Development Of Effective Antibiotics Research Articles

Probing the interaction between the metallo-β-lactamase SMB-1 and ampicillin by multispectral approaches combined with molecular dynamics.

Metallo-β-lactamases (MβLs) hydrolyze and inactivate β-lactam antibiotics, are a pivotal mechanism conferring resistance against bacterial infections. SMB-1, a novel B3 subclass of MβLs from Serratia marcescens could deactivate almost all β-lactam antibiotics including ampicillin (AMP), which has posed a serious threat to public health. To illuminate the mechanism of recognition and interaction between SMB-1 and AMP, various fluorescence spectroscopy techniques and molecular dynamics simulation were employed. The results of quenching spectroscopy unraveled that AMP could make SMB-1 fluorescence quenching that mechanism was the static quenching; the synchronous and three-dimensional fluorescence spectra validated that the microenvironment and conformation of SMB-1 were altered after interaction with AMP. The molecular dynamics results demonstrated that the whole AMP enters the binding pocket of SMB-1, even though with a relatively bulky R1 side chain. Loop1 and loop2 in SMB-1 undergo significant fluctuations, and α2 (71-73) and local α5 (186-188) were turned into random coils, promoting zinc ion exposure consistent with circular dichroism spectroscopy results. The binding between them was driven by a combination of enthalpy and entropy changes, which was dominated by electrostatic force in agreement with the fluorescence observations. The present study brings structural insights and solid foundations for the design of new substrates for β-lactamases and the development of effective antibiotics that are resistant to superbugs.

A systematic review on the WHO Global Priority Pathogens (GPP) List reported in animals, products, and by-products in Colombia

Background: The World Health Organization (WHO) published the Global Priority Pathogens (GPP) List for the Research and Development of Effective Antibiotics in 2017, a catalog of bacteria to be prioritized in the global fight against bacterial antibiotic resistance. Objective: To collect and app raise the scientific evidence on bacteria listed as GPP in animals and their products and by-products in Colombia, identifying knowledge gaps and providing finding-based recommendations. Materials and Methods: The review was carried out according to PRISMA guidelines. Only original articles published in peer35 reviewed journals were considered. Results: Twenty-one articles, published between 2001 and 2021, met the inclusion criteria. The geographical areas of study were the provinces of Antioquia, Cundinamarca —including Bogotá C.D., and Santander and Tolima. The main bacteria from the WHO´s list reported were fluoroquinolone-resistant Salmonella, methicillin-resistant and vancomycin-intermediate and resistant Staphylococcus aureus, and carbapenem-resistant ESBL-producing Enterobacteriaceae. The sources were feces, facilities, equipment, feed, animal drinking water, bed chip, tissues, and carcasses, related to broilers and laying hens, cattle, and pigs. Conclusions: Results obtained herein afford important advances in the knowledge of the phenomenon and its dynamic in Colombia. Nevertheless, much remains to be researched in the country, including standardized methods for the microbiological identification in veterinary medicine, as well as the evaluation of the antibiotic susceptibility patrons in bacteria in accordance with what is done in humans, among other aspects.

Optimisation and identification of anchovy antimicrobial peptides by enzymolysis and untargeted proteomic profiling

Natural antimicrobial peptides are promising antibiotics without inducing high bacteria resistance and have wide applications in the medical health and food industry. Herein, we prepared and optimised anchovy antimicrobial peptides (AAMPs) by degreasing and enzymolysis of anchovy extracts under different conditions. The enzymolysis mixtures at optimised preparation conditions exhibited concentration-dependent inhibitory activity against Staphylococcus aureus. Then, we applied the mass spectrometry-based proteomics analysis to globally profile the peptide constitutes within the active peptide mixture and finally, 4 unique peptides coming from 68 proteins were confidently identified. We compared the peptide sequences with the antimicrobial peptides (AMPs) database and synthesised 4 potential AAMPs. As a result, peptide GTEDELDKY exhibited inhibitory activity against Escherichia coli, and peptides DREGESGPS, YIGRPIPQ and YEDEINKR exhibited inhibitory activity against SA. Our work established a useful workflow for discovering novel AMPs from fish proteins, which may play important role in the development of effective antibiotics.

A short synthetic peptide, based on LyeTx I from Lycosa erythrognatha venom, shows potential to treat pneumonia caused by carbapenem-resistant Acinetobacter baumannii without detectable resistance.

The emergence of antibiotic-resistant bacteria, especially carbapenem-resistant Acinetobacter baumannii (CRAB), together with relative stagnation in the development of effective antibiotics, has led to enormous health and economic problems. In this study, we aimed to describe the antibacterial spectrum of LyeTx I mnΔK, a short synthetic peptide based on LyeTx I from Lycosa erythrognatha venom, against CRAB. LyeTx I mnΔK showed considerable antibacterial activity against extensively resistant A. baumannii, with minimum inhibitory and bactericidal concentrations ranging from 1 to 16 µM and 2 to 32 µM, respectively. This peptide significantly increased the release of 260 nm-absorbing intracellular material from CRAB, suggesting bacteriolysis. LyeTx I mnΔK was shown to act synergistically with meropenem and colistin against CRAB. The cytotoxic concentration of LyeTx I mnΔK against Vero cells (CC50 = 55.31 ± 5.00 µM) and its hemolytic activity (HC50 = 77.07 ± 4.00 µM) were considerably low; however, its antibacterial activity was significantly reduced in the presence of human and animal serum and trypsin. Nevertheless, the inhalation of this peptide was effective in reducing pulmonary bacterial load in a mouse model of CRAB infection. Altogether, these results demonstrate that the peptide LyeTx I mnΔK is a potential prototype for the development of new effective and safe antibacterial agents against CRAB.

Alchornea Cordifolia (Christmas Bush) Leaves Extract Shows Activity Against Extended-Spectrum Beta-Lactamase-Producing Klebsiella Pneumoniae That Cause Multi-Drug Resistant Urinary Tract Infections

Klebsiella pneumoniae are one of the most common cause of multi-drug resistant urinary tract infections such as cystitis and pyelonephritis. Extended-spectrum beta-lactamases are plasmid-mediated enzymes commonly found in the Klebsiella pneumoniae and other Gram negative bacteria . They are capable of hydrolysing beta-lactams except carbapenems and cephamycins. Extended-spectrum beta-lactamases also confer resistance to several non-beta-lactam antibiotics, limiting treatment options for urinary tract infections caused by extended-spectrum beta-lactamases -producing K. pneumoniae . This study determined the in vitro efficacy of Alchornea cordifolia on extended-spectrum beta-lactamases -producing K. pneumoniae . Serial dilutions of the ethanolic extract of the leaves were prepared and tested against the extended-spectrum-beta-lactamases-producing K. pneumoniae . The phytochemical screening was performed to determine the antibacterial compounds. The Christmas bush leaves extracts concentrations ranging from 50 mg/ml – 200 mg/ml showed significant active diameter zone of inhibition. The ethanolic extract of A. cordifolia leaves had minimum inhibition concentration and minimum bactericidal concentration of 3.13 mg/ml indicating significant antibiotic activity against the ESBL isolates. The phytochemical screening of the Christmas bush leaves showed the presence of antimicrobial phytochemicals such as flavonoids. Ethanolic extracts of Christmas bush leaves is proving to be efficacious against multi-drug resistant urinary tract infections. This offers hope for the development of effective antibiotics due to the presence of flavonoids in the A. cordifolia leaf extracts. Therefore, there is the need to determine the toxicological effect and clinical trials of the active antimicrobial compounds isolated in the leaf extracts of A. cordifolia shrub. Keywords: Alchornea. cordifolia, Flavonoids, Multi-drug resistant, Extended-spectrum beta-lactamase, Klebsiella pneumoniae DOI: 10.7176/JNSR/11-24-03 Publication date: December 31 st 2020

Tuberculosis sanatorium treatment at the advent of the chemotherapy era

BackgroundThe discovery of antibiotics in the mid-twentieth century marked a major transition in tuberculosis (TB) treatment and control. There are few studies describing the duration of TB disease and its treatment from the pre-chemotherapy era and little data on how these treatments changed in response to the development of effective antibiotics. The goal of this research is to understand how inpatient treatment for high incidence populations, the First Nations peoples of Saskatchewan, Canada, changed in response to increasing availability of antibiotics effective against TB. We expected that as treatment regimens transitioned from convalescence-only to triple antibiotic therapy, the length of inpatient treatment would shorten.MethodsAnalyses were performed on records of sanatoria admissions and discharges occurring between 1933 and 1959 in Saskatchewan, Canada. Year of antibiotic discovery was taken as a proxy for treatment regimen: no chemotherapy (pre-1944), mono-therapy (Streptomycin, 1944–1946), dual-therapy (Streptomycin and PAS, 1946–1952), and triple-therapy (Streptomycin, PAS, and INH 1952-). A pooled linear regression of log-transformed length of first admission as predicted by year of admission was modeled to assess the relationship between admission length and year of admission, corrected for clinical and demographic variables.ResultsFirst admission length increased 19% in the triple-therapy era as compared to the pre-chemotherapy era, from 316 days (10.4 months) to 377 days (12.4 months). After the discovery of INH (1952), we find statistically significant increases in the proportion of successfully completed therapies (0.55 versus 0.60, p = 0.035), but also in patients who left hospital against medical advice (0.19 versus 0.29, p < 0.0001), indicating that as hospitalizations lengthened, more patients chose to discharge without the sanction of their physician. The readmission rate increased from 10 to 50% of all admissions while the province-level TB-specific death rate fell from 63.1 per 10,000 in 1933 to 4.7 per 10,000 in 1958.ConclusionCounterintuitively, we find that the length of first admissions increased with the discovery of TB-treating antibiotics. Increasing admission volume and readmission rate indicate an intensification of inpatient TB treatment during this era. These analyses provide a novel estimate of the effect of changing treatment policy on sanatorium admissions in this population.

Antimicrobial Activity of Psidium Guajava (Guava) Leaves Extract on Extended-Spectrum Beta-Lactamase-Producing Klebsiella Pneumoniae that Cause Multi-Drug Resistant Urinary Tract Infections

Extended-spectrum beta-lactamases (ESBLs) are plasmid-mediated enzymes commonly found in the Enterobacteriaceae that are capable of hydrolysing s-lactams except carbapenems and cephamycins. ESBLs also confer resistance to several non-s-lactam antibiotics. ESBL producing isolates are predominantly Klebsiella pneumoniae and Eschericia coli . Klebsiella pneumoniae are one of the most common causes of urinary tract infections such as cystitis and pyelonephritis developed by about 150 million people in every given year. ESBL-producing Klebsiella pneumoniae appear susceptible to cephalosporins in vitro using conventional breakpoints but ineffective in vivo . This has limited treatment options for urinary tract infections caused by extended-spectrum beta-lactamases -producing K. pneumoniae . This study determined the in vitro efficacy of Psidium guajava on extended-spectrum beta-lactamases -producing K. pneumoniae using agar well diffusion and well microplate dilution method. Serial dilutions of the ethanolic extract of the leaves were prepared and tested against the extended-spectrum beta-lactamases-producing K. pneumoniae. The phytochemical screening was performed to determine the antibacterial compounds. The guava leaves extracts concentrations ranging from 50 mg/ml – 200 mg/ml showed active diameter zone of inhibition. The ethanolic extract of guava leaves had minimum inhibition concentration and minimum bactericidal concentration of 6.25mg/ml indicating significant antibiotic activity against the ESBL isolates. The phytochemical screening of the guava leaves showed the presence of antimicrobial phytochemicals such as flavonoids. Ethanolic extracts of guava leaves is proving to be efficacious against multi-drug resistant ESBL-producing K. pneumoniae , which a major cause urinary tract infections. This offers hope for the development of effective antibiotics against multi-drug resistant urinary tract infections due to the presence of flavonoids in the guava leaf extracts. Therefore, there is the need to determine the toxicological effect of the active antimicrobial compounds isolated in the leaf extracts of guava plant. Keywords : Psidium guajava , Flavonoids, Multi-drug resistant, Extended-spectrum beta-lactamase, Klebsiella pneumoniae DOI: 10.7176/JNSR/11-22-02 Publication date: November 30 th 2020

Iron-dependent essential genes in Salmonella Typhimurium

BackgroundThe molecular mechanisms underlying bacterial cell death due to stresses or bactericidal antibiotics are complex and remain puzzling. Due to the current crisis of antibiotic resistance, development of effective antibiotics is urgently required. Previously, it has been shown that iron is required for effective killing of bacterial cells by numerous bactericidal antibiotics.ResultsWe investigated the death or growth inhibition of S. Typhimurium under iron-restricted conditions, following disruption of essential genes, by transposon mutagenesis using transposon sequencing (Tn-seq). Our high-resolution Tn-seq analysis revealed that transposon mutants of S. Typhimurium with insertions in essential genes escaped immediate killing or growth inhibition under iron-restricted conditions for approximately one-third of all previously known essential genes. Based on this result, we classified all essential genes into two categories, iron-dependent essential genes, for which the insertion mutants can grow slowly if iron is restricted, and iron-independent essential genes, for which the mutants become nonviable regardless of iron concentration. The iron-dependency of the iron-dependent essential genes was further validated by the fact that the relative abundance of these essential gene mutants increased further with more severe iron restrictions. Our unexpected observation can be explained well by the common killing mechanisms of bactericidal antibiotics via production of reactive oxygen species (ROS). In this model, iron restriction would inhibit production of ROS, leading to reduced killing activity following blocking of essential gene functions. Interestingly, the targets of most antibiotics currently in use clinically are iron-dependent essential genes.ConclusionsOur result suggests that targeting iron-independent essential genes may be a better strategy for future antibiotic development, because blocking their essential gene functions would lead to immediate cell death regardless of the iron concentration. This work expands our knowledge on the role of iron to a broad range of essential functions and pathways, providing novel insights for development of more effective antibiotics.

Probing transport of charged β-lactamase inhibitors through OmpC, a membrane channel from E. coli

One of the major causes of antibiotic resistance in the Gram-negative bacteria is the low permeability across the outer membrane. Currently a main bottleneck in the development of effective antibiotics is the lack of a general method to quantify permeation which would allow screening for optimal scaffolds. Here, we present a permeation assay based on conventional electrophysiology. The method mainly involves application of concentration gradients of charged molecules with different electrophoretic mobilities through a membrane channel. Thus the unbalanced flux creates an electrostatic potential which provides direct information on relative ion fluxes. The experimental approach applied here involves measuring zero-current-potentials and the corresponding single channel conductance. For OmpC and the β-lactamase inhibitor avibactam at a 10 μm gradient the calculated flux rate at Vm=0mV was about n=200 molecules/s per OmpC single pore.

Three Cases of Pediatric Neck Abscess

Neck abscess is a rarely encountered condition in children. Furthermore, the condition has been thought to have become even less common with the development of effective antibiotics. However, early detection and treatment of neck abscess is necessary, especially in children, as it may lead to airway narrowing or other potentially fatal complications. We report 3 cases of neck abscess, diagnosed by computed tomography (CT) in children with different clinical backgrounds: Kabuki make-up syndrome, Kawasaki disease, and acquired hemophilia. It is important to consider the nature of the underlying disease before deciding on surgical drainage of the abscess.

New Insights into Autoinducer-2 Signaling as a Virulence Regulator in a Mouse Model of Pneumonic Plague.

The Enterobacteriaceae family members, including the infamous Yersinia pestis, the causative agent of plague, have a highly conserved interbacterial signaling system that is mediated by the autoinducer-2 (AI-2) quorum-sensing molecule. The AI-2 system is implicated in regulating various bacterial virulence genes in diverse environmental niches. Deletion of the gene encoding the synthetic enzyme for the AI-2 substrate, luxS, leads to either no significant change or, paradoxically, an increase in in vivo bacterial virulence. We showed that deletion of the rbsA and lsrA genes, components of ABC transport systems that interact with AI-2, synergistically disrupted AI-2 signaling patterns and resulted in a more-than-50-fold decrease in Y.pestis strain CO92 virulence in a stringent pneumonic plague mouse model. Deletion of luxS or lsrK (encoding AI-2 kinase) from the ΔrbsA ΔlsrA background strain or complementation of the ΔrbsA ΔlsrA mutant with the corresponding gene(s) reverted the virulence phenotype to that of the wild-type Y.pestis CO92. Furthermore, the administration of synthetic AI-2 in mice infected with the ΔrbsA ΔlsrA ΔluxS mutant strain attenuated this triple mutant to a virulence phenotype similar to that of the ΔrbsA ΔlsrA strain in a pneumonic plague model. Conversely, the administration of AI-2 to mice infected with the ΔrbsA ΔlsrA ΔluxS ΔlsrK mutant did not rescue animals from lethality, indicating the importance of the AI-2-LsrK axis in regulating bacterial virulence. By performing high-throughput RNA sequencing, the potential role of some AI-2-signaling-regulated genes that modulated bacterial virulence was determined. We anticipate that the characterization of AI-2 signaling in Y.pestis will lead to reexamination of AI-2 systems in other pathogens and that AI-2 signaling may represent a broad-spectrum therapeutic target to combat antibiotic-resistant bacteria, which represent a global crisis of the 21st century. IMPORTANCEYersinia pestis is the bacterial agent that causes the highly fatal disease plague. The organism represents a significant concern because of its potential use as a bioterror agent, beyond the several thousand naturally occurring human infection cases occurring globally each year. While there has been development of effective antibiotics, the narrow therapeutic window and challenges posed by the existence of antibiotic-resistant strains represent serious concerns. We sought to identify novel virulence factors that could potentially be incorporated into an attenuated vaccine platform or be targeted by novel therapeutics. We show here that a highly conserved quorum-sensing system, autoinducer-2, significantly affected the virulence of Y.pestis in a mouse model of pneumonic plague. We also identified steps in autoinducer-2 signaling which had confounded previous studies and demonstrated the potential for intervention in the virulence mechanism(s) of autoinducer-2. Our findings may have an impact on bacterial pathogenesis research in many other organisms and could result in identifying potential broad-spectrum therapeutic targets to combat antibiotic-resistant bacteria, which represent a global crisis of the 21st century.

Using the rate of bacterial clearance determined by real-time polymerase chain reaction as a timely surrogate marker to evaluate the appropriateness of antibiotic usage in critical patients with Acinetobacter baumannii bacteremia*

Bacteremia caused by Acinetobacter baumannii is becoming more frequent among critically ill patients, and has been associated with high mortality and prolonged hospital stay. Multidrug resistance and delay in blood culture have been shown to be significant barriers to appropriate antibiotic treatment. Quantitative polymerase chain reaction assays were recently used to monitor bacterial loads; we hypothesized that the rate of bacterial clearance determined by quantitative polymerase chain reaction can be used as a timely surrogate marker to evaluate the appropriateness of antibiotic usage. Prospective observational study. University hospital and research laboratory. Patients with culture-proven A. baumannii bacteremia in the intensive care units were prospectively enrolled from April 2008 to February 2009. Plasmid Oxa-51/pCRII-TOPO, which contained a 431-bp fragment of the A. baumannii-specific Oxa-51 gene in a pCRII-TOPO vector, was used as the standard. Sequential bacterial DNA loads in the blood were measured by a quantitative polymerase chain reaction assay. We enrolled 51 patients with A. baumannii bacteremia, and examined 318 sequential whole blood samples. The initial mean bacterial load was 2.15 log copies/mL, and the rate of bacterial clearance was 0.088 log copies/mL/day. Multivariate linear regression using the generalized estimation equation approach revealed that the use of immunosuppressants was an independent predictor for slower bacterial clearance (coefficient, 1.116; p<.001), and appropriate antibiotic usage was an independent predictor for more rapid bacterial clearance (coefficient, -0.995; p<.001). Patients with a slower rate of bacterial clearance experienced higher in-hospital mortality (odds ratio, 2.323; p=.04) Immunosuppression and appropriate antibiotic usage were independent factors affecting the rate of clearance of A. baumannii bacteremia in critical patients. These findings highlight the importance of appropriate antibiotic usage and development of effective antibiotics against A. baumannii in an era of emerging antibiotic resistance. The rate of bacterial clearance could serve as a timely surrogate marker for evaluating the appropriateness of antibiotics.

Solitary renal actinomycosis.

A 53-year-old man, who was a recurrent stone former and diabetic, presented with left flank pain, pyuria, and fever. He had undergone multiple interventions for removal of the left kidney stones and retained ureteral double-J stent. All blood and urine investigations were unremarkable and negative for fungus and tuberculosis. Computed tomography scan revealed an edematous left kidney with poorly enhancing upper pole having dilated calyces with hyperdense contents suggestive of abscess (Figure 1). Ultrasonography-guided aspiration of left renal abscess grew Pseudomona Aeruginosa. Thereafter, patient underwent left laparoscopic nephrectomy. On gross examination, yellow sulfur granules in the dilated upper pole calyceal system were seen (Figure 2). Microscopic examination of the sulfur granules demonstrated homogenous eosinophilic hyaline material coating actinomyces colonies surrounded by a dense lymphoplasmacytic infiltrate (Splendore-Hoeppli phenomenon) with concomitant pyelonephritis (Figure 3). The patient was discharged on long-term doxycycline as he was allergic to penicillin. Solitary renal actinomycosis can present as pyelonephritis, renal/perinephric abscess, or renal mass. (1) Multiple interventions, recurrent urinary tract infection, retained double-J stent, uncontrolled diabetes mellitus, and untreated dental caries are predisposing factors for this disease. With development of effective antibiotics, the challenge now lies in the clinician’s ability to make the correct diagnosis, thus, ensuring timely recognition and renal salvage if possible. (2)

The Coming Plague: Newly Emerging Diseases in a World out of Balance

Laurie Garrett Virago, pounds sterling20, pp 750 ISBN 1 85381 764 3 Optimism that followed the development of effective antibiotics, vaccines, and ambitious public health programmes has been confounded by the emergence of new infectious diseases and resurgence of old ones, sometimes in impressive epidemics. The changing nature of infectious disease epidemiology results from the altered balance between host (humans), agent (the microbe), and environment; this is the subject matter of this excellent book by the American journalist Laurie Garrett. The Coming Plague describes for the nonspecialist what several recent official reports in the United States have documented for …

Percutaneous abscess drainage: current applications for critically ill patients.

Radiologically guided percutaneous abscess drainage (PAD) was first reported in 1977. Since this time, technological advances in imaging, improved catheter technology, and increased experience with the procedure have resulted in a tremendous expansion of the indications for PAD. This procedure currently has applications in nearly every organ system of the body. These changes have also contributed to improved success rates, with concurrent minimization of procedure-related complications. The advantages of PAD include simple, rapid performance; feasibility of bedside intensive care unit (ICU) performance; safety; avoidance of general anesthesia; and well-documented efficacy. This procedure has now become well entrenched in clinical medicine and probably ranks with the development of effective antibiotics as the most significant improvement in the treatment of abscesses in the past century. PAD is ideally suited for the treatment of critically ill ICU patients. We discuss technical developments over the past 15 years; general principles of patient preparation and catheters are also reviewed. Current applications of PAD in each organ system are discussed.

Dual application of Western and Kampo medicine in the treatment of intestinal diseases

As the development of effective antibiotics and synthetic drugs has almost eradicated many fatal infectious diseases, the most pressing problems in modern medicine are diseases which are closely related to functional and cellular degeneration and involve constitutional factors. Accordingly, in the treatment of these diseases, a therapeutic approach which recognizes individual differences and changes biological response through changes of cell function or properties is needed. For these reasons, Kampo drugs are frequently used in the treatment of intestinal diseases and post-operative hepatic injury, and for improvement of general patient condition after operation. In this presentation, I would like to report the treatment of intestinal diseases with combination of Western and Kampo medicine and to present the characteristics of Kampo drug and their differences from Western drugs.

University of California/Davis Interdepartmental Conference on Gram-Negative Septicemia

Gram-negative septicemia remains one of the most serious forms of hospital-acquired infection. The most consistently virulent component of the gram-negative lipopolysaccharide (endotoxin) appears to be lipid A. Elucidation of the structure-function relationships of lipid A and the biochemical configurations required for endotoxicity makes possible the design of lipopolysaccharide antagonists and/or the production of poly- or monoclonal antibodies that may abrogate the biologic effects of endotoxin. The mechanisms of activity of lipopolysaccharide and the pathophysiologic events it triggers are now better understood than in the recent past. Lipid A triggers the release of mediators such as cachectin (tumor necrosis factor), thereby initiating a cascade of potentially lethal events. Although recent studies indicate no routine role for corticosteroids in gram-negative septic shock or acute respiratory distress syndrome, considerable progress has been made in the development of effective antibiotics. Recent studies of septicemia in neutropenic patients show survival rates significantly higher than those reported more than two decades ago.

Clinical significance of antibiotic-resistant bacteria.

After a period of 14 years, antibiotics still pose problems to the clinician, and many of those problems are the result of antibiotic-resistant micro-organisms. Of course, some of the bacteria and most of the viruses and fungi have never been affected by antibiotics. Our attack on infections by those organisms consists in the development of effective antibiotics or other therapeutic agents or by measures designed to improve the host's defenses. In this paper we are concerned with some strains of bacteria that are inhibited by a certain antibiotic while other strains are not. That this does not include all of the bacteria that commonly cause infections in humans is shown in the table. Infections caused by the organisms in group 1 usually respond promptly to sufficient amounts of the proper antibiotics, and, although resistant forms have been produced with difficulty in vitro, these resistant forms have not been found in