Failure of Ciprofloxacin to Eradicate Convalescent Fecal Excretion after Acute Salmonellosis: Experience during an Outbreak in Health Care Workers

Neill, Marguerite A.; Opal, Steven M.; Heelan, Judith S.; Giusti, Ruthann M.; Cassidy, Jane Ellen; White, R F; Mayer, Kenneth H.

doi:10.7326/0003-4819-114-3-195

Cited by 127 publications

(40 citation statements)

References 20 publications

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“…Unfortunately, this limited our ability to define the true duration of colonization and perhaps also the magnitude of the immune responses had they been allowed to clear the organism independently. Clinically, administration of antibiotics has been associated in some studies with prolonged duration of positive stool cultures or even symptomatic relapse in subjects with nontyphoidal Salmonella gastroenteritis (2,24,25). This was not observed in our study, perhaps in part because a 3-day course of an antibiotic with little effect on the anaerobic intestinal flora was used.…”

Section: Discussionmentioning

confidence: 99%

Pilot Study of phoP/phoQ -Deleted Salmonella enterica Serovar Typhimurium Expressing Helicobacter pylori Urease in Adult Volunteers

2000

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Attenuated Salmonella enterica serovar Typhi has been studied as an oral vaccine vector. Despite success with attenuated S. enterica serovar Typhimurium vectors in animals, early clinical trials of S. enterica serovar Typhi expressing heterologous antigens have shown that few subjects have detectable immune responses to vectored antigens. A previous clinical study of phoP/phoQ-deleted S. enterica serovar Typhi expressing Helicobacter pylori urease from a multicopy plasmid showed that none of eight subjects had detectable immune responses to the vectored antigen. In an attempt to further define the variables important for engendering immune responses to vectored antigens in humans, six volunteers were inoculated with 5 ؋ 10 7 to 8 ؋ 10 7 CFU of phoP/phoQdeleted S. enterica serovar Typhimurium expressing the same antigen. Two of the six volunteers had fever; none had diarrhea, bacteremia, or other serious side effects. The volunteers were more durably colonized than in previous studies of phoP/phoQ-deleted S. enterica serovar Typhi. Five of the six volunteers seroconverted to S. enterica serovar Typhimurium antigens and had strong evidence of anti-Salmonella mucosal immune responses by enzyme-linked immunospot studies. Three of six (three of five who seroconverted to Salmonella) had immune responses in the most sensitive assay of urease-specific immunoglobulin production by blood mononuclear cells in vitro. One of these had a fourfold or greater increase in end-point immunoglobulin titer in serum versus urease. Attenuated S. enterica serovar Typhimurium appears to be more effective than S. enterica serovar Typhi for engendering immune responses to urease. Data suggest that this may be related to a greater stability of antigen-expressing plasmid in S. enterica serovar Typhimurium and/or prolonged intestinal colonization. Specific factors unique to nontyphoidal salmonellae may also be important for stimulation of the gastrointestinal immune system. Attenuated salmonellae have been extensively studied as live bacterial vectors for delivery of heterologous antigens because these intracellular microorganisms stimulate humoral, mucosal, and cellular immune responses in humans and animals. A goal of these studies has been to develop multivalent oral vaccines based upon Salmonella enterica serovar Typhi for human use. The existence of the safe live attenuated vaccine strain Ty21a, an effective vaccine against typhoid fever, and the species specificity of S. enterica serovar Typhi for humans has focused investigative attention on this serotype. Most human studies of attenuated S. enterica serovar Typhi have been based on preclinical data obtained in the murine model of systemic salmonellosis in which BALB/c mice are infected orally with attenuated Salmonella enterica serovar Typhimurium. More recently, mice have been infected nasally with S. enterica serovar Typhi strains (8). Although murine experiments are useful screening studies, their predictive value in forecasting immunogenicity and safety in clinical trials of atte...

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Section: Discussionmentioning

confidence: 99%

Pilot Study of phoP/phoQ -Deleted Salmonella enterica Serovar Typhimurium Expressing Helicobacter pylori Urease in Adult Volunteers

2000

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“…almonella gastroenteritis is normally a self-limiting disease, and antimicrobial therapy is not generally recommended (1,2). However, antimicrobial therapy is indicated for the management of severe diarrhea or extraintestinal infection caused by Salmonella spp.…”

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confidence: 99%

Performance of Etest and Disk Diffusion for Detection of Ciprofloxacin and Levofloxacin Resistance in Salmonella enterica

et al. 2015

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dWe compared Etest and disk diffusion to broth microdilution for the detection of fluoroquinolone resistance in 135 typhoidal and nontyphoidal serovars of Salmonella. Categorical agreements for the ciprofloxacin and levofloxacin Etests were 89.6 and 83.7%, respectively. Disk diffusion categorical agreements were 88.2 and 93.3%, respectively. Only minor errors were observed. S almonella gastroenteritis is normally a self-limiting disease, and antimicrobial therapy is not generally recommended (1, 2). However, antimicrobial therapy is indicated for the management of severe diarrhea or extraintestinal infection caused by Salmonella spp. and for the treatment of enteric fever, which is caused by Salmonella enterica serovars Typhi and Paratyphi A, B, and C. The fluoroquinolones ciprofloxacin and levofloxacin are important agents for the treatment of these infections (3). Fluoroquinolone resistance in Salmonella is a significant clinical concern, particularly among typhoid serovars of Salmonella isolated in Asia. The most common fluoroquinolone resistance mechanism among these isolates is mutation to the quinolone resistance-determining region (QRDR) of the topoisomerase gene gyrA, resulting in elevated ciprofloxacin and levofloxacin MICs (0.12 to 0.5 g/ml) and full resistance to the quinolone nalidixic acid (MIC, Ն32 g/ml) (4). Patients infected with such isolates have delayed responses to fluoroquinolone therapy and, in many cases, clinical failures (4). As such, the Clinical and Laboratory Standards Institute (CLSI) has historically instructed laboratories to perform a nalidixic acid disk diffusion or MIC test in order to screen for this resistance mechanism among Salmonella isolates for which susceptibility testing was warranted (4). However, fluoroquinolone resistance in Salmonella can also be attributed to mutation to the QRDR of other topoisomerase genes (gyrB, parC/E) or by the acquisition of plasmid-mediated quinolone resistance determinants, such as the qnr and aac(6=)-Ib-cr genes. In contrast to QRDR topoisomerase mutations, isolates with fluoroquinolone resistance associated with plasmid-mediated mechanisms are not necessarily resistant to nalidixic acid (5).In 2013, the CLSI revised the ciprofloxacin, levofloxacin, and ofloxacin MIC interpretive criteria (breakpoints) for Salmonella and the disk diffusion breakpoints for ciprofloxacin, in part to better detect these fluoroquinolone resistance mechanisms in Salmonella spp. (Table 1) (6). At present, no levofloxacin or ofloxacin disk diffusion breakpoints for Salmonella have been established by the CLSI. The U.S. Food and Drug Administration (FDA) has accordingly revised the ciprofloxacin MIC interpretive criteria for S. enterica serovar Typhi but not for other Salmonella serovars or for levofloxacin or ofloxacin. Furthermore, no commercial MIC susceptibility test panels produced in the United States contain fluoroquinolone concentrations low enough to allow use of the current CLSI breakpoints. Thus, laboratories in the United States have the option of perf...

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“…As noted above, apart from the report of one child who had a relapsed Campylobacter jejuni infection after a course of erythromycin, there have been no reports of recrudescent C. jejuni infections in healthy adults following a course of strainsensitive antibiotics (34). An asymptomatic recrudescent infection after antibiotic therapy that is not explained by acquired resistance or biliary disease is well described for acute nontyphoidal salmonellosis (Salmonella java) (33).…”

Section: Discussionmentioning

confidence: 99%

Recrudescent Campylobacter jejuni Infection in an Immunocompetent Adult following Experimental Infection with a Well-Characterized Organism

Baqar

Tribble

Carmolli

et al. 2010

Clin Vaccine Immunol

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The recrudescence of infection with Campylobacter jejuni after appropriate antibiotic treatment has not been previously reported in an immunocompetent adult. We present the complete clinical, microbiologic, and immunologic evaluation of a closely monitored healthy male with recrudescent C. jejuni infection occurring in the absence of immunodeficiency following experimental infection with a well-characterized strain. After antibiotic treatment, the initial infection was clinically cleared and microbiologically undetectable. Subsequently, two episodes of recrudescence occurred, with no change in in vitro antibiotic sensitivity being detected. The immune responses of the individual were compared to those of other participants in the experimental infection study: innate immune responses, including fecal cytokines and C-reactive protein, were intact; however, measures of Campylobacter-specific adaptive immune responses were absent, including serum antibodies, antibody-secreting cells, and in vitro gamma interferon responses. No primary or secondary immunodeficiency was identified. Recrudescent Campylobacter infections after treatment may be more common than has previously been appreciated. This work adds to our understanding of the human immune response to natural Campylobacter infection and reiterates the importance of pathogen-specific adaptive immune responses to this globally important pathogen.

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Failure of Ciprofloxacin to Eradicate Convalescent Fecal Excretion after Acute Salmonellosis: Experience during an Outbreak in Health Care Workers

Cited by 127 publications

References 20 publications

Pilot Study of phoP/phoQ -Deleted Salmonella enterica Serovar Typhimurium Expressing Helicobacter pylori Urease in Adult Volunteers

Pilot Study of phoP/phoQ -Deleted Salmonella enterica Serovar Typhimurium Expressing Helicobacter pylori Urease in Adult Volunteers

Performance of Etest and Disk Diffusion for Detection of Ciprofloxacin and Levofloxacin Resistance in Salmonella enterica

Recrudescent Campylobacter jejuni Infection in an Immunocompetent Adult following Experimental Infection with a Well-Characterized Organism

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