Search

Enterococci are rarely implicated in the causation of pneumonia or lung abscess. Two patients are reported who developed large lung abscess cavities from enterococcal pneumonia. Combination penicillin and aminoglycoside antimicrobial therapy and drainage with a transthoracic tube resulted in complete cavity closure and healing. Enterococci should be considered as possible etiologic agents of pneumonia. Percutaneous chest tube drainage appears helpful in certain types of lung abscess.

The presence of supercoiled deoxyribonucleic acid in the form of a relaxation complex is described for the antibiotic resistance plasmids R64, R28K, and R6K. The properties of these relaxation complexes indicate that they consist of a covalently closed circular deoxyribonucleic acid molecule associated with an activable, single strand-specific endonuclease.

315 strains ofD. pneumoniae were isolated in the Cologne area during the period from October, 1970, to January, 1972. Of these, 274 strains were recovered from cases with respiratory tract infections, and 41 from other pathological material. Predominant serological types were: 19F, 3, 23F, 11A, 8, 9N, 4, 31, 10A and 15F. 55 types were found in the investigated material out of 82 recognized. Antibiotic susceptibility testing revealed high susceptibility to penicillins, cephaloridine, vancomycin, erythromycin and nitrofurans. Single strains resistant to tetracycline, chloramphenicol, lincomycin and novobiocin, were found. There was no relation between antibiotic resistance and serological type. Prevalence of serological types ofD. pneumoniae strains isolated in USA, Denmark, Poland and Germany, was compared.

SUMMARY: R906, a plasmid derived from a wild strain of Bordetella bronchiseptica, was transferred to Escherichia coli k12. In this host it is stably heritable, replicating as a DNA molecule with a molecular weight of 34.6 megadaltons. There are approximately three copies of the plasmid per chromosome. It is a member of compatibility group P. In E. coli, 906 confers resistance to ampicillin, streptomycin, sulphonamides and mercury salts. Resistance to ampicillin is determined by an oxacillin-hydrolysing β-lactamase whereas the resistance to streptomycin is not determined by either of the previously described streptomycin-inactivating enzymes but by some other mechanism.

THE frequency of methicillin resistant Staphylococcus aureus isolated from pathological material from eight Dublin hospitals between April, 1971 and April, 1972 was 5.4 per cent. This frequency justifies their routine detection.

The enzymatic and molecular properties of 14 oxacillin-hydrolyzing β-lactamases, all of them R-factor-specified, were studied, and two distinct groups were found. Four of the enzymes had a molecular weight of 24,000, were active against methicillin, and had an electrophoretic mobility of −0.1 cm/h. Eight enzymes had a molecular weight of 45,000, low activity against methicillin, and an electrophoretic mobility of +0.5 cm/h. The remaining two enzymes were similar to those of the second group in being relatively inactive against methicillin, but their molecular weight was lower (42,000) and their electrophoretic mobility was different (−0.1 cm/h). All the enzymes of both groups were sensitive to inhibition by sodium chloride. The two groups were not completely homogeneous in their enzymatic properties; seven possible subtypes could be recognized.

Genes carried by Eco RI endonuclease-generated fragments of Staphylococcus plasmid DNA have been covalently joined to the E. coli antibiotic-resistance plasmid pSC101, and the resulting hybrid molecules have been introduced into E. coli by transformation. The newly constructed plasmids replicate as biologically functional units in E. coli , and express genetic information carried by both of the parent DNA molecules. In addition, electron microscope heteroduplex analysis of the recombinant plasmids indicate that they contain DNA sequences derived from E. coli and Staphylococcus aureus . Recombinant molecules can transform other E. coli cells for penicillin-resistance markers originally carried by the staphylococcal plasmid, and can be transferred among E. coli strains by conjugally proficient transfer plasmids.

SUMMARY The therapeutic effect of methicillin on skin lesions in guinea-pigs produced by two strains of Staphylococcus aureus showing heterogeneous resistance to methicillin, and by two strains of normal sensitivity, was compared. Methicillin was given intravenously immediately after the intradermal inoculation of staphylococci and the skin lesions were measured 24 hours later. The serum concentrations of methicillin were comparable to those obtained in man with standard dosage and were below or similar to the MIC of the “resistant” staphylococci when this was determined at 37°C. No difference was found after methicillin administration in the size of lesions produced by “resistant” and “sensitive” staphylococci.

The DNA of the thermosensitive R factor, Rts1, has been examined by the technique of sedimentation in alkaline sucrose density gradients. Rts1 DNA was found as closed covalent circles in only a few copies per cell in an Escherichia coli host at the permissive temperature. Rts1 DNA appears to be synthesized at the nonpermissive temperature, but was not found as closed covalent circles. However, circular DNA could be recovered upon shift down to the permissive temperature. The large number of plasmid-negative cells which accumulate after prolonged culture at non-permissive temperature may be due to a strong selective pressure favoring the growth of rare R - segregants.

A membrane fraction from Pseudomonas aeruginosa KM 338 was shown to catalyze in vitro peptidoglycan synthesis from uridine 5′-diphosphate- N -acetylmuramyl- l -alanyl- d - glutamyl-meso-diaminopimelyl- d -alanyl- d -alanine and uridine 5′-diphosphate- N -acetylglucosamine. Synthesized peptidoglycan was partially cross-linked by transpeptidation, which was accompanied by the release of d -alanine. This reaction was strongly inhibited by 25 and 50 μg of penicillin G and carbenicillin per ml respectively, whereas the intact cells were relatively resistant to penicillins (minimal inhibitory concentration of penicillin G and carbenicillin, 30 and 0.125 mg/ml, respectively). Soluble d -alanine carboxypeptidase present in P. aeruginosa KM 338 was studied as well, which was found almost completely inhibited by penicillin G and carbenicillin (10 μg/ml).

Strains of Escherichia coli were constructed that harboured 1, 2 or 3 independent R factors, and their antibiotic resistance levels determined by a spot-testing technique on solid m

Six of seven hfl mutations of Escherichia coli K12, characterized by high frequencies of lysogenization by phage lambda and λcIII mutants, are shown to be tightly linked to, but not within, the purA locus. All six hfl mutations are recessive to wild type in hfl+/hfl merodiploids and all lie in a single complementation group, located just counterclockwise from the purA locus. All six mutations confer a slightly increased resistance to penicillin and rifamycin and a slightly increased sensitivity to sodium dodecyl sulfate. Some cases of intragenic complementation and intragenic recombination were observed. It is argued that the hfl+ gene determines the synthesis of a protein which antagonizes lysogenization by phage lambda. It is further argued that the function of the λcIII gene product is to negate the antagonistic effect of this hfl+ protein.

Escherichia coli (ATCC 12407), generating in the logarithmic growth phase, was killed by penicillin, kanamycin, and rifampin. The logarithm of number of viables of the drug-treated culture decreased linearly with time after a certain lag period and above a minimum drug concentration. The slopes of these plots were characteristic of kill rate constants and were linearly dependent on drug concentrations. The microorganisms developed resistance against the cidal action of the antibiotics. The lower the penicillin concentration and the rate of kill, the greater is the number of resistant organisms, most probably formed by generation in the presence of penicillin. Penicillin was inactivated with time in the culture of organisms, and the resistant individuals eventually grew and were shown to be insensitive to penicillin. When organisms were exposed to the cidal action of kanamycin or rifampin, the appearance of resistant individuals was ascertained. Penicillin yielded debris and ghost cells of E. coli. No such apparent lysis was observed with kanamycin or rifampin. The activity of kanamycin increased with the pH of the medium, so activity can be assigned to the uncharged or lesser charged fraction of the drug concentration. The addition of penicillin or kanamycin to the organisms treated with tetracycline, chloramphenicol, or novobiocin did not show any significant difference in killing rate from organisms not previously treated with such bacteriostatic agents. However, the combination of a bactericidal and a bacteriostatic antibiotic depressed the resistant mutant formation of resistant individuals over that of the bactericidal drug alone. When rifampin was added to organisms pretreated with tetracycline or chloramphenicol, the cidal action of rifampin was significantly reduced.

One hundred sixty-eight strains of nine species of gram-negative bacilli isolated from patients hospitalized at Boston City Hospital in 1972 were tested for susceptibility to amoxicillin, penicillin G, ampicillin, and carbenicillin. The tests were done on heart infusion agar containing twofold dilutions of the antibiotics; a 10-3 dilution of each culture grown overnight in brain heart infusion broth was applied with the replica inoculator. By this method the activity of amoxicillin most resembled that of ampicillin; the former appeared to be slightly more active against strains of Proteus mirabilis and Serratia marcescens and somewhat less active

Two hundred sixty-six strains of Klebsiella pneumoniae isolated from natural water sources in geographically diverse areas (Florida, Massachusetts, and Oregon) were analyzed to determine the serotype, biochemical, virulence, and antimicrobial susceptibility differences between these natural strains and human Klebsiella isolates. Sixty of 72 defined serotypes were found among 210 typable strains. Geographic patterns were present, but in general were not pronounced among serotypes. Reactions with 28 biochemical tests showed percentage responses which were very similar to the summaries of primarily human Klebsiella isolates (as reported by Edwards and Ewing, 1972) and that represented diverse geographic sampling. Virulence studies in representative strains showed no geographic variability and little difference from comparable hospital patient-obtained isolates. In contrast to human hospital isolates, strains demonstrated 90% or greater susceptibility to all antibiotics except ampicillin and carbenicillin; and in further contrast, there was little multiple antibiotic resistance beyond that with ampicillin and carbenicillin.

Results of three quality control trials of antibiotic sensitivity testing carried out on staphylococci by the Birmingham Regional Bacteriologists Group are presented. An overall reduction in the number of discrepant results from 5·2 to 1·2% when retesting the same organisms was thought to be due largely to the alteration in methods of testing for resistance to neomycin- and penicillinase-resistant antibiotics. Improvements were noted in the performance of all laboratories, which were felt to be due partly to participation in the trials.

SUMMARY: A number of R factors have been shown to determine resistance to fusidic acid, an antibiotic effective against Gram-positive bacteria. Among several R factors examined for this property only one was fi−; the remainder were fi+ and of the FII compatibility group.

In cultures of Proteus mirabilis the level of R-factor-TEM-mediated β-lactamase activity rose during the logarithmic phase, reached a maximum value at the end of this phase and fell rapidly when the cells entered the stationary phase. Supernatants from cultures in the stationary phase were found to inhibit R-TEM β-lactamase activity both in cell-free preparations and in intact cells. The inhibitory activity may be due to a proteolytic enzyme excreted into the medium.

The prevalence of Klebsiella species was determined in 25 adults from each of four sections in the Minneapolis-St. Paul area, 100 doctors, nurses, and laboratory technologists from the University of Minnesota Hospitals, 100 patients newly admitted to the hospital, and 100 patients who had been in the hospital longer than 15 days. Klebsiella was isolated from 37%, 30%, 33%, and 43% of these populations, respectively. All but one of the isolates from individuals not associated with hospitals were resistant to only ampicillin and carbenicillin, whereas 18% of strains isolated from patients who had been in the hospital more than 15 days were resistant to several drugs. R-factors were present in resistant bacteria. Fiftyone of 72 possible serotypes of Klebsiella were found, but no types were predominant in any group. Results of biochemical tests were comparable to the results reported by other workers, except that one-third of the Klebsiella organisms isolated were indole-positive.

Streptomyces lipmanii produces two β-lactam antibiotics, penicillin N and 7-(5-carboxyvaleramido)-7-methoxycephalosporanic acid. A method has been developed whereby mutation can be directed toward preselected markers, including some affecting antibiotic production. DNA synthesis was synchronized by amino acid starvation of a leucine auxotroph (LA 473). Double-isotope techniques using [14C]- and [3H]-thymidine provided a means of monitoring DNA synthesis. Aliquots of the synchronized culture were treated with N-methyl-N′-nitro-N-nitrosoguanidine (NTG) and plated on selective media. Mutation frequencies for each marker varied as much as 100-fold. The data were consistent with the hypothesis that NTG preferentially mutates the replicating region of DNA.

GONORRHEA remains the world's most commonly reported communicable disease; there are approximately 100 million new cases per year. 1 In the United States there are one million reported and an estimated two million unreported cases of gonorrhea yearly. 2 The majority of mass-screening studies are performed on patients attending public health or adult ambulatory Care facilities, leading to the widespread and erroneous notion that gonorrhea is exclusiveiy a disease of the poor and the adult. 3-6 Penicillin therapy probably accounts for the declZeaSe in repoi'ted cases which followed the post -World War II peak (Fig: 1).7 A steady increase since 1963, particularly in adolescents (Fig. 2), has occurred. 8 A number of explanations are offe/'ed for the increased incidence of gonorrhea: the observation that some strains of the gonococcus have become resistant to peniciiiin is the most popular among them. The resistance that has de

A screening procedure was used to isolate a number of mutants of Escherichia coli K-12 with low penicillinase activity. By co-transduction with purA , three of the mutants were found to map near 82 min. Penicillinase was purified from one mutant and from a transductant with a temperature-sensitive enzyme. Comparison with wild-type penicillinase revealed similarities in the Ouchterlony immunodiffusion test but differences in the catalytic properties. It is concluded that the mutations have occurred in the structural gene of the chromosomal penicillinase (designated ampC ). Purified enzyme and a temperature-sensitive mutant were used to investigate whether the penicillinase has a physiological function related to biosynthesis or breakdown of murein. No positive evidence for any such function was obtained.

SUMMARY One-hundred and one samples from a wide variety of sewers and water-drainage channels in Bristol, including some sewers that separately drained hospital and domestic premises, were examined for antibiotic-resistant coliform bacilli and for R factors. The antibiotic-sensitivity patterns of over 3000 coliform bacilli isolated were obtained and 1000 resistant strains were tested for R-factor transfer. Hospital sewage contained more coliform bacilli with much higher proportions of resistant bacteria, more R factors, and a greater proportion of R factors carrying multiple resistance, than sewage from domestic and other sources. Despite these findings, it was calculated that less than 5% of the R factors in the sewage output of the City of Bristol originate in hospitals. The normal, healthy population appears to be by far the greatest reservoir of R factors in the community.

The interaction between benzylpenicillin and the specific bacterial cell wall receptor(s) is influenced in a noncontinuous manner through the antibiotic irradiation with λ = 546 nm. The growth of two B. subtilis strains, one sensitive and the other resistant to penicillin, presents a different response pattern to the irradiated antibiotic. For both strains, the inhibitory activity of the antibiotic is increased for 5, 25 and 45 sec penicillin irradiation times. For the resistant strain, the inhibitory activity of the antibiotic is decreased for 15, 35 and 55 sec penicillin irradiation times. This decrease is correlated with the enhancements induced in penicillinase activity, which appear also for 15, 35 and 55 sec of benzylpenicillin irradiation times.

Pseudomonas aeruginosa produces a low basal level of β-lactamase (0.002 to 0.004 IU/mg of protein when benzylpenicillin is used as substrate). The β-lactamase specific activity can be increased several hundredfold by growing the bacteria in the presence of β-lactam antibiotics. This induction was studied in Pseudomonas aeruginosa 1822s. The single-cell resistance to benzylpenicillin was 750 μg/ml. In liquid culture all concentrations of benzylpenicillin tested (25 to 2,000 μg/ml) affected the bacteria similarly: β-lactamase formation was induced, the cells became cholate sensitive, growth rate decreased, filaments were formed, and β-lactamase was excreted. The effect appeared earlier the higher the concentration of the antibiotic. Most of the effects obtained are concerned with the functioning of the outer membrane. The excretion of β-lactamase seems to be due to an opening of the periplasmic volume rather than to lysis of the cells. Carbenicillin gave the same effects as benzylpenicillin at the same concentrations; the 10-fold lower resistance to carbenicillin than to benzylpenicillin can be explained by the inability of the inducible β-lactamase to hydrolyze carbenicillin. The induced β-lactamase was first cell bound and to a great extent located in the periplasmic volume, but later it was excreted into the medium. This extracellular activity was responsible for the detoxification of the medium. This is analogous to the behavior of gram-positive bacteria rather than to that of Enterobacteriaceae .

SUMMARY The survival of ‘marked’ strains of Escherichia coli bearing antibiotic-resistance-transfer (R) factors was studied in the faeces of healthy human volunteers for 7 days after ingestion. Two R factors, determining resistance to ampicillin/chloramphenicol/kanamycin/streptomycin/sulphonamides and to chloramphenicol/streptomycin/sulphonamides/tetracyclines were used in 14 experiments on 12 persons. Strains without R factors served as controls. Both R-factor-bearing and R-factor-free strains were identified by chromosomally determined resistance markers. The R-factor-bearing organisms were isolated from the faeces in fewer numbers than the controls in 52 out of the 54 samples studied. In the two samples in which the reverse phenomenon was observed the effect was not marked. The fall in the number of R-factor-bearing organisms was generally progressive, and 4 days after ingestion the mean faecal population of R-factor-bearing organisms was only 0·5% of the control organisms. The relative decline in the R-factor population probably resulted from impaired vitality of organisms bearing these plasmids rather than from loss of R factors from the cell.

Summary In the studies described in the preceding paper, circumstantial evidence was found for transfer of antibiotic resistance from an ingested strain of Escherichia coli carrying an R factor, R-1, which determined resistance to ampicillin (A), chloramphenicol (C), kanamycin (K), streptomycin (S) and sulphonamide (Su). Resistant organisms isolated from the faeces of a single individual were examined in detail to prove conclusively that the DNA of the ingested plasmid had transferred to other organisms. The O antigens of the resistant faecal isolates were the same as those of two organisms present before the beginning of the experiment, and these strains were resistant to all the determinants of R-1. The levels of resistance of the isolates to these antibiotics were quantitatively consistent with transfer of the plasmid R-1; and the β-lactamase conferring ampicillin resistance was of the same antigenic type. The predominant resistant organism isolated from the faeces transferred resistance to ACKSSu to laboratory recipients, and plasmid DNA isolated from such strains had the same molecular weight as R-1 and gave 100 per cent. DNA hybridisation with DNA from R-1. Small populations of another strain were also isolated which transferred resistance to ACKSSu and to tetracycline, and this plasmid contained all of the DNA base sequence of R-1 plus additional DNA. The serotype of this strain was the same as that of a strain already resistant to tetracycline before the beginning of the experiment. These results prove that R-factor transfer must have occurred during or after antibiotic therapy and illustrates possible dangers of chemotherapy.

The ampicillin resistance of clinical isolates of Shigella sonnei is due to β-lactamase production. Two kinds of resistance are found: low level, nontransmissible; and high level, tranmissible. The nontransmissible type of resistance results from a chromosomal mutation which increases the production of a β-lactamase that hydrolyses cephalosporins relatively rapidly and gives cephalothin resistance. The transmissible type of resistance is due to an R factor mediating the synthesis of a different β-lactamase that does not significantly hydrolyze cephalosporins or confer cephalothin resistance. One clinical isolate is shown to possess simultaneously both these mechanisms of ampicillin resistance.

The ampicillin resistance (β-lactamase) determinant of RP4 can be transposed onto various other replicons genetically unrelated to RP4 including several but not all R factors.

Four different mutants of Escherichia coli were isolated after selection for an increased tolerance to glycine (3 to 4%). The mutants showed additional effects, notably an increased sensitivity to penicillin G. The interpretation is that permeability to several agents is changed as a result of some distorted function in the cell envelope. Reversion analysis showed that the complex change in phenotype is the result of a single point mutation. The four mutants represent four previously undescribed genes termed qme, of which qmeC could be genetically located between aroB and str, qmeD near to lys and thy in the order qmeD-lys-thy, qmeE near aroD, and qmeF in the 17/22 min region.

Sixty-four ampicillin-resistant strains of Escherichia coli were studied. Six characters were examined: (i) resistance to ampicillin, cephalothin, and carbenicillin, (ii) synergy between ampicillin and cloxacillin, (iii) level of β-lactamase activity after osmotic shock, (iv) transferability of ampicillin resistance, (v) immunological characterization of the enzyme, and (vi) determination of substrate profiles. One class of strains was found in which synthesis of β-lactamase is inferred to be plasmid mediated; these strains are highly resistant to ampicillin and carbenicillin, sensitive to cephalothin, do not show synergism between ampicillin and cloxacillin, and reveal a high enzymatic activity after osmotic shock. A second class is formed by strains for which β-lactamase synthesis is inferred to be chromosomal; these strains present a low resistance level to ampicillin, are sensitive to carbenicillin and resistant to cephalothin, show a synergism between ampicillin and cloxacillin, and reveal a very low enzymatic activity after osmotic shock. These characters may be used to differentiate periplasmic and cell-bound β-lactamases.

SUMMARY A total of 880 samples of faeces from 584 neonates in four hospitals were examined for the presence of antibiotic-resistant Gram-negative bacilli. The proportion of strains of Escherichia coli and Klebsiella spp. carrying R factors was also determined. Some resistant strains of E. coli and Klebsiella spp. were rapidly acquired after birth and the number of isolates increased in relation to the length of hospital stay. The proportion of isolates of Klebsiella spp. increased to over 60% in babies in special care units but increased to a lesser extent (less than 30%) in other wards. The four hospitals showed differences in the proportion of babies carrying antibiotic-resistant strains and this was partly attributable to the inclusion of samples from special care units in three of the hospitals. Antibiotic-resistant Gram-negative bacilli other than E. coli and Klebsiella spp. were isolated much less frequently. Transferable resistance was demonstrated in 49% of 208 resistant strains of E. coli and in only 6·5% of 240 strains of Klebsiella spp. An increased frequency of resistant strains was found in babies associated with abnormal deliveries and in babies treated with antibiotics. Resistant strains were probably acquired initially from the mothers, but although there was evidence of cross-infection with E. coli and Klebsiella spp. particularly in special care units, no common source was identified.

Summary The frequency of antibiotic resistance in coliform bacilli causing asymptomatic bacteriuria of pregnancy in two hospitals in West London was studied. Approximately one-fifth of the strains were resistant to at least one antibiotic. No increase in resistance was shown when these figures were compared with a previous study of symptomatic bacteriuria made in 1968–69, although both studies show an increase compared with figures obtained in 1962–63. In one-third of strains, resistance was shown to be mediated by R factors.

SUMMARY: We tested 151 strains representing the genera Nocardia and Gordona, the taxon ‘Mycobacterium’ rhodochrous and a collection of strains isolated from bagasse for their in vitro susceptibility to 52 antimicrobial agents by using the impregnated filter-paper disc method. The ‘bagasse’ isolates were resistant to most of the antimicrobial agents but the nocardiae, gordonae and rhodochrous groups formed a series with increasing sensitivity. The nocardiae were inhibited by low concentrations of a number of antibiotics, notably erythromycin, miconazole, gentamycin and tobramycin, which may be of value in treating Nocardia infections. Certain antibiotics, at suitable concentrations, provided data of value for the classification and identification of nocardioform bacteria.

Bacterial endocarditis remains a serious complication of Staphylococcus aureus (coagulase positive) bacteremia. However, it occurs significantly less frequently in those who become bacteremic in hospital, in comparison to those whose infection is community-acquired. This difference appears related to a longer bacteremic period, prior to therapy, in those with community-acquired disease. Since a significant percentage of strains of Staphylococcus aureus are still resistent to penicillin, initial treatment should include a penicillinase resistent penicillin or cephalosporin. Those patients without endocarditis appear optimally treated with two to three weeks of appropriate antibiotic therapy.

In 310 patients, divided into groups receiving penicillin and streptomycin, cephalothin, or no antibiotics, culture specimens were taken at four stages of triage, and each patient was followed and observed for infection. A correlation was made between retrieval of bacteria after injury and incidence of infection. In control patients the incidence of infection was 13.9 per cent while in the group receiving penicillin and streptomycin it was 9.7 per cent, the difference not being statistically significant. The group of patients receiving cephalothin had a significantly lower infection rate of 2.3 per cent.

Among men and women with uncomplicated anogenital gonococcal infection, 95 % were cured by a single 3.0-g oral dose of amoxicillin, 91% were cured by 3.0 g of ampicillin, and 98% were cured by 3.5 g of ampicillin given with 1.0 g of probenecid. The distribution of minimal inhibitory concentrations of ampicillin for Neisseria gonorrhoeae was bimodal. Gonococci isolated before treatment were available from 12-16 patients with anogenital infection that persisted despite therapy, and 11 of these 12 isolates were among the more resistant population, having minimal inhibitory concentrations >,0.25 [tg of ampicillin/ml. In contrast, seven (33% ) of 21 oropharyngeal gonococcal infections were not cured by treatment with one of these regimens, and therapeutic failure was not limited to patients harboring the more resistant gonococci. N. gonorrhoeae was recovered from the oropharynx of five additional patients after treatment. Thus, oropharyngeal infection accounted for 12 (43%) of 28 persistent or recurrent infections in this study.

The five-year review reported herein tends to confirm other reports indicating that nosusceptibility patterns can be regarded as permanent, and that susceptibility testing of the isolated pathogens is necessary in each case of resistant urinary tract infection. On the other hand, it appears that the belief in the pattern stability of the chemical urinary agents may not be entirely erroneous. Antibacterial agents such as nitrofurantoin have shown a relatively stable pattern of effectiveness and clinical safety over a number of years. They continue to have an important role in the treatment of nonobstructive urinary tract disease.