Eleven countries in LATAM (20 laboratory sampling sites having 93–503 organism samples/site) were sampled with a target of ≥250 isolates per nation. These institutions were generally tertiary-care hospitals. The compliance to protocol ranged from 190 [Venezuela, 95%] to >100% for the “developed” countries. The collected organisms were isolated consecutively from various types of clinical infections (prevalence design) including bloodstream (18.8%), respiratory tract (20.1%), skin and skin structure (13.1%) as well as other or unspecified body sites. The countries (sites; sample size) were: Argentina (two; 498), Brazil (five; 1588), Chile (two; 467), Colombia (one; 208), Costa Rica (one; 193), Ecuador (one; 192), Guatemala (one; 201), Mexico (three, 1052), Panama (one; 196), Peru (one; 194) and Venezuela (two, 190); one isolate per patient per infectious episode, see Table 1. The organisms forwarded to the monitoring central laboratory (JMI Laboratories) were as follows: S. aureus (921), coagulase-negative Staphylococcus species (CoNS; 299), enterococci (218; 92.2% E. faecalis or E. faecium), S. pneumoniae (182), β-haemolytic streptococci (115; 92.2% S. pyogenes or S. agalactiae), viridans group streptococci (90; more than eight species), E. coli (644; 37.3% ESBL phenotype), Klebsiella spp. (517; three species, 52.4% ESBL phenotype), Enterobacter spp. (272), P. mirabilis (74; 24.3% ESBL phenotype), other Enterobacteriaceae (292), H. influenzae (128; 29.7% β-lactamase-positive), M. catarrhalis (33), P. aeruginosa (586), and Acinetobacter spp. (494; 94.7% A. baumannii). A total of 4979 isolates were tested, 4865 or 97.7% of which are presented in Tables 2 and 3; the remaining organisms occurred in small numbers precluding a significant sample size per species, e.g. limited analytical power.

Organisms detected with resistances to key, available agents were tested by various molecular methods such as PCR amplification/sequencing, example ESBLs, MBLs, MDR Gram-negative bacilli or Gram-positive cocci.1,2

CLSI M07-A9 (2012) methods were applied using validated broth microdilution panels produced by ThermoFisher Scientific Inc., formerly TREK Diagnostics (Cleveland, Ohio, USA).8 Interpretations of results utilized CLSI (M100-S23, 2013), USA-Food and Drug Administration (FDA) and EUCAST (2013) criteria;9–11 and the results of quality control (QC) tests were dominantly (nearly 99.0%) within QC ranges (CLSI M100-S23) for six utilized control organisms.

The sponsor's (Pfizer Inc., New York, New York, USA) compounds included: linezolid, tigecycline, piperacillin/tazobactam, ampicillin/sulbactam, cefoperazone and cefoperazone/sulbactam. For studying Gram-negative bacilli, Gram-positive cocci, and fastidious respiratory tract species, numerous additional (15–25) drugs were also tested. ESBL patterns were defined for E. coli, Klebsiella spp. and Proteus mirabilis per CLSI (2013) criteria as a MIC of ≥2mg/L for aztreonam or ceftriaxone or ceftazidime.9,10 Carbapenem-resistant Enterobacteriaceae (CRE) were detected by a MIC at ≥2mg/L for doripenem or imipenem or meropenem.9

S. aureus isolates (921, 47.8% MRSA overall) exhibited complete (100.0%) susceptibility to linezolid (MIC50/90, 1/2mg/L), daptomycin (MIC50/90, 0.25/0.5mg/L), tigecycline (MIC50/90, 0.06/0.12mg/L) and vancomycin (MIC50/90, 1/1mg/L). Rare (1.1%) resistance to trimethoprim/sulfamethoxazole (TMP/SMX) was observed (Table 2). Aminoglycoside (gentamicin) resistance was approximately 20.0% with higher rates documented in Peru (72.2%), Chile (30.0%), Argentina (30.7%) and Venezuela (30.6%).

CoNS samples (299; 83.9% methicillin-resistant) showed common co-resistances and only four agents with >90% susceptibility rates including linezolid, daptomycin, doxycycline, and vancomycin (94.3–100.0% susceptible). The rare occurrences of linezolid non-susceptibility (1.7%) occurred in Brazil (five strains [4.8%]; three species [S. epidermidis, three clonal isolates with a G2576 mutation; one S. hominis with a G2576, L3 at F1475 and M156T, and L4 at 577T mutations and one S. lugdunensis with a G2576 mutation]) with MIC values of 8–32mg/L; and Mexico (two strains of S. epidermidis and S. haemolyticus having cfr±L3 or L4 mutations) with MIC values at only 4mg/L. Teicoplanin non-susceptible results (11.4% by EUCAST breakpoints) were found in Brazil (10 strains, 9.6%), Costa Rica (six strains, 42.9%), Mexico (eight strains, 8.9%), Panama (two strains, 15.4%), Peru (two strains, 14.3%), and Venezuela (five strains, 45.5%).

Enterococci (218, either E. faecalis or E. faecium) had a VRE rate of 14.2–15.1% and 91.4–93.7% with a VAN-A pattern (Tables 1 and 2). Ten nations had documented VRE (range, 7.1% [Costa Rica] to 25.7–26.5% [Brazil and Mexico]), and the best tested agents (% susceptible) were linezolid (98.6%), daptomycin (100.0%), teicoplanin (86.2–86.7%) and vancomycin (84.9%). Linezolid non-susceptibility was detected in Brazil (2.9% prevalence overall; G2576 mutations in a clonal E. faecalis) and in Panama City, Panama (13.3% prevalence; cfr clonal occurrences in E. faecalis).

S. pneumoniae (182) isolates from LATAM were dominantly penicillin-non-susceptible (51.6%; using CLSI non-meningitis breakpoints) with highest rates observed in Mexico (84.8%) and Venezuela (81.2%). Similarly, ceftriaxone non-susceptible rates were elevated (21.1–43.7%) in the same two nations. Poor coverage (low susceptible %) were noted for erythromycin (62.6%), tetracycline (63.7–64.8%) and TMP/SMX (45.1–48.4%). The best antimicrobials tested against pneumococci were levofloxacin, linezolid, tigecycline and vancomycin, each inhibiting all strains at published breakpoints (Table 2). For other streptococci, important resistance profiles observed were: (1) 13.9 and 56.5% non-susceptible for macrolides and tetracyclines in β-haemolytic streptococci, respectively, (2) ≥91.1% susceptible rates for all drugs except penicillin (58.9%, CLSI criteria), erythromycin (50.0%) and tetracycline (61.1%) in viridans group streptococci, and (3) rare daptomycin (1.1%) and fluoroquinolone non-susceptible (1.7–3.3%) rates were observed (Table 2).

E. coli (644) had an ESBL-phenotype rate of 37.3%, see Table 4. The most active tested agents were amikacin (92.7% susceptible), cefoperazone/sulbactam (92.7%), meropenem (100.0%) and tigecycline (100.0%). The most active cephalosporin against E. coli was cefepime at 72.4% by CLSI breakpoints (Table 3). Klebsiella spp. (517) showed very elevated resistance rates (Table 3), with only four drugs inhibiting ≥80.0% of isolates (tigecycline [97.9%], colistin [96.5%], meropenem [90.3%] and amikacin [89.0%]). The ESBL phenotype rate was 52.4% (Table 4), and CRE were identified (no./percentage) in Argentina (6/10.7), Brazil (31/17.3), Colombia (4/18.2), Ecuador (2/10.0), Mexico (1/1.1), Panama (4/20.0) and Venezuela (3/15.0). The following carbapenemases were identified: KPC-2 (Brazil,3 Ecuador,2 Venezuela3), KPC-3 (Colombia,2 Panama3) and NDM-1 (Colombia1). P. mirabilis (74) showed an ESBL-phenotype rate at 24.3% and several UTI-targeted antimicrobials (ampicillin and TMP/SMX) were only 47.3–52.7% effective in vitro.

Among other enteric bacilli, Enterobacter spp. showed a CRE rate at 2.9% with higher rates in Colombia and Venezuela (10.0–12.5%). Amikacin, cefoperazone/sulbactam, cefepime, carbapenems and tigecycline were quite active against these species, as were nearly all tested agents versus H. influenzae (128) and M. catarrhalis (33); see Table 3.

P. aeruginosa (586) were most susceptible to amikacin (75.4%), tobramycin (70.1%) and colistin (99.5%; Table 3). Carbapenem resistance was high due to endemic β-lactamase (SPM-1, usually in Brazil), but the most elevated rates were noted in Guatemala (75.8%), Peru (62.5–68.8%) and Ecuador (55.6%). The most active β-lactam was ceftazidime (65.7%, MIC50 at 4mg/L). Acinetobacter spp. (494, four species) were significantly inhibited (% susceptible) only by colistin (98.6%), cefoperazone/sulbactam (59.3%), doxycycline (80.4%) and tigecycline (MIC90, 4mg/L). All carbapenems, aminoglycosides and ampicillin/sulbactam showed susceptibility rates at <50%, many <20%; see Table 3.

Monitoring of nearly 5000 LATAM pathogens in 2011 documents increasing antimicrobial resistances among nearly all sampled species (Tables 1–3), confirming earlier reports.1,3,6 Although methicillin resistance was elevated among staphylococci (47.8–83.9%), several agents (daptomycin, glycopeptides, linezolid and tigecycline) retained potent activity in LATAM like elsewhere in the world.4–7 VRE appears to be expanding (14.2–15.1%, in 10 nations) as are non-susceptible rates for β-lactams in S. pneumoniae. In contrast, USA rates of VRE particularly among bacteremia isolates of E. faecium have escalated to more than 80%,12 and ceftriaxone non-susceptible rates were at 12.5% in 2009 samples of pneumococci.13 Rare linezolid-resistant (<1.0% overall) CoNS and enterococci were noted with cfr and target site mutations, as previously noted in Mexico.6

β-Lactamase-mediated (ESBL, MBL [NDM-1], Class A and D carbapenamases) resistance in E. coli, Klebsiella spp., some other Enterobacteriaceae, and non-fermentative bacilli continues to evolve (Table 3) to levels of 37.3–52.4% and few drugs have ≥90.0% level inhibition at published breakpoints.1–4,14 This demands routine use of combination empiric therapies directed by surveillance programs and patient isolate tests for LATAM patients; and interventions will be required to control further resistance escalation in this geographic region.