Pivmecillinam is an orally active prodrug of mecillinam, an extended-spectrum penicillin antibiotic. Pivmecillinam is the pivaloyloxymethyl ester of mecillinam. Mecillinam is a 6-b-amidinopenicillanic acid [1-2] and in its hydrochloride dihydrate form, is suitable for i.m. or i.v. administration, but it is not absorbed when given orally. Pivmecillinam is only considered to be active against Gram-negative bacteria, and is used primarily in the treatment of lower urinary tract infections [3-4]. It has also been used to treat paratyphoid fever .
Mecillinam is active against most pathogenic Gram-negative bacteria, except Pseudomonas aeruginosa and some species of Proteus . Several studies have also found it to be as effective as other antibiotics for treating Staphylococcus saprophyticus infection, even though it is Gram-positive, possibly because mecillinam reaches very high concentrations in urine .
Urinary tract infections
Mecillinam has been fairly extensively used for the treatment of urinary tract infections (UTIs). Escherichia coli infections respond very well and those caused by other Enterobacteriaceae, such as Klebsiella, Proteus, or Enterobacter spp., also usually respond satisfactorily [7-8]. The efﬁcacy of mecillinam in both uncomplicated and complicated infections is similar to that of ampicillin or co-trimoxazole [8-10]. Bacteriologic success rate in patients with bacteriuria in pregnancy was 87% in one study, and the drug appeared safe as there were no drug-related fetal abnormalities . Pivmecillinam was compared with pivampicillin in gynecologic patients with bacteriuria at the time of removal of an indwelling catheter 3–4 days after surgery. After treatment, all 17 patients in the pivmecillinam group, but only 6 of 14 patients in the pivampicillin group were cured . Uncomplicated urinary tract infections caused by S. saprophyticus may occasionally respond to pivmecillinam treatment, but the drug is unlikely to be effective in infections caused by E. faecalis . However, other authors who treated 15 women with S. saprophyticus bacteriuria, found on review 2–4 weeks after treatment, that only 11 patients were cured . They suggested that mecillinam should not be used for treatment of urinary tract infections caused by this organism, which is resistant to mecillinam in vitro. Pivmecillinam or a pivmecillinam–pivampicillin combination have been compared for the treatment of urinary tract infections in patients with underlying urological abnormalities. Combination therapy was more successful in eradicating urinary pathogens [15-17]. Combination mecillinam and cefoxitin therapy was efﬁcacious for the treatment of complicated urinary tract infections caused by multi-resistant Serratia marcescens strains . Pivmecillinam in a single bed-time dose of 5–10 mg/kg appeared satisfactory for long term prophylaxis to girls with recurrent bacteriuria . The markedly enhanced effect obtained when E. coli is exposed to mecillinam in conditions of low osmolality, suggests that it may be advisable to reduce urine osmolality by increased ﬂuid intake, when mecillinam is used to treat urinary tract infections .
In a study, 26 patients with typhoid or paratyphoid fever; cure was obtained in 23 and the three others relapsed . Results in 21 other patients treated with co-trimoxazole did not differ from the mecillinam-treated group, except in the frequency of convalescent excretion of salmonellae. Only three patients in the mecillinam-treated group had negative stools following treatment, compared with 13 out of 21 in the co-trimoxazole-treated group. Another study had less favorable results with only 7 of 12 typhoid fever patients being cured by mecillinam . Two other patients with typhoid fever who were cured clinically by chloramphenicol, but had positive stool cultures after therapy, were given pivmecillinam 800 mg three times per day in an attempt to eradicate the organisms. Unexpectedly, while the patients were taking the drug, they had clinical relapses of the disease, conﬁrmed by positive blood cultures  (Jones et al., 1982). These experiences suggest that mecillinam alone is unreliable for the treatment of typhoid fever. Mecillinam 800 mg was used with amoxicilin 750 mg, both given i.v. 6-hourly, to treat seven patients with enteric fever; treatment was continued until 48 hours after defervescence (4–10 days), when pivmecillinam 400 mg orally 6hourly plus probenecid was used to complete a total of 14 days’ chemotherapy. All patients responded initially, but after treatment one patient relapsed 20 days later and only one patient had six sequential negative stool cultures . It was considered that this combination had no advantage over conventional therapy of enteric fever. Some authors treated 12 patients with typhoid by a combination of pivmecillinam and pivampicillin for 10–14 days; all responded to treatment and stool cultures were negative in eight patients who were available for follow-up. In four patients, the S. typhi strain was ampicillin resistant and, as expected, these strains showed relative resistance to mecillinam (MIC 1.3–2.5 mg/ml). Nevertheless, mecillinam and ampicillin were synergistic against these strains in vitro, which was compatible with the clinical outcome . Similarly, 15 enteric fever patients were treated with ﬁxed-dose combination tablets, each containing 100 mg of pivmecillinam and 125 mg of pivampicillin; the dosage was two tablets four times a day, but six patients received i.v. chemotherapy initially . All patients responded satisfactorily, but they were not monitored for persistent fecal excretion of S. typhi. Twelve enteric fever patients were also treated with mecillinam alone; clinical response was satisfactory in only eight. Mecillinam may be suitable for the treatment of septicemias caused by other Salmonella spp. A mecillinam–ampicillin combination was used successfully to control septicemia in a patient with S. enteritidis endocarditis associated with a prosthetic heart valve . Another group treated 12 chronic salmonella carriers (two S. typhi, two S. paratyphi B, and eight other Salmonella spp.), with oral pivmecillinam 300 mg four times daily, for 28 days . The carrier state was eradicated in eight patients, but three of these also had a cholecystectomy. Mecillinam-resistant salmonellae emerged during treatment in the remaining four patients. In another study, a 6-week course of mecillinam eradicated the Salmonella carrier state from one of three long-term Salmonella carriers; a 6-week course of pivmecillinam and pivampicillin (plus oral probenecid in one patient) subsequently eliminated the carrier state in the other two patients .
Other diarrheal illnesses
In one trial, either oral pivmecillinam or oral mecillinam (which is not absorbed) appeared to be equally as effective as co-trimoxazole in adults and children with infections due to Vibrio cholerae and V. parahaemolyticus . Oral pivmecillinam seems comparable to ampicillin for the treatment of shigella dysentery, and it may also prove to be effective for the treatment of this disease caused by ampicillin-resistant strains [31-32]. The combination of pivampicillin and pivmecillinam also eradicates the organism from most Shigella spp. carriers .
Other infections caused by Gram-negative bacilli
Parenterally administered, mecillinam may be suitable for the treatment of septicemias and other systemic infections caused by E. coli and other sensitive Enterobacteriaceae. Addition of mecillinam to cefazolin–carbenicillin for early therapy of septicemia caused by Gram-negative organisms in patients with serious underlying diseases did not improve results of treatment . In a controlled study of infantile gastroenteritis caused by enteropathogenic E. coli, one group received mecillinam, another received co-trimoxazole, and a third group a placebo. Cure rates evaluated clinically on the third day were 79% for mecillinam, 73% for co-trimoxazole, and 7% in control subjects. Organisms were eliminated from the bowel in 53% of patients who received either antibiotic, but from none of those who received a placebo . Some success has been obtained by combining mecillinam with other b-lactam antibiotics, such as carbenicillin, ticarcillin, cephalothin, cefamandole, or cefoxitin, for the treatment of severe infections, such as pyelonephritis, septicemia, and pneumonia caused by Gram-negative bacilli [36-37]. However, a combination of mecillinam plus ticarcillin or carbenicillin was only moderately effective as initial therapy for neutropenic, febrile cancer patients .
An amoxicillin–mecillinam combination
(either amoxicillin 250 mg and pivmecillinam 200 mg or double the dose of both
drugs, three times daily) has been compared with amoxicillin alone, 500 mg three
times daily, in 10-day courses for the treatment of purulent exacerbations of
chronic bronchitis . By the seventh day of treatment, a greater improvement
was noted in patients
Dosage and Administration
For parenteral use, mecillinam hydrochloride dihydrate is available as a powder, containing 82% anhydrous mecillinam, which when dissolved in sterile water is suitable only for i.m. or i.v. administration. This should be administered i.v. in doses of 10 mg/kg (600 mg for adults), as a 15-minute infusion every 4 hours, for the treatment of severe systemic infections. For the treatment of urinary tract infections, 10 mg/kg administered i.v. 6-hourly is sufﬁcient. The i.m. dosage of the drug is the same [41-42]. In clinical trials, somewhat different dosages have been used. Some authors  used 400 mg i.m. or i.v. every 6 hours to treat adults with typhoid fever; Others  prescribed mecillinam 600 mg i.v. 6-hourly for the treatment of Gram-negative septicemias; and as much as 800 mg i.v. 6-hourly in combination with amoxicillin for the initial treatment of typhoid fever, has been used . Pivmecillinam is available in capsules of 150 or 200 mg, each containing 68% anhydrous mecillinam, suitable for oral administration. Depending on the nature and severity of the infection, pivmecillinam can be given in adult doses of 200–400 mg three or four times daily [11, 26, 28-29]. Probenecid, in an adult dose of 1 g daily, can also be administered to augment serum levels, when systemic infections, such as typhoid fever, are treated by oral pivmecillinam .
Newborn infants and children
In young children, 40 mg/kg body weight per day has been given i.m. to treat enteropathogenic E. coli gastroenteritis . In young children, oral pivmecillinam has been used in a dosage of 80 mg/kg/day (twice the parenteral dose), administered in four divided doses, to treat E. coli gastroenteritis .
Impaired renal function
The serum half-life of mecillinam, normally 53 minutes, is prolonged to 334 minutes in patients with severe renal failure. When mecillinam was given in a dosage of 400 mg i.v. 6-hourly for 5 days to patients with severe renal failure, high serum concentrations were attained, but there was no further accumulation of the drug after the ﬁrst few days. Accordingly, it was recommended that mecillinam can be given safely and in normal doses for short-term treatment of patients with renal failure, even when renal function is severely reduced. For long-term treatment, the mecillinam dose should be reduced in patients with severe renal failure . Other authors recommend that the mecillinam dose should always be reduced in patients with severe renal failure [46-47]. In patients receiving treatment by chronic hemodialysis, the rate of removal of mecillinam is such that serum levels remain in the therapeutic range during the procedure. A booster dose of mecillinam is only necessary after dialysis for patients with severe infections. In between dialysis, the intervals between standard doses of the drug should be prolonged to avoid high potentially toxic mecillinam serum levels [47-48].
The adverse effect profile of pivmecillinam is similar to that of other penicillins. The most common side effects of mecillinam use are rash and gastrointestinal upset, including nausea and vomiting.
Prodrugs that release pivalic acid when broken down by the body — such as pivmecillinam, pivampicillin and cefditoren pivoxil — have long been known to deplete levels of carnitine [49-50]. This is not due to the drug itself, but to pivalate, which is mostly removed from the body by forming a conjugate with carnitine. Although short-term use of these drugs can cause a marked decrease in blood levels of carnitine , it is unlikely to be of clinical significance; long-term use, however, appears problematic and is not recommended [52-53].
Maculopapular or urticarial skin rashes appear to be uncommon. Two patients developed erythematous rashes while receiving pivmecillinam, which subsided within a few days after cessation of treatment [8, 54]. No rashes were encountered in several other clinical trials [26, 28, 43]. One patient who developed a skin rash after pivampicillin treatment was treated 2 weeks later by pivmecillinam without recurrence of the rash . Nevertheless, it is wise to assume that mecillinam is cross-allergenic with other penicillins, and to avoid its use in patients with a previous history of penicillin allergy.
The pivaloyl moiety in pivmecillinam
and other drugs with pivaloyl esters binds carnitine through conjugation of
pivalioc acid with carnitine . Carnitine is an essential metabolite in
mitochondral metabolism of fatty acids. The main portion (>95%) of carnitine is
stored in muscular tissues. Carnitine serum levels were found very low after
prolonged treatment with a combination of pivampicillin and pivmecillinam in
children with recurrent urinary tract infections . Only one of these
children had symptoms compatible with mild carnitine deﬁciency.
Mecillinam is not absorbed when given orally. Pivmecillinam is well absorbed after oral administration. The bioavailability increased 20% when pivmecillinam was ingested with or within 1 hour after standard breakfast compared with ingestion 1 hour before a standard breakfast . On doubling the oral pivmecillinam dose, peak serum concentrations increase by approximately 50%, but the area under the curve is doubled. If pivmecillinam is given with food, its bioavailability is much the same . As with other penicillins, concurrent administration of probenecid produces higher and more prolonged mecillinam serum levels .
After a 400-mg dose (equivalent to 273 mg anhydrous mecillinam) to adults, a mean peak serum level of 2.5 mg/ml (expressed as anhydrous mecillinam) is reached approximately 1.5 hours after the dose. Thereafter, the serum level falls, but some mecillinam is still detectable in the serum 6 hours after administration.
The serum half-life is approximately 1 hour [57-58]. Higher serum levels after oral administration have been reported. A mean peak serum level as high as 5 mg/ml was detected after a 400-mg dose in older ambulatory subjects [56, 59]. Older patients are likely to have higher serum concentrations as renal excretion of the drug is slower, and physical activity after antibiotic administration also tends to produce higher serum levels . After i.m. injection of a 335-mg dose of mecillinam hydrochloride dihydrate (equivalent to 273 mg anhydrous mecillinam) to adults, a mean peak serum level of 4.5–5.0 mg/ml (expressed as anhydrous mecillinam) is reached 30–45 minutes later. This peak level is approximately double that attained after an equivalent dose of oral pivmecillinam. Thereafter, the serum level falls more rapidly than that after oral pivmecillinam and the drug cannot be detected in the serum 6 hours after the dose . Doubling the dose, doubles both the peak serum concentration and the area under the curve. If a 10 mg/kg dose (about 600 mg to adults and equivalent to 492 mg anhydrous mecillinam) is administered i.v. as an infusion over 15 minutes, the mean peak serum level, just after the infusion, is approximately 50 mg/ml; this falls to about 13 mg/ml 1 hour after the infusion, and at 4 hours it is 1.0–1.5 mg/ml (anhydrous mecillinam).
When this dose is administered 4-hourly to adults with normal renal
function, there is no accumulation of the drug in the serum. The
serum half-life of mecillinam is approximately 53 minutes [42, 60-61].
Mecillinam penetrates into human CSF in only marginal amounts in
the absence of meningeal inﬂammation, being 1–10% of the
concomitant serum concentration . In
animals, mecillinam is evenly distributed in body ﬂuids and tissue and
produces high concentrations in the kidneys, liver, and lungs, but low
concentrations in the fetus and breast milk . Serum
protein binding of mecillinam is relatively low .
Biliary levels are higher than those in the serum, provided that the biliary
tract is not obstructed. A study investigated 53 patients undergoing biliary
surgery, all of whom received a single i.m.
dose of 800 mg mecillinam 1 hour preoperatively; 11 patients were
Mecillinam is excreted in the urine in an unchanged active form by both glomerular ﬁltration and tubular secretion. Probenecid delays excretion by reducing renal tubular secretion . After i.v. administration, as much as 67% of an administered dose is excreted in urine in the ﬁrst 4 hours; approximately 71% of the dose can be recovered within 24 hours . High urinary concentrations of active mecillinam, up to 3000 mg/ml during times of low urine ﬂow, are attained after an i.v. dose of 10 mg/kg . Unexcreted mecillinam is presumably inactivated in the body, similar to other penicillins. Three antibacterially inactive metabolites of mecillinam have been identiﬁed .
Mechanism of Action
Pivmecillinam interferes with the biosynthesis of the bacterial cell wall however its activity is slightly different from that of other penicillins and cephalosporins.
Mecillinam differs in its antibacterial activity from other penicillins, being much more active against Gram-negative than against Gram-positive organisms [63-65]. As shown in Table 1, it is highly active against most Enterobacteriaceae, such as Escherichia coli, Klebsiella, Salmonella, Shigella, Yersinia, and Citrobacter spp. Proteus mirabilis and P. vulgaris are usually sensitive, but Morganella morganii, Providencia rettgeri, and other Providencia spp. are less often so. Serratia marcescens may be mecillinam sensitive, but most strains are moderately or highly resistant . Pseudomonas aeruginosa, Acinetobacter, and the anaerobic Gram-negative bacilli, such as Bacteroides fragilis, are mecillinam resistant [66-67]. Neisseria spp. are much less sensitive to mecillinam than to ampicillin (Table 1). Gonococci are relatively resistant and b-lactamase-producing strains are completely resistant . Haemophilus inﬂuenzae is moderately resistant and ampicillin resistant strains are highly mecillinam resistant .
Compared with ampicillin, mecillinam’s activity against these organisms is relatively low. All Enterococcus faecalis strains are highly resistant . Staphylococcus saprophyticus is relatively resistant, but sufﬁciently high concentrations may be attained in the urine to inhibit this bacterium [13, 69].
Table 1. In vitro susceptibility of mecillinam compared to ampicillin.
Emerging resistance and cross-resistance
Bacteria exhibiting cross-resistance
between ampicillin and mecillinam are usually those which produce large amounts
of b-lactamases. Although mecillinam can be
inactivated by b-lactamases, it is generally more
stable than ampicillin because of its relatively low afﬁnity for them. The two
drugs may also differ in their sensitivity to the various types of
b-lactamases produced by individual organisms.
Another reason why Enterobacteriaceae are more sensitive to mecillinam than to
ampicillin is mecillinam’s superior ability to penetrate through the outer
layers of the bacterial cell envelope [64, 72]. Mecillinam-resistant strains of
many bacterial species can be readily selected in vitro by repeated
passage in the presence of the antibiotic [2, 64]. Emergence of resistant
strains was not a major problem when the drug was used to treat urinary tract
infections [9, 12, 73]. It appears that short courses of treatment are unlikely
to select resistant fecal organisms and lead to therapeutic failure .
Mecillinam-resistant variants can sometimes be demonstrated in urine containing
therapeutic concentrations of the drug. The generation time of these resistant
strains is 3.0–4.5 times as long as that of susceptible organisms, which may be
why such resistant organisms do not usually colonize the urinary tract during
chemotherapy . Mecillinam-resistant strains have emerged during treatment of
other infections, including those due to Salmonella spp. , E. coli
, and K. pneumoniae . These mecillinam-resistant variants
were spherical in shape, and most of them were unstable and readily
reverted to their mecillinam-sensitive rod-shaped form. Stable
mutants of K. pneumoniae and E. coli were also detected, which were
identical to the unstable variants with regard to form, growth rate, and
sensitivity to mecillinam.
Amongst Enterobacteriaceae isolated from patients in the community
and hospitals, resistance to mecillinam is much less common than
to ampicillin [73, 77-78]. Most ampicillin-resistant Enterobacteriaceae isolated from fecal
ﬂora or infected urines are mecillinam sensitive. This seems to include
Other pharmacological effects
The key pharmacokinetic and pharmacodynamic parameters that are linked to clinical efﬁcacy are not known, but presumably are similar to other b-lactams – namely, time above the MIC. Mecillinam alone has a prolonged (>3 hours) post-antibiotic effect on E. coli. The combinations of mecillinam with ampicillin, aztreonam, ceftazidime, or piperacillin at most concentrations induce longer postantibiotic effect (PAEs) on E. coli than do the sum of the individual antibiotic PAEs. Thus, there is a synergistic PAE on Gram-negative bacteria when mecillinam is combined with these other antibiotics .
CAS number: 32887-01-7 EINECS: 251-276-6
1. Lund F., Tybring L. "6-beta-amidinopenicillanic acids – a new group of antibiotics". Nature New Biol. 236: 135, (1972).
2. Matsuhashi S., Kamiryo T., Blumberg P.M. et al. "Mechanism of action and development of resistance to a new amidino penicillin". J. Bacteriol. 117: 578, (1974).
3. Nicolle L.E., "Pivmecillinam in the treatment of urinary tract infections". J. Antimicrob. Chemother. 46 (Suppl A): 35–39, (2000).
4. Graninger W., "Pivmecillinam—therapy of choice for urinary tract infection". Int. J. Antimicrob. Agents 22 Suppl 2: 73–8, (2003).
5. Tanphaichitra D., Srimuang S., Chiaprasittigul P., Menday P., Christensen O.E., "The combination of pivmecillinam and pivampicillin in the treatment of enteric fever". Infection 12 (6): 381–3, (1984).
6. Pham P., Bartlett J.G., "Amdinocillin (Mecillinam)". Point-of-Care Information Technology ABX Guide. Johns Hopkins University, (2008).
7. Bentzen A.J., Vejlsgaard R., Jacobsen J., Tybring L. "Clinical evaluation of a novel beta-lactam antibiotic: Pivmecillinam (FL 1039)". Infection 3: 154, (1975).
8. Verrier Jones E.R., Asscher A.W. "Treatment of recurrent bacteriuria with pivmecillinam (FL 1039)". J. Antimicrob. Chemother. 1: 193, (1975).
9. Damsgaard T., Jacobsen J., Korner B., Tybring L. "Pivmecillinam and trimethoprim/sulfamethoxazole in the treatment of bacteriuria". J. Antimicrob. Chemother. 5: 267, (1979).
10. Cox C.E. "Parenteral amdinocillin for treatment of complicated urinary tract infections". Am. J. Med. 75: 82, (1983).
11. Sanderson P., Menday P. "Pivmecillinam for bacteriuria in pregnancy". J. Antimicrob. Chemother. 13: 383, (1984).
12. Aaraas I., Skarsten K.W., Neess H.C. "Pivmecillinam in the treatment of post-operative bacteriuria in gynecological patients. A double-blind comparison with pivmecillinam and pivampicillin". J. Antimicrob. Chemother. 3: 227, (1977).
13. Anderson J.D., Adams M.A., Wilson L.C., Shepherd C.A. "Studies on the effect of mecillinam upon micrococcaceae and faecal streptococci under conditions simulating urinary tract infection". J. Antimicrob. Chemother. 2: 351, (1976).
14. Granlund M., Landgren E., Henning C. "Pivmecillinam in treatment of Staphylococcus saprophyticus urinary tract infections". Scand. J. Infect. Dis. 15: 65, (1983).
15. Igesund A., Vorland L. "A ﬁxed combination of pivmecillinam and pivampicillin in complicated urinary tract infections. A double-blind comparison with pivmecillinam". Scand. J. Infect. Dis. 14: 159, (1982).
16. Multicenter Study from Medical, Surgical and Bacteriological Departments at Danish Hospitals and the State Serum Institute, Copenhagen, Denmark. "A ﬁxed combination of pivmecillinam and pivampicillin in complicated urinary tract infections". Scand. J. Infect. Dis. 15: 195, (1983).
17. Eriksson S., Zbornick J., Dahnsjo H. et al. "The combination of pivampicillin and pivmecillinam versus pivampicillin alone in the treatment of acute pyelonephritis". Scand. J. Infect. Dis. 18: 431, (1986).
18. Ward T.T., Amon M.B., Krause L.K. "Combination of amdinocillin and cefoxitin therapy of multiply-resistant Serratia marcescens urinary tract infections". Am. J. Med. 75: 85, (1983).
19. Jodal U., Larsson P., Hansson S., Bauer C. -A. "Pivmecillinam in long-term prophylaxis to girls with recurrent urinary tract infection". Scand. J. Infect. Dis. 21: 299, (1989).
20. Greenwood D. "Effect of osmolality on the response of Escherichia coli to mecillinam". Antimicrob. Agents Chemother. 10: 824, (1976).
21. Ball A.P., Farrell I.D., Gillett A.P. et al. "Enteric fever in Birmingham: Clinical features, laboratory investigation and comparison of treatment with pivmecillinam and co-trimoxazole". J. Infect: 1: 353, (1979).
22. Mandal B.K., Ironside A.G., Brennand J. "Mecillinam in enteric fever". Br. Med. J. 1: 586, (1979).
23. Jones D.A., Kudlac H., Edwards I.R. "Pivmecillinam and relapse of typhoid fever". J. Infect. Dis. 145: 773, (1982).
24. McKendrick M.W., Geddes A.M. "Mecillinam and amoxycillin in enteric fever". J. Antimicrob. Chemother. 5: 727, (1979).
25. Tanphaichitra D., Bussayanond A., Christensen O. "The combination of pivmecillinam and pivampicillin in the treatment of acute enteric fever". J. Antimicrob. Chemother. 8: 23, (1981).
26. Limson B.M., Mendoza M.T., Liwanag E. et al. "Randomised, comparative trial of mecillinam, mecillinam/ampicillin and chloramphenicol in the treatment of enteric fever". J. Antimicrob. Chemother. 9: 405, (1982).
27. Shanson D.C., Brigden W., Weaver E.J.M. "Salmonella enteritidis endocarditis". Br. Med. J. 1: 612, (1977).
28. Jonsson M., Tunevall G. "FL 1039: A new beta-lactam derivative for the treatment of infections with Gram-negative bacteria". Infection 3: 31, (1975).
29. Bruun J.N., Digranes A., Bře J., Maeland A. "Treatment of Salmonella carriers with pivmecillinam alone or in combination with pivampicillin: Experience with three patients". Scand. J. Infect. Dis. 15: 21, (1983).
30. Uylangco C., Santiago L., Pescante M. et al. "Pivmecillinam, cotrimoxazole and oral mecillinam in gastroenteritis due to Vibrio spp.". J. Antimicrob. Chemother. 13: 171, (1984).
31. Kabir I., Rahaman M.M., Ahmed S.M. et al. "Comparative efﬁcacies of pivmecillinam and ampicillinam in acute shigellosis". Antimicrob. Agents Chemother. 25: 643, (1984).
32. Prado D., Liu H., Velasquez T., Cleary T.G. "Comparative efﬁcacy of pivmecillinam and cotrimoxazole in acute shigellosis in children". Scand. J. Infect. Dis. 25: 713, (1993).
33. Ekwall E., Svenungsson B. "Pivampicillin/pivmecillinam in the treatment of Shigella carriers". Scand. J. Infect. Dis. 22: 623, (1990).
34. Klastersky J., Coppens L., Meunier-Carpentier F., Menday A.P. "Carbenicillin plus cefazolin with or without mecillinam as an early treatment of bacteremia caused by Gram-negative organisms: Randomized double blind study". Antimicrob. Agents Chemother. 18: 437, (1980).
35. Thorén A., Wolde-Mariam T., Stintzing G. et al. "Antibiotics in the treatment of gastro-enteritis caused by enteropathogenic Escherichia coli". J. Infect. Dis. 141: 27, (1980).
36. King J.W., Beam Jr T.R., Neu H.C., Smith L.G. "Systemic infections treated with amdinocillin in combination with other beta-lactam antibiotics". Am. J. Med. 75: 90, (1983).
37. Rotstein C., Farrar Jr W.E. "Amdinocillin in combination with beta-lactam antibiotics for treatment of serious Gram-negative infections". Am. J. Med. 75: 96, (1983).
38. Lawson R.D., Estey E.H., Bodey G.P. "Amdinocillin: Use alone or in combination with cefoxitin or carbenicillin-ticarcillin". Am. J. Med. 75: 113, (1983).
39. Pines A., Nandi A.R., Raafat H., Rahman M. "Pivmecillinam and amoxycillin as combined treatment in purulent exacerbations of chronic bronchitis". J. Antimicrob. Chemother. 3 (Suppl B): 141, (1977).
40. Lal S., McGhie D., Kerfoot P. "A comparison of pivmecillinam/pivampicillin and co-trimoxazole in hospitalized patients with acute exacerbations of chronic bronchitis". J. Antimicrob. Chemother. 14: 179, (1984).
41. Gambertoglio J.G., Barriere S.L., Lin E.T., Conte Jr J.E. "Amdinocillin pharmacokinetics. Simultaneous administration with cephalothin and cerebrospinal ﬂuid penetration". Am. J. Med. 75: 54, (1983).
42. Barriere S.L., Gambertoglio J.G., Lin E.T., Conte Jr J.E. "Multiple-dose pharmacokinetics of amdinocillin in healthy volunteers". Antimicrob. Agents Chemother. 21: 54, (1982).
43. Clarke P.D., Geddes A.M., McGhie D., Wall J.C. "Mecillinam: A new antibiotic for enteric fever". Br. Med. J. 2: 14, (1976).
44. McKendrick M.W., Geddes A.M. "Mecillinam and amoxycillin in enteric fever". J. Antimicrob. Chemother. 5: 727, (1979).
45. Svarva P.L., Wessel-Aas T. "Serum levels of mecillinam in patients with severely impaired renal function". Scand. J. Infect. Dis. 12: 303, (1980).
46. Ekberg M., Denneberg T., Larsson S., Juhlin I. "Pharmacokinetic and therapeutic studies of pivmecillinam in patients with normal and impaired renal function". Scand. J. Infect. Dis. 10: 127, (1978).
47. Bailey K., Cruickshank J.G., Bisson P.G., Radford B.L. "Mecillinam in patients on haemodialysis". Br. J. Clin. Pharmacol. 10: 177, (1980).
48. Patel I.H., Bornemann L-D., Brocks V.M. et al. "Pharmacokinetics of intravenous amdinocillin in healthy subjects and patients with renal insufﬁciency". Antimicrob. Agents Chemother. 28: 46, (1985).
49.Holme E., Greter J., Jacobson C.E., et al., "Carnitine deficiency induced by pivampicillin and pivmecillinam therapy". Lancet 2 (8661): 469–73, (1989).
50. Brass E.P., "Pivalate-generating prodrugs and carnitine homeostasis in man". Pharmacol. Rev. 54 (4): 589–98, (2002).
51. Abrahamsson K., Holme E., Jodal U., Lindstedt S., Nordin I., "Effect of short-term treatment with pivalic acid containing antibiotics on serum carnitine concentration—a risk irrespective of age". Biochem. Mol. Med. 55 (1): 77–9, (1995).
52. Holme E., Jodal U., Linstedt S., Nordin I., "Effects of pivalic acid-containing prodrugs on carnitine homeostasis and on response to fasting in children". Scand. J. Clin. Lab. Invest. 52 (5): 361–72, (1992).
53. Makino Y., Sugiura T., Ito T., Sugiyama N., Koyama N., "Carnitine-associated encephalopathy caused by long-term treatment with an antibiotic containing pivalic acid". Pediatrics 120 (3): e739–41, (2007).
54. Bresky B. "Controlled randomized study comparing amoxycillin and pivmecillinam in adult out-patients presenting with symptoms of acute urinary tract infection". J. Antimicrob. Chemother. 3 (Suppl B): 121, (1977).
55. Bornemann L.D., Castellano S., Lin A.H. et al. "Inﬂuence of food on bioavailability of amdinocillin pivoxil". Antimicrob. Agents Chemother. 32: 592, (1988).
56. Roholt K. "Pharmacokinetic studies with mecillinam and pivmecillinam". J- Antimicrob. Chemother. 3 (Suppl B): 71, (1977).
57. Williams J.D., Andrews J., Mitchard M., Kendall M.J. "Bacteriology and pharmacokinetics of the new amidinopenicillin-mecillinam". J. Antimicrob. Chemother. 2: 61, (1976).
58. Mitchard M., Andrews J., Kendall M.J., Wise R. "Mecillinam serum levels following intravenous injection: A comparison with pivmecillinam". J. Antimicrob. Chemother. 3 (Suppl. B): 83, (1977).
59. Roholt K., Nielsen B., Kristensen E. "Pharmacokinetic studies with mecillinam and pivmecillinam". Chemotherapy 21: 146, (1975).
60. Gambertoglio J.G., Barriere S.L., Lin E.T., Conte Jr J.E. "Pharmacokinetics of mecillinam in healthy subjects". Antimicrob. Agents Chemother. 18: 952, (1980).
61. Meyers B.R., Jacobson J., Masci J. et al. "Pharmacokinetics of amdinocillin in healthy adults". Antimicrob. Agents Chemother. 23: 827, (1983).
62. Hares M.M., Hegarty A., Tomkyns J. et al. "A study of the biliary excretion of mecillinam in patients with biliary disease". J. Antimicrob. Chemother. 9: 217, (1982).
63. Reeves D.S., Wise R., Bywater M.J. "A laboratory evaluation of a novel beta-lactam antibiotic mecillinam". J. Antimicrob. Chemother. 1: 337, (1975).
64. Tybring L. "Mecillinam (FL 1060), a 6-beta-amidinopenicillanic acid derivative. In vitro evaluation". Antimicrob. Agents Chemother. 8: 266, (1975).
65. Neu H.C. "Mecillinam, a novel penicillanic acid derivative with unusual activity against Gram-negative bacteria". Antimicrob. Agents Chemother. 9: 793, (1976).
66. Trestman I., Kaye D., Levison M.E. "Activity of semisynthetic penicillins and synergism with mecillinam against Bacteroides species". Antimicrob. Agents Chemother. 16: 283, (1979).
67. Steinkraus G.E., McCarthy L.R. "In vitro activity of mecillinam against anaerobic bacteria". Antimicrob. Agents Chemother. 17: 954, (1980).
68. Khan M.Y., Siddiqui Y., Gruninger R.P. "Comparative in-vitro activity of selected new beta-lactam antimicrobials against Neisseria gonorrhoeae". Br. J. Vener. Dis. 58: 228, (1982).
69. Hovelius B, Mĺrdh P.-A. "Staphylococcus saprophyticus as a common cause of urinary tract infection". Rev. Infect. Dis. 6: 328, (1984).
70. Hammerschlag M.R., Gleyzer A. "In vitro activity of a group of broad spectrum cephalosporins and other beta-lactam antibiotics against Chlamydia trachomatis". Antimicrob. Agents Chemother. 23: 493, (1983).
71. Bostock J.M., Geary I., Eley A., Chopra I. "Mecillinam has potent in vitro activity against Chalydia pneumoniae ATCC VR1310". J. Antimicrob. Chemother. 53: 1112, (2004).
72. Richmond M.H. "In vitro studies with mecillinam on Escherichia coli and Pseudomonas aeruginosa". J. Antimicrob. Chemother. 3, (Suppl B): 29, (1977).
73. Kahlmeter G. "An international survey of the animicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO-SENS project". J. Antimicrob. Chemother. 58: 69, (2003).
74. Anderson J.D., Adams M.A., Webster H.M., Smith L. "Growth properties of mecillinam-resistant bacterial variants in urine". Antimicrob. Agents Chemother. 12: 559, (1977).
75. Barbour A.G., Mayer L.W.,
Spratt B.G. "Mecillinam resistance in Escherichia coli: dissociation of
growth inhibition and morphologic change". J. Infect. Dis.
76. Van der Voet G.B., Mattie H., Van Furth R. "Comparison of in vitro and in vivo ampicillin susceptibility of Escherichia coli pretreated with low concentrations of mecillinam and ampicillin". Scand. J. Infect. Dis. 15: 97, (1982).
77. Anderson J.D., Adams M.A., Barrington J.C. et al. "Comparison of the epidemiology of bacterial resistance to mecillinam and ampicillin". Antimicrob. Agents Chemother. 10: 872,(1976).
78. Hassam Z. "Sensitivity of urinary-tract isolates to mecillinam and amoxycillin". Lancet 1: 445, (1978).
79. Thomas K., Weinbren M.J., Warner M., Woodford N., Livermore D. "Activity of mecillinam against ESBL producers in vitro". J. Antimicrob. Chemother. 57: 367, (2006).
80. Hansson H.B., Walder M., Juhlin I. "Susceptibility of shigellae to mecillinam, nalidixic acid, trimethoprim, and ﬁve other antimicrobial agents". Antimicrob. Agents Chemother. 19: 271, (1981).
81. Juhlin I., Winblad S. "Susceptibility to mecillinam and other anitbiotics of 28 O-serotypes of Yersinia enterocolitica". J. Antimicrob. Chemother. 8: 291, (1981).
82. Greenwood D., Brooks H.L., Gargan R., O’Grady F. "Activity of FL 1060, a new beta-lactam antibiotic, against urinary tract pathogens". J. Clin. Path. 27: 192, (1974).
83. Uwaydah M., Osseiran M. "Susceptibility of recent Shigella isolates to mecillinam, ampicillin, tetracycline, chloramphenicol and cotrimoxazole". J. Antimicrob. Chemother. 7: 619, (1981).
84. Haider K., Albert M.J., Nahar S., Kibriya A.KM.G. "Plasmid-associated resistance to pivmecillinam in Shigella ﬂexneri and Shigella boydii". J. Antimicrob. Chemother. 28: 599, (1991).
85. Haider K., Malek M.A., Albert M.J. "Occurrence of drug resistance in Shigella species isolated from patients with diarrhoea in Bangladesh". J. Antimicrob. Chemother. 32: 509, (1993).
86. Tybring L., Melchior N.H. "Mecillinam (FL 1060), a 6-beta amidinopenicillanic acid derivative: Bactericidal action and synergy in vitro". Antimicrob. Agents Chemother. 8: 271, (1975).
87. Hanberger H., Nilsson
L.E., Svensson E., Maller R. "Synergistic postantiotic effect of mecillinam in
combination with other beta-lactam antibiotics inrelation to morphology and
initialkilling". J. Antimicrob. Chemother. 28: 523, (1993).
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