in the development of immunity, as disease-causing parasites appear to be those not controlled by preexisting VSA-specific Abs. In this work we report that VSA expressed by parasites from young Ghanaian children with P. falciparum malaria were commonly and strongly recognized by plasma Abs from healthy children in the same area, whereas recognition of VSA expressed by parasites from older children was weaker and less frequent. Independent of this, parasites isolated from children with severe malaria (cerebral malaria and severe anemia) were better recognized by VSA-specific plasma Abs than parasites obtained from children with nonsevere disease. This was not due to a higher infection multiplicity in younger patients or in patients with severe disease. Our data suggest that acquisition of VSA-specific Ab responses gradually restricts the VSA repertoire that is compatible with parasite survival in the semi-immune host. This appears to limit the risk of severe disease by discriminating against the expression of VSA likely to cause life-threatening complications, such as cerebral malaria and severe anemia. Such VSA seem to be preferred by parasites infecting a nonimmune host, suggesting that VSA expression and switching are not random, and that the VSA expression pattern is modulated by immunity. This opens the possibility of developing morbidity-reducing vaccines targeting a limited subset of common and particularly virulent VSA.     

Does PGE1 Vasodilator Prevent Orthopaedic Implant-Related Infection in Diabetes? Preliminary Results in a Mouse Model

Background

Implant-related infections are characterized by bacterial colonization and biofilm formation on the prosthesis. Diabetes represents one of the risk factors that increase the chances of prosthetic infections because of related severe peripheral vascular disease. Vasodilatation can be a therapeutic option to overcome diabetic vascular damages and increase the local blood supply. In this study, the effect of a PGE₁ vasodilator on the incidence of surgical infections in diabetic mice was investigated.

Methodology

A S. aureus implant-related infection was induced in femurs of diabetic mice, then differently treated with a third generation cephalosporin alone or associated with a PGE₁ vasodilator. Variations in mouse body weight were evaluated as index of animal welfare. The femurs were harvested after 28 days and underwent both qualitative and quantitative analysis as micro-CT, histological and microbiological analyses.

Results

The analysis performed in this study demonstrated the increased host response to implant-related infection in diabetic mice treated with the combination of a PGE₁ and antibiotic. In this group, restrained signs of infections were identified by micro-CT and histological analysis. On the other hand, the diabetic mice treated with the antibiotic alone showed a severe infection and inability to successfully respond to the standard antimicrobial treatment.

Conclusions

The present study revealed interesting preliminary results in the use of a drug combination of antibiotic and vasodilator to prevent implant-related Staphylococcus aureus infections in a diabetic mouse model.     

血清HBP和PTX3在重度脑损伤继发性肺部细菌性感染 诊断中的应用价值

目的探讨血清肝素结合蛋白(HBP)与正五聚蛋白3(PTX3)对重度脑损伤继发性肺部细菌性感染的诊断价值。方法选择2015年3月至2019年1月我院重症医学科收治的重型颅脑损伤患者96例,对所有患者进行肺部感染情况判断,将出现继发性肺部细菌感染的患者纳入感染组,未出现继发性肺部细菌感染的患者纳入未感染组。分别检测两组患者入院后第1、3、5、7天的HBP、PTX3、白细胞(WBC)和C反应蛋白(CRP)水平,探讨其对于重度脑损伤患者继发肺部细菌感染的诊断价值,并对HBP、PTX3与WBC、CRP的相关性进行分析。结果共有39例重度脑损患者纳入感染组,57例患者纳入未感染组,患者肺部细菌感染的发生率为40.6%。入院第1天感染组患者HBP、WBC及CRP水平明显高于未感染组,同时入院后第3、5、7天时感染组患者HBP、PTX3、WBC、CRP水平均显著高于未感染组,差异均具有统计学意义(均P0.05)。单独采用HBP或PTX3对重度脑损伤继发性肺部细菌性感染进行诊断的约登指数为0.586和0.655,诊断的敏感性、特异性、阳性预测值、阴性预测值为74.3%、84.2%、76.3%、82.7%和79.5%、86.0%、79.5%、86.0%。联合检测的约登指数为0.776,诊断的敏感性、特异性、阳性预测值、阴性预测值为84.6%、93.4%、89.2%、89.8%。Spearman相关性分析显示HBP、PTX3水平与CRP水平均呈正线性相关(r=0.362、0.284,均P0.05)。结论 HBP和PTX3均为重度脑损伤患者继发肺部细菌感染诊断的敏感指标,联合检测能够提高其检测价值,对重度脑损伤患者肺部感染的早期诊断具有一定临床意义。     

Prodigiozan aerosols in the treatment of nonspecific respiratory organ diseases in children]

High efficacy of prodigiozan, a bacterial polysaccharide used in the form of inhalation in combined therapy of 123 children at the age of 3 to 14 with nonspecific bronchopulmonary pathologic conditions was shown. The drug was administered by means of inhalators UI-I and PAI-I once every 4--5 days in the form of 0.02 per cent solution prepared in situ. The single and the course doses were 100--400 and 300--2000 micrograms respectively. The positive therapeutic effect was observed in 85.0 per cent of the patients: improvement of the patient state was registered 4--6 days earlier than that in the control group, the indices of the respiration mechanics and nonspecific immunity (titers of lysozyme and complement) also improved. The rate of viral respiratory diseases among the children treated with prodigiozan decreased 2.5 times. High efficacy and physiological character of the aerosol method for administration of prodigiozan used the the first time in pediatry provided its recommendation for wide use.     

Anti-invasive activity of bovine lactoferrin towards group A streptococci.

Group A streptococci (GAS) are able to invade cultured epithelial and endothelial cells without evidence of intracellular replication. GAS, like other facultative intracellular bacterial pathogens, evolved such ability to enter and to survive within host cells avoiding the host defences, and bacterial intracellular survival could explain the recurrence of infections. We report here that 1 mg bovine lactoferrin (bLf)/mL significantly hindered the in vitro invasion of cultured epithelial cells by GAS isolated from patients suffering from pharyngitis and completely inhibited the invasiveness of GAS pretreated with subinhibiting concentrations of erythromycin or ampicillin. One milligram of bLf per millilitre was also able to increase the number of epithelial cells undergoing apoptosis following GAS invasion, although the number of intracellular GAS in the presence of bLf decreased by about 10-fold. The ability of bLf to decrease GAS invasion was confirmed by an in vivo trial carried out on 12 children suffering from pharyngitis and already scheduled for tonsillectomy. In tonsil specimens from children treated for 15 days before tonsillectomy with both oral erythromycin (500 mg t.i.d. (three times daily)) and bLf gargles (100 mg t.i.d.), a lower number of intracellular GAS was found in comparison with that retrieved in tonsil specimens from children treated with erythromycin alone (500 mg t.i.d.).     

In vivo and in vitro characterization of overproduced colicin E9 immunity protein.

We report the overproduction of the immunity protein for the DNase colicin E9 and its characterization both in vivo and in vitro. The genes for colicin immunity proteins are normally co-expressed from Col plasmids with their corresponding colicins. In the context of the enzymatic colicins, the two proteins form a complex, thereby protecting the host bacterium from the antibiotic activity of the colicin. This complex is then released into the medium, whereupon the colicin alone translocates (through the appropriate receptor) into sensitive bacterial strains, resulting in bacterial cell death. The immunity protein for colicin E9 (Im9) has been overproduced in a bacterial host in the absence of its colicin, to enable sufficient material to be isolated for structural studies. As a prelude to such studies, the in-vivo and in-vitro properties of overproduced Im9 were analysed. Electrospray mass spectrometry verified the molecular mass of the purified protein and analytical ultracentrifugation indicated that the native protein approximates a symmetric monomer. Fluorescence-enhancement and gel-filtration experiments show that purified Im9 binds to colicin E9 in a 1:1 molar ratio and that this binding neutralizes the DNase activity of the colicin. These results lay the foundations for a full biophysical and structural characterization of the colicin E9 DNase inhibitor protein, Im9.     

Pentraxin 3 (PTX3) Is Associated with Severe Sepsis and Fatal Disease in Emergency Room Patients with Suspected Infection: A Prospective Cohort Study

Background

Early diagnostic and prognostic stratification of patients with suspected infection is a difficult clinical challenge. We studied plasma pentraxin 3 (PTX3) upon admission to the emergency department in patients with suspected infection.

Methods

The study comprised 537 emergency room patients with suspected infection: 59 with no systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 67 with bacterial infection without SIRS (group 2), 54 with SIRS without bacterial infection (group 3), 308 with sepsis (SIRS and bacterial infection) without organ failure (group 4) and 49 with severe sepsis (group 5). Plasma PTX3 was measured on admission using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA).

Results

The median PTX3 levels in groups 1–5 were 2.6 ng/ml, 4.4 ng/ml, 5.0 ng/ml, 6.1 ng/ml and 16.7 ng/ml, respectively (p<0.001). The median PTX3 concentration was higher in severe sepsis patients compared to others (16.7 vs. 4.9 ng/ml, p<0.001) and in non-survivors (day 28 case fatality) compared to survivors (14.1 vs. 5.1 ng/ml, p<0.001). A high PTX3 level predicted the need for ICU stay (p<0.001) and hypotension (p<0.001). AUC^ROC in the prediction of severe sepsis was 0.73 (95% CI 0.66–0.81, p<0.001) and 0.69 in case fatality (95% CI 0.58–0.79, p<0.001). PTX3 at a cut-off level for 14.1 ng/ml (optimal cut-off value for severe sepsis) showed 63% sensitivity and 80% specificity. At a cut-off level 7.7 ng/ml (optimal cut-off value for case fatality) showed 70% sensitivity and 63% specificity in predicting case fatality on day 28.In multivariate models, high PTX3 remained an independent predictor of severe sepsis and case fatality after adjusting for potential confounders.

Conclusions

A high PTX3 level on hospital admission predicts severe sepsis and case fatality in patients with suspected infection.     

Correlative proteomics identify the key roles of stress tolerance strategies in Acinetobacter baumannii in response to polymyxin and human macrophages

The opportunistic pathogen Acinetobacter baumannii possesses stress tolerance strategies against host innate immunity and antibiotic killing. However, how the host-pathogen-antibiotic interaction affects the overall molecular regulation of bacterial pathogenesis and host response remains unexplored. Here, we simultaneously investigate proteomic changes in A. baumannii and macrophages following infection in the absence or presence of the polymyxins. We discover that macrophages and polymyxins exhibit complementary effects to disarm several stress tolerance and survival strategies in A. baumannii, including oxidative stress resistance, copper tolerance, bacterial iron acquisition and stringent response regulation systems. Using the spoT mutant strains, we demonstrate that bacterial cells with defects in stringent response exhibit enhanced susceptibility to polymyxin killing and reduced survival in infected mice, compared to the wild-type strain. Together, our findings highlight that better understanding of host-pathogen-antibiotic interplay is critical for optimization of antibiotic use in patients and the discovery of new antimicrobial strategy to tackle multidrug-resistant bacterial infections.     

Antibiotic therapy in children with pertussis]

The data accumulated within the last years required revision of the indications to the use of antibiotics in treatment of pertussis. One of the aims of antibiotic therapy in pertussis was to prevent colonization of B. pertussis in the respiratory tracts. With that end in view the choice of antibiotics should be limited by those, to which the pathogen is the most sensitive i.e. erythromycin, ampicillin and augmentin. Comparative efficacy of erythromycin and ampicillin during the first 2 weeks of the disease was studied in 79 infants at the age not older than 1 year with pertussis and it was shown that erythromycin was advantageous by its therapeutic activity and less side effects. Expedience of the antibiotic therapy during the spastic period for providing a preventive effect on development of bronchopulmonary complications was studied in 201 patients with pertussis. No preventive effect of the antibiotics on development of the bronchopulmonary complications defined by the secondary bacterial flora was recorded. In the group of the patients treated with the antibiotics prophylactically (group 1) the complications were 2.6 times more frequent than in the patients treated with pathogenetic agents alone (group 2). Intrahospital pneumonia developed in 8.9 per cent of the patients in group 1 and in 1.5 per cent of the patients in group 2. Therefore, antibiotics should not be used at the late periods of pertussis for prophylaxis of secondary bacterial complications.     

Modulation of Inflammatory Response in a Cirrhotic Rat Model with Induced Bacterial Peritonitis

Bacterial peritonitis is a severe complication in patients with cirrhosis and ascites and despite antibiotic treatment, the inflammatory response to infection may induce renal dysfunction leading to death. This investigation evaluated the effect of TNF-α blockade on the inflammatory response and mortality in cirrhotic rats with induced bacterial peritonitis treated or not with antibiotics. Sprague-Dawley rats with carbon-tetrachloride-induced cirrhosis were treated with an intraperitoneal injection of 10⁹ CFU of Escherichia coli diluted in 20 mL of sterile water to induce bacterial peritonitis and randomized to receive subcutaneously-administered placebo, ceftriaxone, anti-TNF-α mAb and ceftriaxone, or anti-TNF-α mAb alone. No differences were observed between groups at baseline in respect to renal function, liver hepatic tests, serum levels of nitrite/nitrate and TNF-α. Treatment with ceftriaxone reduced mortality (73.3%) but differences did not reach statistical significance as compared to placebo. Mortality in rats treated with ceftriaxone and anti-TNF-α mAb was significantly lower than in animals receiving placebo (53% vs. 100%, p<0.01). Serum TNF-α decreased significantly in surviving rats treated with ceftriaxone plus anti-TNF-α mAb but not in treated with antibiotics alone. Additional studies including more animals are required to assess if the association of antibiotic therapy and TNF-α blockade might be a possible approach to reduce mortality in cirrhotic patients with bacterial peritonitis.     

Why Children with Severe Bacterial Infection Die: A Population–Based Study of Determinants and Consequences of Suboptimal Care with a Special Emphasis on Methodological Issues

Introduction

Suboptimal care is frequent in the management of severe bacterial infection. We aimed to evaluate the consequences of suboptimal care in the early management of severe bacterial infection in children and study the determinants.

Methods

A previously reported population-based confidential enquiry included all children (3 months- 16 years) who died of severe bacterial infection in a French area during a 7-year period. Here, we compared the optimality of the management of these cases to that of pediatric patients who survived a severe bacterial infection during the same period for 6 types of care: seeking medical care by parents, evaluation of sepsis signs and detection of severe disease by a physician, timing and dosage of antibiotic therapy, and timing and dosage of saline bolus. Two independent experts blinded to outcome and final diagnosis evaluated the optimality of these care types. The effect of suboptimal care on survival was analyzed by a logistic regression adjusted on confounding factors identified by a causal diagram. Determinants of suboptimal care were analyzed by multivariate multilevel logistic regression.

Results

Suboptimal care was significantly more frequent during early management of the 21 children who died as compared with the 93 survivors: 24% vs 13% (p = 0.003). The most frequent suboptimal care types were delay to seek medical care (20%), under-evaluation of severity by the physician (20%) and delayed antibiotic therapy (24%). Young age (under 1 year) was independently associated with higher risk of suboptimal care, whereas being under the care of a paediatric emergency specialist or a mobile medical unit as compared with a general practitioner was associated with reduced risk.

Conclusions

Suboptimal care in the early management of severe bacterial infection had a global independent negative effect on survival. Suboptimal care may be avoided by better training of primary care physicians in the specifics of pediatric medicine.