The search for alternative therapeutic agents for listeriosis includes the quinolone group. Accordingly, the bactericidal activity of ciprofloxacin, levofloxacin, lomefloxacin, ofloxacin, sparfloxacin, and temofloxacin, in comparison with that of ampicillin and sulfamethoxazole-trimethoprim, was evaluated against Listeria monocytogenes at 24 and 48 h of incubation using time-kill kinetic methodology. The inhibitory concentrations for each agent fell into a narrow range comparable with ampicillin. For example, the minimum inhibitory concentration (MIC) ranges, MIC90 (24 h), and MIC90 (48 h) of the most active quinolone, sparfloxacin, were 0.25–2, 2, and 2 μg/ml, respectively, with 4 μg/ml achieving ⩾99.9% killing of the inoculum at 24 h with no regrowth by 48 h. At 2–4 times the MIC, bactericidal activity for all quinolones tested was noted at 24 h, unlike the action of ampicillin, which only becomes bactericidal at 48 h. These concentrations are within the achievable range of serum concentrations for a number of these agents. Because selected new fluoroquinolones at two to four times the MIC show bactericidal activity at 24 h, these agents may prove useful as therapeutic alternatives for the treatment of listeriosis.

Purpose: To review changes in the medical complications of drug abuse that have occurred since the authors reviewed them 25 years ago. Data Source: Manual search of the internal medicine and subspecialty literature of the past three decades that was selected by the authors. Study Selection: Selected studies were of three typesbaseline studies for the period ending in 1968, studies after 1968 that emphasized changes from baseline, and studies after 1968 that emphasized change (or the absence of change) and the manner in which clinicians conceptualized problems. Data Extraction: We extracted data that showed changes in the diseases, the appearance of new diseases, or the disappearance of formerly common diseases. Results of Data Synthesis: The diseases complicating drug abuse are now more widely disseminated than they were in the last 25 years. Some former diseases of addiction such as tetanus and malaria are now rare. Diseases (such as human immunodeficiency virus infection) not known to exist or rare 25 years ago now occur frequently. The drugs of abuse have also changed; for example, cocaine is now much more common. Conclusions: Treating the acute medical problems (mostly infectious diseases) in poor, undereducated, and often noncompliant intravenous drug users is far more complex than previously described. Although some features have remained constant, the emergence of human immunodeficiency virus infection and changes in patterns of drug use have radically altered patient management.

The in-vitro activity of meropenem, imipenem, piperacillin, cefoxitin, ampicillin/sulbactam, clindamycin and metronidazole was determined against 395 strains of strict and facultative anaerobes, including Gardnerella vaginalis, Lactobacillus spp. and Mobiluncus spp. The activities of meropenem and imipenem were within one dilution of their MIC50 and MIC90 values. One isolate of Bacteroides fragilis, two of Bacteroides distasonis, and two of Bacteroides ovatus showed resistance or diminished susceptibility to meropenem and imipenem. Metronidazole was active against almost all obligate anaerobic isolates. Some non-spore-forming Gram-positive bacilli and lactobacilli were resistant. Ampicillin/sulbactam inhibited almost all isolates at < or = 16/8 mg/L. The activity of clindamycin and cefoxitin was relatively good, but some strains of non-fragilis B. fragilis group species were resistant. Piperacillin was the least active agent tested.

Escherichia coli strains resistant to ampicillin/sulbactam from hospitals in 4 different geographic locations were examined with respect to type and amount of beta-lactamase produced. A total of 5 strains was examined from each region. The isoelectric points of all of the involved beta-lactamases were 5.4, corresponding to TEM-1. Km and Vmax values of the beta-lactamases among the clinical isolates resembled those from the control TEM-1 strain. In an 18-hour broth culture the highly resistant isolates produced 3 times more beta-lactamase as compared to the ampicillin/sulbactam-susceptible isolates. However, the highly resistant strains contained approximately the same amount of plasmid DNA (size of > 6,500 bp) as the susceptible isolates. In transformation experiments, both the resistance and the degree of resistance appeared to have been transferable by plasmids. The mechanism for resistance is likely to be a baseline overproduction of TEM-1 beta-lactamase due to either an alteration in the control of gene expression or simply to an increase in the number of copies of the beta-lactamase gene in the plasmids.

We compared the inoculum effects for 109 recent clinical isolates of the Bacteroides fragilis group of cefoxitin, cefotetan, ceftizoxime, ceftriaxone, and three beta-lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) and their penicillin-derived components. Bactericidal activity was assayed and morphologic changes were monitored for selected strains exhibiting a large inoculum effect. Ceftizoxime demonstrated the largest inoculum effect, followed by cefotetan and ceftriaxone. The large inoculum effect of ceftizoxime and ceftriaxone was correlated with filamentous transformation at the high inoculum (10(8) CFU/ml) and lack of bactericidal activity suggesting drug destruction or inactivation. Cefotetan was bactericidal for B. fragilis isolates but not for other members of the B. fragilis group. Cefoxitin showed the least inoculum effect and was consistently bactericidal at high (10(8) CFU/ml), standard (10(6) CFU/ml), and low (10(4) CFU/ml) inocula, followed by ampicillin-sulbactam. Piperacillin-tazobactam and ticarcillin-clavulanic acid showed an intermediate inoculum effect. The degree of inoculum effect observed generally correlated with bactericidal activity at all inocula.

To reassess the epidemiology and treatment of listeriosis in the United States, we reviewed greater than 120 cases of listeriosis from four medical centers in three geographically separated cities: Los Angeles County-University of Southern California Medical Center (LAC-USCMC); Rush-Presbyterian-St. Luke's Hospital, Chicago; the University of Illinois Hospital, Chicago; and Vanderbilt University Hospital, Nashville, Tennessee. The epidemiological pattern at LAC-USCMC was relatively narrow; more than two-thirds of the cases occurred during the perinatal period. Cases at Vanderbilt University Hospital represented the opposite end of the spectrum; the majority of these occurred in nonpregnant, older adults who had received organ transplants. An intermediate pattern of cases was observed at the two medical centers in Chicago. Potential risk factors included pregnancy, neonatal status, organ transplantation, renal failure, malignancy, systemic lupus erythematosus, steroid therapy, and AIDS (two cases). Antimicrobial agents noted to be effective were, as expected, penicillin and ampicillin; the cephalosporins were ineffective. The mortality associated with listeriosis occurred mainly among premature infants and stillbirths delivered from infected pregnant women and was markedly less among neonates and adults.

Journal Article Quinolones for the Treatment of Infections Due to Salmonella Get access Charles E. Cherubin, Charles E. Cherubin Department of Medicine, Mercy Hospital and Medical Center, Chicago, Illinois; and the Medical Service, Department of Veterans Affairs Medical Center, East Orange, New Jersey Reprints and correspondence: Dr. Charles E. Cherubin, Department of Medicine, Mercy Hospital and Medical Center, Chicago, Illinois 60616. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert H. K. Eng Robert H. K. Eng Department of Medicine, Mercy Hospital and Medical Center, Chicago, Illinois; and the Medical Service, Department of Veterans Affairs Medical Center, East Orange, New Jersey Search for other works by this author on: Oxford Academic PubMed Google Scholar Reviews of Infectious Diseases, Volume 13, Issue 2, March-April 1991, Pages 343–344, https://doi.org/10.1093/clinids/13.2.343 Published: 01 March 1991

In vitro susceptibility testing of Listeria monocytogenes most often reveals both ampicillin and penicillin as inhibitory as opposed to bactericidal with activity comparable to chloramphenicol and tetracycline. Yet, the former two penicillins are more effective for Listeria meningitis than are the latter agents. Accordingly, we reassessed the bactericidal activity of agents used in listeriosis in order to determine in vitro methodology that would be more predictive of clinical outcome. We found that bactericidal activity for > 48 hr by either minimum inhibitory-minimum bactericidal concentration (MIC-MBC) testing or time-kill kinetic studies was the best predictor of clinical efficacy. This correlation may be due to Listeria being a slow-growing microorganism. In addition to ampicillin and penicillin, we found trimethoprim-sulfamethoxazole, vancomycin, and imipenem to exhibit bactericidal activity for 48 hr. For the first two agents, this is in agreement with the results of clinical experience.

We compared the inoculum effects of 105 recent clinical isolates of the family Enterobacteriaceae on cefoxitin, other cephalosporins, aztreonam, and three beta-lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) and their penicillin-derived components. Piperacillin and aztreonam showed the largest inoculum effect, and cefoxitin showed the smallest. The other cephalosporins tested (cefotetan, ceftizoxime, and ceftriaxone) showed an intermediate inoculum effect. In general, the inoculum effect was of greater magnitude for the penicillin and beta-lactamase inhibitor combinations than for the cephalosporins tested. Bactericidal activity was assayed and morphologic changes were monitored for selected strains exhibiting a large inoculum effect. MICs correlated with bactericidal activity at an inoculum level of 10(5) CFU/ml, while activity at 10(8) CFU/ml was variable. Cefoxitin demonstrated the least filamentous transformation and the most rapid bactericidal activity. Aztreonam showed the most marked filamentous transformation and was no longer bactericidal at 10(8) CFU/ml. The beta-lactamase inhibitor combinations showed variable bactericidal activity, and regrowth occurred with a number of strains with all three agents tested.

The antibiotic carry-over effect occurs when antibiotic transferred onto the agar plate with the subcultured aliquot is sufficient to inhibit the growth of viable bacteria, and results in a falsely low MBC. This phenomenon was eliminated by widely streaking the transferred aliquot over at least one half of a 100 mm agar plate or by centrifugation and resuspension of the organisms in non-antibiotic-containing media prior to plating. Both methods require more effort than the current method of MBC determination, but can be performed in clinical laboratories and are thus highly recommended in the testing of organisms from endocarditis and meningitis patients.

Reference strains of Escherichia coli (ampicillin-susceptible and -resistant ATCC strains, and known TEM-1 and TEM-2 beta-lactamase producers) were tested in vitro and in the in-vivo mouse thigh infection model against four beta-lactamase inhibitor compounds (BICs: amoxycillin/clavulanic acid, ampicillin/sulbactam, ticarcillin/clavulanic acid, and piperacillin/tazobactam), selected cephalosporins, and imipenem. The ATCC strains (ampicillin-susceptible and -resistant) were susceptible to the BICs in disc and MIC tests. Three or more logs of killing were observed at the NCCLS breakpoint concentrations. However, the TEM-1 and TEM-2 producers were resistant in disc tests to ampicillin/sulbactam and amoxycillin/clavulanic acid, and showed intermediate susceptibility to ticarcillin/clavulanic acid. MICs were at or near the breakpoint, but bactericidal activity was only noted at the probable breakpoint concentration of piperacillin/tazobactam. Cefoxitin, cefotaxime, cefpirome and imipenem, but not cephalothin, showed greater bactericidal activity and lower MICs for the TEM-producing strains than the BICs. The viable count of the TEM-1 producer was not reduced in the mouse thigh model by ampicillin/sulbactam or amoxycillin/clavulanic acid, but cefpirome and cefotaxime reduced the viable count by approximately three logs. There was a 50% mortality rate in mice receiving the two BICs. The ampicillin-susceptible ATCC strain of E. coli was killed to a similar degree by all agents tested. Overall, the BICs appeared inferior, in both in-vivo and in-vitro tests to selected cephalosporins and imipenem when tested against reference strains of E. coli producing TEM-1 or TEM-2 beta-lactamase. The large inoculum effect and poor bactericidal activity observed with the BICs suggest they could be less effective in certain clinical situations.

The epidemiology of species of the Bacteroides fragilis groups isolated at Los Angeles County-University of Southern California Medical Center was examined. In addition, frequency of resistance to six beta-lactam antibiotics (cefmetazole, cefotetan, ceftizoxime, imipenem, penicillin, and cefoxitin) and to clindamycin, chloramphenicol, and metronidazole was determined for each species. While B. fragilis was most commonly isolated, the other species of the B. fragilis group accounted for half of the isolates. Seven percent of 1,128 patients with infections due to species of the B. fragilis group were bacteremic. A review of bacteremic cases indicated that non-fragilis species were highly pathogenic. Resistance to clindamycin ranged from 8% to 22% among species and was most common among isolates of Bacteroides distasonis and Bacteroides thetaiotaomicron. Significant differences in antimicrobial activity were noted among the agents tested. Only imipenem, chloramphenicol, and metronidazole were predictably effective against non-fragilis species of the B. fragilis group. Prompt identification of species and susceptibility testing of clinical isolates of this group are needed if a newer beta-lactam agent or clindamycin is to be used for initial therapy.

A review of the world literature on the penetration (ratio of concentrations of cerebrospinal fluid to concentrations of serum) and attainable antibiotic concentrations in the cerebrospinal fluid in humans for cefuroxime, cefoxitin, cefotaxime, ceftizoxime, cefmenoxime, cefamandole, cefoperazone, moxalactam, ceftazidime, and ceftriaxone indicates that, with the exceptions of cefamandole and cefoperazone, all agents appear equivalent. We conclude that the choice of cephalosporin for the treatment of acute bacterial meningitis should depend mainly on the potency of the agent for the specific meningeal pathogens in question. For the treatment of common meningeal pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis) and for gram-negative bacilli, mainly Escherichia coli and Klebsiella (excluding Pseudomonas aeruginosa), the cefotaxime-ceftriaxone group of cephalosporins has accrued the most clinical experience and the most pharmacokinetic data, while for P. aeruginosa the major interest has centered on ceftazidime.

Journal Article A Critique of Semiautomated Susceptibility Systems Get access Charles E. Cherubin, Charles E. Cherubin Please address requests for reprints to Dr. Charles E. Cherubin, Department of Medicine, Bayley Seton Hospital, Bay Street and Vanderbilt Avenue, Staten Island, New York 10304. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert Eng, Robert Eng Search for other works by this author on: Oxford Academic PubMed Google Scholar Maria Appleman Maria Appleman Search for other works by this author on: Oxford Academic PubMed Google Scholar Reviews of Infectious Diseases, Volume 9, Issue 3, May 1987, Pages 655–659, https://doi.org/10.1093/clinids/9.3.655 Published: 01 May 1987 Article history Received: 07 August 1986 Published: 01 May 1987

The new cephalosporins should be explored for Salmonella septicemia efficacy, because of multiple-drug resistance, the high incidence of patient allergies to ampicillin and sulfamethoxazole-trimethoprim, and the limited number of antibiotics with proven efficacy. This study reports on six widely used cephalosporins: cephalothin, cefamandole, cefoperazone, cefoxitin, cefotaxime, and ceftriaxone with respect to in vitro killing of Salmonella. This in vitro activity was related to the stability of the agents to beta-lactamases. Cefoperazone was the least stable, followed by cefamandole and cephalothin. Cefoxitin, cefotaxime, and ceftriaxone were the most stable. The beta-lactamase-unstable agents permitted regrowth of beta-lactamase-producing salmonella within 36 hours. Standard susceptibility tests showed good inhibitory levels by these unstable agents at 18 hours, but the minimum inhibitory concentrations increased dramatically with longer incubation periods. Based on these results, past cephalothin failures for ampicillin-resistant Salmonella can be explained. Additionally, there should be a dichotomy of effectiveness in the new cephalosporins depending on their beta-lactamase stability. The stable cephalosporins deserve further clinical trials in the treatment of beta-lactamase-producing Salmonella infections.

The frequency with which resistant variants could be found in Pseudomonas aeruginosa ATCC 27853 during growth in media with and without antibiotics was determined for ticarcillin, piperacillin, cefotaxime, latamoxef, cefoperazone, ceftriaxone, ceftazidime, aztreonam and imipenem. The resistance frequency was highest for ceftriaxone, cefotaxime, cefoperazone and piperacillin (up to 2 X 10(-4)) and lowest for ticarcillin, latamoxef, ceftazidime, aztreonam and imipenem (less than 10(-8)). The resistant variants showed cross-resistance to all of the beta-lactam antibiotics tested with the exception of imipenem. The MIC profiles of all variants were similar regardless of which antibiotic the cultures had been exposed to previously. Although all resistant variants produced and excreted cephalosporinases, increased resistance was demonstrated to both cephalosporinase-susceptible and cephalosporinase-stable beta-lactam antibiotics.